[hsCRP protein in children and adolescents with diabetes type 1].

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Głowińska-Olszewska, Barbara; Urban, Mirosława; Peczyńska, Jadwiga; Koput, Alicja

2007-01-01

HsCRP protein is known as a novel marker of low grade inflammatory state, which characterises an atherosclerotic process in its early stages. Contrary to a large amount of data on inflammatory markers in diabetes type 2 and metabolic syndrome in adults, little is known so far about the inflammatory process in diabetes type 1, especially in children. The aim of the study was to estimate the level of hsCRP protein in children and adolescents with diabetes type 1 depending on coexisting additional risk factors for atherosclerosis and microvascular complications. 127 children and adolescents with diabetes duration 6.7+/-3.3 years, aged 14.9+/-3.1, were studied. The control group consisted of 52 healthy children aged 14.9+/-2.8 years, matched acc. to gender. HsCRP level was assessed with use of immunoturbidymetric, latex augmented method (Tina-quant CRP (Latex) HS, Roche). HsCRP in the whole study group was nearly significantly higher compared to control group: 0.17+/-0.2 vs. 0.078+/-0.1 mg/dl, p=0.072. In diabetic hypertensive children (n=38) we found significantly higher levels of hsCRP compared to controls (0.27+/-0.3 vs. 0.07 mg/dl, p=0.008) and compared to diabetic normotensive children (0.13+/-0.22 mg/dl; p=0.024). Diabetic obese patients (n=23) had significantly higer hsCRP compared to controls (0.24+/-0.3 vs. 0.07+/-0.1 mg/dl, p=0.04). In 14 studied diabetic children we found coexisting hypertension and obesity, and we found further increase in hsCRP level - 0.28+/-0.3 mg/dl. In diabetic children with microangiopathy hsCRP level was 0.22+/-0.2 mg/dl, and it was insignificantly higher compared to controls and to diabetic children without complications. Correlation analysis showed interrelations between hsCRP and systolic blood pressure (r=0.2; p=0.04) and HbA1c (r=0.25; p=0.015). In stepwise regression analysis hsCRP was related to systolic blood pressure, HbA1c and the triglycerides level (R=0.37; p=0.003). In children and adolescents with diabetes type 1 we

Fnr is involved in oxygen control of Herbaspirillum seropedicae N-truncated NifA protein activity in Escherichia coli.

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Monteiro, Rose A; de Souza, Emanuel M; Yates, M Geoffrey; Pedrosa, Fabio O; Chubatsu, Leda S

2003-03-01

Herbaspirillum seropedicae is an endophytic diazotroph belonging to the beta-subclass of the class Proteobacteria, which colonizes many members of the Gramineae. The activity of the NifA protein, a transcriptional activator of nif genes in H. seropedicae, is controlled by ammonium ions through its N-terminal domain and by oxygen through mechanisms that are not well understood. Here we report that the NifA protein of H. seropedicae is inactive and more susceptible to degradation in an fnr Escherichia coli background. Both effects correlate with oxygen exposure and iron deprivation. Our results suggest that the oxygen sensitivity and iron requirement for H. seropedicae NifA activity involve the Fnr protein.

The global nitrogen regulator, FNR1, regulates fungal nutrition-genes and fitness during Fusarium oxysporum pathogenesis.

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Divon, Hege Hvattum; Ziv, Carmit; Davydov, Olga; Yarden, Oded; Fluhr, Robert

2006-11-01

SUMMARY Fusarium oxysporum is a soil-borne pathogen that infects plants through the roots and uses the vascular system for host ingress. Specialized for this route of infection, F. oxysporum is able to adapt to the scarce nutrient environment in the xylem vessels. Here we report the cloning of the F. oxysporum global nitrogen regulator, Fnr1, and show that it is one of the determinants for fungal fitness during in planta growth. The Fnr1 gene has a single conserved GATA-type zinc finger domain and is 96% and 48% identical to AREA-GF from Gibberella fujikuroi, and NIT2 from Neurospora crassa, respectively. Fnr1 cDNA, expressed under a constitutive promoter, was able to complement functionally an N. crassa nit-2(RIP) mutant, restoring the ability of the mutant to utilize nitrate. Fnr1 disruption mutants showed high tolerance to chlorate and reduced ability to utilize several secondary nitrogen sources such as amino acids, hypoxanthine and uric acid, whereas growth on favourable nitrogen sources was not affected. Fnr1 disruption also abolished in vitro expression of nutrition genes, normally induced during the early phase of infection. In an infection assay on tomato seedlings, infection rate of disruption mutants was significantly delayed in comparison with the parental strain. Our results indicate that FNR1 mediates adaptation to nitrogen-poor conditions in planta through the regulation of secondary nitrogen acquisition, and as such acts as a determinant for fungal fitness during infection.

Transcriptional regulation of the outer membrane porin gene ompW reveals its physiological role during the transition from the aerobic to the anaerobic lifestyle of Escherichia coli

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Minfeng eXiao

2016-05-01

Full Text Available Understanding bacterial physiology relies on elucidating the regulatory mechanisms and cellular functions of those differentially expressed genes in response to environmental changes. A widespread Gram-negative bacterial outer membrane protein OmpW has been implicated in the adaptation to stresses in various species. It is recently found to be present in the regulon of the global anaerobic transcription factor FNR and ArcA in E. coli. However, little is known about the physiological implications of this regulatory disposition. In this study, we demonstrate that transcription of ompW is indeed mediated by a series of global regulators involved in the anaerobiosis of E. coli. We show that FNR can both activate and repress the expression of ompW through its direct binding to two distinctive sites, -81.5 and -126.5 bp respectively, on ompW promoter. ArcA also participates in repression of ompW under anaerobic condition, but in an FNR dependent manner. Additionally, ompW is also subject to the regulation by CRP and NarL which senses the availability and types of carbon sources and respiration electron acceptors in the environment respectively, implying a role of OmpW in the carbon and energy metabolism of E. coli during its anaerobic adaptation. Molecular docking reveals that OmpW can bind fumarate, an alternative electron acceptor in anaerobic respiration, with sufficient affinity. Moreover, supplement of fumarate or succinate which belongs to the C4-dicarboxylates family of metabolite, to E. coli culture rescues OmpW-mediated colicin S4 killing. Taken together, we propose that OmpW is involved in anaerobic carbon and energy metabolism to mediate the transition from aerobic to anaerobic lifestyle in E. coli.

Core physics analysis in support of the FNR HEU-LEU demonstration experiment

Energy Technology Data Exchange (ETDEWEB)

Losey, David C; Brown, Forrest B; Martin, William R; Lee, John C [Department of Nuclear Engineering, University of Michigan (United States)

1983-08-01

A core neutronics analysis has been undertaken to assess the impact of low-enrichment fuel on the performance and utilization of the FNR As part of this analytic effort a computer code system has been assembled which will be of general use in analyzing research reactors with MTR-type fuel. The code system has been extensively tested and verified in calculations for the present high enrichment core. The analysis presented here compares the high-and-low enrichment fuels in batch and equilibrium core configurations which model the actual FNR operating conditions. The two fuels are compared for cycle length, fuel burnup, and flux and power distributions, as well as for the reactivity effects which are important in assessing the impact of LEU fuel on reactor shutdown margin. (author)

Core physics analysis in support of the FNR HEU-LEU demonstration experiment

International Nuclear Information System (INIS)

Losey, David C.; Brown, Forrest B.; Martin, William R.; Lee, John C.

1983-01-01

A core neutronics analysis has been undertaken to assess the impact of low-enrichment fuel on the performance and utilization of the FNR As part of this analytic effort a computer code system has been assembled which will be of general use in analyzing research reactors with MTR-type fuel. The code system has been extensively tested and verified in calculations for the present high enrichment core. The analysis presented here compares the high-and-low enrichment fuels in batch and equilibrium core configurations which model the actual FNR operating conditions. The two fuels are compared for cycle length, fuel burnup, and flux and power distributions, as well as for the reactivity effects which are important in assessing the impact of LEU fuel on reactor shutdown margin. (author)

FlpS, the FNR-Like Protein of Streptococcus suis Is an Essential, Oxygen-Sensing Activator of the Arginine Deiminase System

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Jörg Willenborg

2016-07-01

Full Text Available Streptococcus (S. suis is a zoonotic pathogen causing septicemia and meningitis in pigs and humans. During infection S. suis must metabolically adapt to extremely diverse environments of the host. CcpA and the FNR family of bacterial transcriptional regulators are important for metabolic gene regulation in various bacteria. The role of CcpA in S. suis is well defined, but the function of the FNR-like protein of S. suis, FlpS, is yet unknown. Transcriptome analyses of wild-type S. suis and a flpS mutant strain suggested that FlpS is involved in the regulation of the central carbon, arginine degradation and nucleotide metabolism. However, isotopologue profiling revealed no substantial changes in the core carbon and amino acid de novo biosynthesis. FlpS was essential for the induction of the arcABC operon of the arginine degrading pathway under aerobic and anaerobic conditions. The arcABC-inducing activity of FlpS could be associated with the level of free oxygen in the culture medium. FlpS was necessary for arcABC-dependent intracellular bacterial survival but redundant in a mice infection model. Based on these results, we propose that the core function of S. suis FlpS is the oxygen-dependent activation of the arginine deiminase system.

Agent-based modeling of oxygen-responsive transcription factors in Escherichia coli.

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Hao Bai

2014-04-01

Full Text Available In the presence of oxygen (O2 the model bacterium Escherichia coli is able to conserve energy by aerobic respiration. Two major terminal oxidases are involved in this process - Cyo has a relatively low affinity for O2 but is able to pump protons and hence is energetically efficient; Cyd has a high affinity for O2 but does not pump protons. When E. coli encounters environments with different O2 availabilities, the expression of the genes encoding the alternative terminal oxidases, the cydAB and cyoABCDE operons, are regulated by two O2-responsive transcription factors, ArcA (an indirect O2 sensor and FNR (a direct O2 sensor. It has been suggested that O2-consumption by the terminal oxidases located at the cytoplasmic membrane significantly affects the activities of ArcA and FNR in the bacterial nucleoid. In this study, an agent-based modeling approach has been taken to spatially simulate the uptake and consumption of O2 by E. coli and the consequent modulation of ArcA and FNR activities based on experimental data obtained from highly controlled chemostat cultures. The molecules of O2, transcription factors and terminal oxidases are treated as individual agents and their behaviors and interactions are imitated in a simulated 3-D E. coli cell. The model implies that there are two barriers that dampen the response of FNR to O2, i.e. consumption of O2 at the membrane by the terminal oxidases and reaction of O2 with cytoplasmic FNR. Analysis of FNR variants suggested that the monomer-dimer transition is the key step in FNR-mediated repression of gene expression.

Crevicular Fluid and Serum Concentrations of Progranulin and High Sensitivity CRP in Chronic Periodontitis and Type 2 Diabetes

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N. Priyanka

2013-01-01

Full Text Available Introduction. This study was designed to correlate the serum and gingival crevicular fluid (GCF levels of progranulin (PGRN and high sensitivity C-reactive protein (hs CRP in chronic periodontitis and type 2 diabetes mellitus (DM. Design. PGRN and hs CRP levels were estimated in 3 groups: healthy, chronic periodontitis, and type 2 DM with chronic periodontitis. Results. The mean PGRN and hs CRP concentrations in serum and GCF were the highest for group 3 followed by group 2 and the least in group 1. Conclusion. PGRN and hs CRP may be biomarkers of the inflammatory response in type 2 DM and chronic periodontitis.

Crevicular Fluid and Serum Concentrations of Progranulin and High Sensitivity CRP in Chronic Periodontitis and Type 2 Diabetes

Science.gov (United States)

Priyanka, N.; Kumari, Minal; Kalra, Nitish; Arjun, P.; Naik, Savitha B.; Pradeep, A. R.

2013-01-01

Introduction. This study was designed to correlate the serum and gingival crevicular fluid (GCF) levels of progranulin (PGRN) and high sensitivity C-reactive protein (hs CRP) in chronic periodontitis and type 2 diabetes mellitus (DM). Design. PGRN and hs CRP levels were estimated in 3 groups: healthy, chronic periodontitis, and type 2 DM with chronic periodontitis. Results. The mean PGRN and hs CRP concentrations in serum and GCF were the highest for group 3 followed by group 2 and the least in group 1. Conclusion. PGRN and hs CRP may be biomarkers of the inflammatory response in type 2 DM and chronic periodontitis. PMID:24191130

The cyclic AMP receptor protein, CRP, is required for both virulence and expression of the minimal CRP regulon in Yersinia pestis biovar microtus.

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Zhan, Lingjun; Han, Yanping; Yang, Lei; Geng, Jing; Li, Yingli; Gao, He; Guo, Zhaobiao; Fan, Wei; Li, Gang; Zhang, Lianfeng; Qin, Chuan; Zhou, Dongsheng; Yang, Ruifu

2008-11-01

The cyclic AMP receptor protein (CRP) is a bacterial regulator that controls more than 100 promoters, including those involved in catabolite repression. In the present study, a null deletion of the crp gene was constructed for Yersinia pestis bv. microtus strain 201. Microarray expression analysis disclosed that at least 6% of Y. pestis genes were affected by this mutation. Further reverse transcription-PCR and electrophoretic mobility shift assay analyses disclosed a set of 37 genes or putative operons to be the direct targets of CRP, and thus they constitute the minimal CRP regulon in Y. pestis. Subsequent primer extension and DNase I footprinting assays mapped transcriptional start sites, core promoter elements, and CRP binding sites within the DNA regions upstream of pla and pst, revealing positive and direct control of these two laterally acquired plasmid genes by CRP. The crp disruption affected both in vitro and in vivo growth of the mutant and led to a >15,000-fold loss of virulence after subcutaneous infection but a pestis and, particularly, is more important for infection by subcutaneous inoculation. It can further be concluded that the reduced in vivo growth phenotype of the crp mutant should contribute, at least partially, to its attenuation of virulence by both routes of infection. Consistent with a previous study of Y. pestis bv. medievalis, lacZ reporter fusion analysis indicated that the crp deletion resulted in the almost absolute loss of pla promoter activity. The plasminogen activator encoded by pla was previously shown to specifically promote Y. pestis dissemination from peripheral infection routes (subcutaneous infection [flea bite] or inhalation). The above evidence supports the notion that in addition to the reduced in vivo growth phenotype, the defect of pla expression in the crp mutant will greatly contribute to the huge loss of virulence of this mutant strain in subcutaneous infection.

Association of CRP gene polymorphism with CRP levels and Coronary Artery Disease in Type 2 Diabetes in Ahvaz, southwest of Iran

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Ghaffari, Mohammad Ali; Askari Sede, Saeed; Rashtchizadeh, Nadereh; Mohammadzadeh, Ghorban; Majidi, Shahla

2014-01-01

Introduction: We evaluated the association between four polymorphisms in the CRP gene with serum C-reactive protein (CRP) levels, prevalence and severity of coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients. Methods: We performed coronary angiography for 308 T2DM patients and classified them into two groups: T2DM with CAD and T2DM without CAD. All patients were from Ahvaz, Iran. serum levels of CRP, glucose and lipid profile were measured. Genotyping was performed by PCR/RFLP, and the severity of coronary artery disease was determined by Gensini score. Results: The GG genotype of SNP rs279421 was associated with the increased risk of CAD (OR= 2.38; 95% CI: 1.12- 5.8; p= 0.02) and CA, TT, TA genotypes and A allele of SNP rs3091244 and GA genotypes and A allele of SNP rs3093062 were significantly associated with increased CRP levels. None of genotypes or alleles was associated with Gensini score. We found that the haplotype 7 (AGCG) was associated with decreased risk of CAD (OR= 0.11; 95% CI: 0.02, 0.66; p= 0.017) and the Gensini score was correlated with increased levels of CRP, only in CAD group. Conclusion: Although genetic polymorphisms were influenced on serum RP levels, none of the alleles and genotypes raising or falling C-reactive protein levels was consistently associated with an increased prevalence of CAD or protected from that. PMID:25337466

Research promotion of the FNR on biofuels. Energy from algae; Forschungsfoerderung der FNR zu Biokraftstoffen. Energie aus Algen

Energy Technology Data Exchange (ETDEWEB)

Spittel, Maria [Fachagentur Nachwachsende Rohstoffe e.V. (FNR), Guelzow (Germany). Abt. Projektmanagement

2012-07-01

There is an increasing interest in biofuels motivated mainly by climate and environment conservation aspects, but also due to aiming at more independence in fuel supply security. Biofuels had a share of 5,6 % (33.7 TWh) in the total fuel consumption in 2011. The total turnover in the biofuel sector added up to about 3,350 Mill. EUR, showing its economic importance. In this context algae technology is becoming more and more prominent. Algae are seen as alternative resource with increasing importance for the production of biofuels. However, the viability of the involved production and conversion processes are strongly connected to further development and increasing efficiency of algae biotechnology. To date, using algae for energy purposes only is economically not viable. The synergetic combination of industrial and energetic uses of algae will become more important in the future. The Agency for Renewable Resources (FNR) funds innovative R and D and demonstration projects in the framework of the funding program ''Renewable Resources'' initiated by the German Ministry of Food Agriculture and Consumer Protection (BMELV). In this context, FNR supports the optimisation of already commercialised biofuels as well as the further development of future options like fuels from algae biomass. (orig.)

Haplotypes in the CRP Gene Associated with Increased BMI and Levels of CRP in Subjects with Type 2 Diabetes or Obesity from Southwestern Mexico

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América Martínez-Calleja

2012-01-01

Full Text Available Objective. We evaluated the association between four polymorphisms in the CRP gene with circulating levels of C-reactive protein (CRP, type 2 diabetes (T2D, obesity, and risk score of coronary heart disease. Methods. We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology. Results. The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG was associated with increased levels of CRP (β=0.3; 95%CI: 0.1, 0.5; P=0.005 and haplotype 7 (TGGG with higher body mass index (BMI (β=0.2; 95%CI: 0.1, 0.3; P<0.001. The risk score for coronary heart disease was associated with increased levels of CRP, but not with any polymorphism or haplotype. Conclusions. The association between the TT genotype of SNP rs1130864 with obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico.

Haplotypes in the CRP gene associated with increased BMI and levels of CRP in subjects with type 2 diabetes or obesity from Southwestern Mexico.

Science.gov (United States)

Martínez-Calleja, América; Quiróz-Vargas, Irma; Parra-Rojas, Isela; Muñoz-Valle, José Francisco; Leyva-Vázquez, Marco A; Fernández-Tilapa, Gloria; Vences-Velázquez, Amalia; Cruz, Miguel; Salazar-Martínez, Eduardo; Flores-Alfaro, Eugenia

2012-01-01

We evaluated the association between four polymorphisms in the CRP gene with circulating levels of C-reactive protein (CRP), type 2 diabetes (T2D), obesity, and risk score of coronary heart disease. We studied 402 individuals and classified them into four groups: healthy, obese, T2D obese, and T2D without obesity, from Guerrero, Southwestern Mexico. Blood levels of CRP, glucose, cholesterol, triglycerides, and leukocytes were measured. Genotyping was performed by PCR/RFLP, and the risk score for coronary heart disease was determined by the Framingham's methodology. The TT genotype of SNP rs1130864 was associated with increased body mass index and T2D patients with obesity. We found that the haplotype 2 (TGAG) was associated with increased levels of CRP (β = 0.3; 95%CI: 0.1, 0.5; P = 0.005) and haplotype 7 (TGGG) with higher body mass index (BMI) (β = 0.2; 95%CI: 0.1, 0.3; P obesity and the haplotype 7 with BMI may explain how obesity and genetic predisposition increase the risk of diseases such as T2D in the population of Southwestern Mexico.

Combined effect of loss of the caa3 oxidase and Crp regulation drives Shewanella to thrive in redox-stratified environments.

Science.gov (United States)

Zhou, Guangqi; Yin, Jianhua; Chen, Haijiang; Hua, Yijie; Sun, Linlin; Gao, Haichun

2013-09-01

Shewanella species are a group of facultative Gram-negative microorganisms with remarkable respiration abilities that allow the use of a diverse array of terminal electron acceptors (EA). Like most bacteria, S. oneidensis possesses multiple terminal oxidases, including two heme-copper oxidases (caa3- and cbb3-type) and a bd-type quinol oxidase. As aerobic respiration is energetically favored, mechanisms underlying the fact that these microorganisms thrive in redox-stratified environments remain vastly unexplored. In this work, we discovered that the cbb3-type oxidase is the predominant system for respiration of oxygen (O2), especially when O2 is abundant. Under microaerobic conditions, the bd-type quinol oxidase has a significant role in addition to the cbb3-type oxidase. In contrast, multiple lines of evidence suggest that under test conditions the caa3-type oxidase, an analog to the mitochondrial enzyme, has no physiological significance, likely because of its extremely low expression. In addition, expression of both cbb3- and bd-type oxidases is under direct control of Crp (cAMP receptor protein) but not the well-established redox regulator Fnr (fumarate nitrate regulator) of canonical systems typified in Escherichia coli. These data, collectively, suggest that adaptation of S. oneidensis to redox-stratified environments is likely due to functional loss of the caa3-type oxidase and switch of the regulatory system for respiration.

Elevated Expression of GlpT and UhpT via FNR Activation Contributes to Increased Fosfomycin Susceptibility in Escherichia coli under Anaerobic Conditions

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Kurabayashi, Kumiko; Tanimoto, Koichi; Fueki, Shinobu; Tomita, Haruyoshi

2015-01-01

Because a shortage of new antimicrobial agents is a critical issue at present, and with the spread of multidrug-resistant (MDR) pathogens, the use of fosfomycin to treat infections is being revisited as a “last-resort option.” This drug offers a particular benefit in that it is more effective against bacteria growing under oxygen-limited conditions, unlike other commonly used antimicrobials, such as fluoroquinolones and aminoglycosides. In this study, we showed that Escherichia coli strains, including enterohemorrhagic E. coli (EHEC), were more susceptible to fosfomycin when grown anaerobically than when grown aerobically, and we investigated how the activity of this drug was enhanced during anaerobic growth of E. coli. Our quantitative PCR analysis and a transport assay showed that E. coli cells grown under anaerobic conditions had higher levels of expression of glpT and uhpT, encoding proteins that transport fosfomycin into cells with their native substrates, i.e., glycerol-3-phosphate and glucose-6-phosphate, and led to increased intracellular accumulation of the drug. Elevation of expression of these genes during anaerobic growth requires FNR, a global transcriptional regulator that is activated under anaerobic conditions. Purified FNR bound to DNA fragments from regions upstream of glpT and uhpT, suggesting that it is an activator of expression of glpT and uhpT during anaerobic growth. We concluded that the increased antibacterial activity of fosfomycin toward E. coli under anaerobic conditions can be attributed to elevated expression of GlpT and UhpT following activation of FNR, leading to increased uptake of the drug. PMID:26248376

Correlation of hs-CRP with environmental risk factors of nephropathy in type 2 diabetes

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Jay Prakash Sah

2015-06-01

Full Text Available The objective of the present study was to investigate the association of hs-CRP levels with environmental risk factors of diabetic nephropathy like smoking, drinking alcohol, diet, age of diabetic patient, duration of diabetes, medication of diabetes, and blood pressure medication. A hospital-based quantitative study was conducted at the Department of Clinical Biochemistry of Manipal Teaching Hospital (MTH Pokhara, Nepal, with 89 patients suffering from type 2 diabetes. Blood samples (n=89 from the patients were collected and the serums were separated. On the other hand, data on environmental risk factors of nephropathy were collected by using standard questionnaire. In this study, serum hs-CRP level was not found to be correlated with smoking (p=0.111, alcohol consumption (p=0.722, diet (p=0.496, duration of diabetes (p=0.519, age of diabetic patient (p=0.369, medication of diabetes (p=0.734, and blood pressure medication (p=0.625. Hence, our study concludes that serum hs-CRP value in type 2 diabetic patients is insignificantly correlated with the risk factors especially smoking, drinking alcohol, diet, duration of diabetes, age of diabetic patient, medication of diabetes, and medication of blood pressure.

Sequence and Genetic Characterization of etrA, an fnr Analog that Regulates Anaerobic Respiration in Shewanella putrefaciens MR-1

Science.gov (United States)

Saffarini, Daad A.; Nelson, Kenneth H.

1993-01-01

An electron transport regulatory gene, etrA, has been isolated and characterized from the obligate respiratory bacterium Shewanella putrefaciens MR-l. The deduced amino acid sequence of etrA (EtrA) shows a high degree of identity to both the Fnr of Escherichia coli (73.6%) and the analogous protein (ANR) of Pseudomonas aeruginosa (50.8%). The four active cysteine residues of Fnr are conserved in EtrA, and the amino acid sequence of the DNA-binding domains of the two proteins are identical. Further, S.putrefaciens etrA is able to complement an fnr mutant of E.coli. In contrast to fnr, there is no recognizable Fnr box upstream of the etrA sequence. Gene replacement etr.A mutants of MR-1 were deficient in growth on nitrite, thiosulfate, sulfite, trimethylamine-N-oxide, dimethyl sulfoxide, Fe(III), and fumarate, suggesting that EtrA is involved in the regulation of the corresponding reductase genes. However, the mutants were all positive for reduction of and growth on nitrate and Mn(IV), indicating that EtrA is not involved in the regulation of these two systems. Southern blots of S.putrefaciens DNA with use of etrA as a probe revealed the expected etrA bands and a second set of hybridization signals whose genetic and functional properties remain to be determined.

Cytoskeleton-interacting LIM-domain protein CRP1 suppresses cell proliferation and protects from stress-induced cell death

International Nuclear Information System (INIS)

Latonen, Leena; Jaervinen, Paeivi M.; Laiho, Marikki

2008-01-01

Members of the cysteine-rich protein (CRP) family are actin cytoskeleton-interacting LIM-domain proteins known to act in muscle cell differentiation. We have earlier found that CRP1, a founding member of this family, is transcriptionally induced by UV radiation in human diploid fibroblasts [M. Gentile, L. Latonen, M. Laiho, Cell cycle arrest and apoptosis provoked by UV radiation-induced DNA damage are transcriptionally highly divergent responses, Nucleic Acids Res. 31 (2003) 4779-4790]. Here we show that CRP1 is induced by growth-inhibitory signals, such as increased cellular density, and cytotoxic stress induced by UV radiation or staurosporine. We found that high levels of CRP1 correlate with differentiation-associated morphology towards the myofibroblast lineage and that expression of ectopic CRP1 suppresses cell proliferation. Following UV- and staurosporine-induced stresses, expression of CRP1 provides a survival advantage evidenced by decreased cellular death and increased cellular metabolic activity and attachment. Our studies identify that CRP1 is a novel stress response factor, and provide evidence for its growth-inhibitory and cytoprotective functions

CRP-dependent positive autoregulation and proteolytic degradation regulate competence activator Sxy of Escherichia coli

DEFF Research Database (Denmark)

Jaskólska, Milena; Gerdes, Kenn

2015-01-01

is positively autoregulated at the level of transcription by a mechanism that requires cAMP receptor protein (CRP), cyclic AMP (cAMP) and a CRP-S site in the sxy promoter. Similarly, we found no evidence that Sxy expression in E. coli was regulated at the translational level. However, our analysis revealed...

Operating experience, measurements, and analysis of the LEU whole core demonstration at the FNR

International Nuclear Information System (INIS)

Weha, D.K.; Drumm, C.R.; King, J.S.; Martin, W.R.; Lee, J.C.

1984-01-01

The 2-MW Ford Nuclear Reactor at the University of Michigan is serving as the demonstration reactor for the MTR-type low enrichment (LEU) fuel for the Reduced Enrichment for Research and Test Reactor program. Operational experience gained through six months of LEU core operation and seven months of mixed HEU-LEU core operation is presented. Subcadmium flux measurements performed with rhodium self-powered neutron detectors and iron wire activations are compared with calculations. Measured reactivity parameters are compared for HEU and LEU cores. Finally, the benchmark calculations for several HEU, LEU, and mixed HEU-LEU FNR cores and the International Atomic Energy Agency (IAEA) benchmark problem are presented. (author)

Binding behavior of CRP and anti-CRP antibody analyzed with SPR and AFM measurement

International Nuclear Information System (INIS)

Lee, Soo-Keun; Kim, Hyun-Chul; Cho, Sang-Joon; Jeong, Sang Won; Jeon, Won Bae

2008-01-01

Atomic force microscope (AFM) was exploited to take picture of the molecular topology of C-reactive protein (CRP) in phosphate-buffered saline (PBS) solution. An explicit molecular image of CRP demonstrated a pentagonal structure composed of five subunits. Dimensions of the doughnut-shaped CRP molecule measured by AFM were about 25 nm in outside diameter and 10 nm in central pore diameter, and the height of CRP molecule was about 4 nm which was comparable to the value determined by X-ray crystallography. Bis(N-succinimido)-11,11'-dithiobis (undecyl succinate) (DSNHS) was synthesized for use as a linker for immobilizing anti-CRP antibody (anti-CRP) onto the gold surface of a surface plasmon resonance (SPR) sensor chip. DSNHS formed self-assembled monolayer (SAM) on the gold surface. By use of an AFM tip, a pattern of ditch was engraved within the SAM of DSNHS, and anti-CRP was immobilized on the engraved SAM through replacement of N-hydroxysuccinimide group on the outside surface of DSNHS by the amine group of anti-CRP. Formation of CRP/anti-CRP complex on the gold surface of SPR sensor chip was clearly demonstrated by measuring SPR angle shift. A consecutive series of SAM, SAM/anti-CRP, and SAM/anti-CRP/CRP complexes was generated on a SPR sensor chip, and the changes in depth of the ditch were monitored by taking AFM images of the complexes. Comparative analysis of the depth differences indicates that binding of CRP to anti-CRP occurs in a planar mode

Serum C-reactive protein (CRP) as a simple and independent prognostic factor in extranodal natural killer/T-cell lymphoma, nasal type.

Science.gov (United States)

Li, Ya-Jun; Li, Zhi-Ming; Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

2013-01-01

C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (PKPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.

Computational prediction of cAMP receptor protein (CRP binding sites in cyanobacterial genomes

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Su Zhengchang

2009-01-01

Full Text Available Abstract Background Cyclic AMP receptor protein (CRP, also known as catabolite gene activator protein (CAP, is an important transcriptional regulator widely distributed in many bacteria. The biological processes under the regulation of CRP are highly diverse among different groups of bacterial species. Elucidation of CRP regulons in cyanobacteria will further our understanding of the physiology and ecology of this important group of microorganisms. Previously, CRP has been experimentally studied in only two cyanobacterial strains: Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120; therefore, a systematic genome-scale study of the potential CRP target genes and binding sites in cyanobacterial genomes is urgently needed. Results We have predicted and analyzed the CRP binding sites and regulons in 12 sequenced cyanobacterial genomes using a highly effective cis-regulatory binding site scanning algorithm. Our results show that cyanobacterial CRP binding sites are very similar to those in E. coli; however, the regulons are very different from that of E. coli. Furthermore, CRP regulons in different cyanobacterial species/ecotypes are also highly diversified, ranging from photosynthesis, carbon fixation and nitrogen assimilation, to chemotaxis and signal transduction. In addition, our prediction indicates that crp genes in modern cyanobacteria are likely inherited from a common ancestral gene in their last common ancestor, and have adapted various cellular functions in different environments, while some cyanobacteria lost their crp genes as well as CRP binding sites during the course of evolution. Conclusion The CRP regulons in cyanobacteria are highly diversified, probably as a result of divergent evolution to adapt to various ecological niches. Cyanobacterial CRPs may function as lineage-specific regulators participating in various cellular processes, and are important in some lineages. However, they are dispensable in some other lineages. The

Enhancing E. coli tolerance towards oxidative stress via engineering its global regulator cAMP receptor protein (CRP.

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Souvik Basak

Full Text Available Oxidative damage to microbial hosts often occurs under stressful conditions during bioprocessing. Classical strain engineering approaches are usually both time-consuming and labor intensive. Here, we aim to improve E. coli performance under oxidative stress via engineering its global regulator cAMP receptor protein (CRP, which can directly or indirectly regulate redox-sensing regulators SoxR and OxyR, and other ~400 genes in E. coli. Error-prone PCR technique was employed to introduce modifications to CRP, and three mutants (OM1~OM3 were identified with improved tolerance via H(2O(2 enrichment selection. The best mutant OM3 could grow in 12 mM H(2O(2 with the growth rate of 0.6 h(-1, whereas the growth of wild type was completely inhibited at this H(2O(2 concentration. OM3 also elicited enhanced thermotolerance at 48°C as well as resistance against cumene hydroperoxide. The investigation about intracellular reactive oxygen species (ROS, which determines cell viability, indicated that the accumulation of ROS in OM3 was always lower than in WT with or without H(2O(2 treatment. Genome-wide DNA microarray analysis has shown not only CRP-regulated genes have demonstrated great transcriptional level changes (up to 8.9-fold, but also RpoS- and OxyR-regulated genes (up to 7.7-fold. qRT-PCR data and enzyme activity assay suggested that catalase (katE could be a major antioxidant enzyme in OM3 instead of alkyl hydroperoxide reductase or superoxide dismutase. To our knowledge, this is the first work on improving E. coli oxidative stress resistance by reframing its transcription machinery through its native global regulator. The positive outcome of this approach may suggest that engineering CRP can be successfully implemented as an efficient strain engineering alternative for E. coli.

Plasticity of regulation of mannitol phosphotransferase system operon by CRP-cAMP complex in Vibrio cholerae.

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Zhou, Yan Yan; Zhang, Hong Zhi; Liang, Wei Li; Zhang, Li Juan; Zhu, Jun; Kan, Biao

2013-10-01

The complex of the cyclic AMP receptor protein (CRP) and cAMP is an important transcriptional regulator of numerous genes in prokaryotes. The transport of mannitol through the phosphotransferase systems (PTS) is regulated by the CRP-cAMP complex. The aim of the study is to investigate how the CRP-cAMP complex acting on the mannitol PTS operon mtl of the Vibrio cholerae El Tor biotype. The crp mutant strain was generated by homologous recombination to assess the need of CRP to activate the mannitol PTS operon of V. cholerae El Tor. Electrophoretic mobility shift assays (EMSA) and the reporter plasmid pBBRlux were used to confirm the role that the CRP-cAMP complex playing on the mannitol PTS operon mtl. In this study, we confirmed that CRP is strictly needed for the activation of the mtl operon. We further experimentally identified five CRP binding sites within the promoter region upstream of the mannitol PTS operon mtl of the Vibrio cholerae El Tor biotype and found that these sites display different affinities for CRP and provide different contributions to the activation of the operon. The five binding sites collectively confer the strong activation of mannitol transfer by CRP in V. cholerae, indicating an elaborate and subtle CRP activation mechanism. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

ExtraTrain: a database of Extragenic regions and Transcriptional information in prokaryotic organisms

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Pareja, Eduardo; Pareja-Tobes, Pablo; Manrique, Marina; Pareja-Tobes, Eduardo; Bonal, Javier; Tobes, Raquel

2006-01-01

Background Transcriptional regulation processes are the principal mechanisms of adaptation in prokaryotes. In these processes, the regulatory proteins and the regulatory DNA signals located in extragenic regions are the key elements involved. As all extragenic spaces are putative regulatory regions, ExtraTrain covers all extragenic regions of available genomes and regulatory proteins from bacteria and archaea included in the UniProt database. Description ExtraTrain provides integrated and easily manageable information for 679816 extragenic regions and for the genes delimiting each of them. In addition ExtraTrain supplies a tool to explore extragenic regions, named Palinsight, oriented to detect and search palindromic patterns. This interactive visual tool is totally integrated in the database, allowing the search for regulatory signals in user defined sets of extragenic regions. The 26046 regulatory proteins included in ExtraTrain belong to the families AraC/XylS, ArsR, AsnC, Cold shock domain, CRP-FNR, DeoR, GntR, IclR, LacI, LuxR, LysR, MarR, MerR, NtrC/Fis, OmpR and TetR. The database follows the InterPro criteria to define these families. The information about regulators includes manually curated sets of references specifically associated to regulator entries. In order to achieve a sustainable and maintainable knowledge database ExtraTrain is a platform open to the contribution of knowledge by the scientific community providing a system for the incorporation of textual knowledge. Conclusion ExtraTrain is a new database for exploring Extragenic regions and Transcriptional information in bacteria and archaea. ExtraTrain database is available at . PMID:16539733

High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes.

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McDonald, Tim J; Shields, Beverley M; Lawry, Jane; Owen, Katharine R; Gloyn, Anna L; Ellard, Sian; Hattersley, Andrew T

2011-08-01

Maturity-onset diabetes of the young (MODY) as a result of mutations in hepatocyte nuclear factor 1-α (HNF1A) is often misdiagnosed as type 1 diabetes or type 2 diabetes. Recent work has shown that high-sensitivity C-reactive protein (hs-CRP) levels are lower in HNF1A-MODY than type 1 diabetes, type 2 diabetes, or glucokinase (GCK)-MODY. We aim to replicate these findings in larger numbers and other MODY subtypes. hs-CRP levels were assessed in 750 patients (220 HNF1A, 245 GCK, 54 HNF4-α [HNF4A], 21 HNF1-β (HNF1B), 53 type 1 diabetes, and 157 type 2 diabetes). hs-CRP was lower in HNF1A-MODY (median [IQR] 0.3 [0.1-0.6] mg/L) than type 2 diabetes (1.40 [0.60-3.45] mg/L; P MODY (1.45 [0.46-2.88] mg/L; P MODY (0.60 [0.30-1.80] mg/L; P MODY (0.60 [0.10-2.8] mg/L; P = 0.07). hs-CRP discriminated HNF1A-MODY from type 2 diabetes with hs-CRP MODY than other forms of diabetes and may be used as a biomarker to select patients for diagnostic HNF1A genetic testing.

Cyclic AMP Receptor Protein Acts as a Transcription Regulator in Response to Stresses in Deinococcus radiodurans.

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Su Yang

Full Text Available The cyclic AMP receptor protein family of transcription factors regulates various metabolic pathways in bacteria, and also play roles in response to environmental changes. Here, we identify four homologs of the CRP family in Deinococcus radiodurans, one of which tolerates extremely high levels of oxidative stress and DNA-damaging reagents. Transcriptional levels of CRP were increased under hydrogen peroxide (H2O2 treatment during the stationary growth phase, indicating that CRPs function in response to oxidative stress. By constructing all CRP single knockout mutants, we found that the dr0997 mutant showed the lowest tolerance toward H2O2, ultraviolet radiation, ionizing radiation, and mitomycin C, while the phenotypes of the dr2362, dr0834, and dr1646 mutants showed slight or no significant differences from those of the wild-type strain. Taking advantage of the conservation of the CRP-binding site in many bacteria, we found that transcription of 18 genes, including genes encoding chromosome-partitioning protein (dr0998, Lon proteases (dr0349 and dr1974, NADH-quinone oxidoreductase (dr1506, thiosulfate sulfurtransferase (dr2531, the DNA repair protein UvsE (dr1819, PprA (dra0346, and RecN (dr1447, are directly regulated by DR0997. Quantitative real-time polymerase chain reaction (qRT-PCR analyses showed that certain genes involved in anti-oxidative responses, DNA repair, and various cellular pathways are transcriptionally attenuated in the dr0997 mutant. Interestingly, DR0997 also regulate the transcriptional levels of all CRP genes in this bacterium. These data suggest that DR0997 contributes to the extreme stress resistance of D. radiodurans via its regulatory role in multiple cellular pathways, such as anti-oxidation and DNA repair pathways.

Increased LDL cholesterol and CRP in infants of mothers with type 1 diabetes

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Lindegaard, Marie Louise Skakkebæk; Svarrer, Eva Martha Madsen; Damm, Peter

2008-01-01

Proatherogenic stimuli during foetal life may predispose to development of atherosclerosis in adulthood. Elevated plasma low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) expression is associated with increased risk of atherosclerosis.......Proatherogenic stimuli during foetal life may predispose to development of atherosclerosis in adulthood. Elevated plasma low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) expression is associated with increased risk of atherosclerosis....

The correlation between changes of C-reactive protein (CRP level and size of infarct in stroke

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Shahram Aboutalebi

2006-09-01

Full Text Available Background: The presence of C-reactive protein (CRP during different stages of stroke had been shown in several studies. There is still no definite document about the correlation of CRP level and size of infarct in stroke. We studied the correlation of the acute level of CRP with size of infarct in stroke. Methods: A total of 90 consecutive patients with acute stroke admitted in Fatemeh Zahra University Hospital in Bushehr city were studied. Levels of CRP were measured at admission time and 48 hours later. Sizes of infarct and types of stroke were determined with Computerized Tomography scanning. The excluded patients were those with infection, stroke in brain stem, a delay more than 24 hours after attack of stroke and Transient Ischemic Attacks. CRP level was measured quantitatively using ELISA method. Results: No correlation between the first CRP levels and variables of age, size of infarct and type of stroke was detected. Size of infarct was correlated with the second CRP (r=0.41, P<0.001 and the difference in CRP levels (r=0.45, P<0.001. The CRP difference was significant in ischemic, hemorrhagic and territory infarcts (P<0.01. But there was no difference between the first and the second CRP in lacunar infarcts. Conclusion: We found no correlation between the CRP levels of the 24 first hours after acute stroke with size of infarct in stroke. But the increase of CRP levels which were measured in 48 hours after the stroke had correlation with size of infarct irrespective of types of stroke. More studies could reveal the cause and effect of CRP in size of infarct in stroke.

Inflammation, insulin resistance, and diabetes--Mendelian randomization using CRP haplotypes points upstream.

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Eric J Brunner

2008-08-01

Full Text Available Raised C-reactive protein (CRP is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables.We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study. Homeostasis model assessment-insulin resistance (HOMA-IR and hemoglobin A1c (HbA1c were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52-0.92. The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007-0.11. Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25-0.88. Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls using three SNPs in tight linkage disequilibrium with our

Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP-C1q interaction

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Sjoewall, Christopher; Wetteroe, Jonas; Bengtsson, Torbjoern; Askendal, Agneta; Almroth, Gunnel; Skogh, Thomas; Tengvall, Pentti

2007-01-01

C-reactive protein (CRP) interacts with phosphorylcholine (PC), Fcγ receptors, complement factor C1q and cell nuclear constituents, yet its biological roles are insufficiently understood. The aim was to characterize CRP-induced complement activation by ellipsometry. PC conjugated with keyhole limpet hemocyanin (PC-KLH) was immobilized to cross-linked fibrinogen. A low-CRP serum with different amounts of added CRP was exposed to the PC-surfaces. The total serum protein deposition was quantified and deposition of IgG, C1q, C3c, C4, factor H, and CRP detected with polyclonal antibodies. The binding of serum CRP to PC-KLH dose-dependently triggered activation of the classical pathway. Unexpectedly, the activation was efficiently down-regulated at CRP levels >150 mg/L. Using radial immunodiffusion, CRP-C1q interaction was observed in serum samples with high CRP concentrations. We propose that the underlying mechanism depends on fluid-phase interaction between C1q and CRP. This might constitute another level of complement regulation, which has implications for systemic lupus erythematosus where CRP is often low despite flare-ups

Electrochemical investigations of the interaction of C-reactive protein (CRP) with a CRP antibody chemically immobilized on a gold surface

International Nuclear Information System (INIS)

Hennessey, Hooman; Afara, Nadia; Omanovic, Sasha; Padjen, Ante L.

2009-01-01

A possibility of using a range of dc and ac electrochemical techniques to probe associative interactions of C-reactive protein (CRP) with CRP antibody (aCRP) immobilized on a gold electrode surface was investigated. It was demonstrated that the investigated electrochemical techniques can be used efficiently to probe these interactions over a wide CRP concentration range, from 1.15 x 10 -5 to 1.15 mg L -1 . The measured sensitivity of the techniques is in the following decreasing order: differential pulse voltammetry, charge-transfer resistance obtained from electrochemical impedance spectroscopy (EIS), cyclic voltammetry, chronoamperometry, and double-layer capacitance deduced from EIS measurements which gave the poorest sensitivity. Measurements of kinetic parameters demonstrated that the associative interactions of CRP with the immobilized aCRP reached quasi-equilibrium after 20-30 min. The kinetics of these interactions was modeled successfully using a two-step kinetic model. In this model, the first step represents reversible CRP-aCRP associative-dissociative interactions, while the second step represents the irreversible transformation of the bound CRP into a thermodynamically stable configuration. It was demonstrated that the thermodynamically stable configuration of CRP starts prevailing after 7 min of interaction of CRP with the immobilized aCRP.

Rapid and Low-Cost CRP Measurement by Integrating a Paper-Based Microfluidic Immunoassay with Smartphone (CRP-Chip)

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Dong, Meili; Wu, Jiandong; Ma, Zimin; Peretz-Soroka, Hagit; Zhang, Michael; Komenda, Paul; Tangri, Navdeep; Liu, Yong; Rigatto, Claudio; Lin, Francis

2017-01-01

Traditional diagnostic tests for chronic diseases are expensive and require a specialized laboratory, therefore limiting their use for point-of-care (PoC) testing. To address this gap, we developed a method for rapid and low-cost C-reactive protein (CRP) detection from blood by integrating a paper-based microfluidic immunoassay with a smartphone (CRP-Chip). We chose CRP for this initial development because it is a strong biomarker of prognosis in chronic heart and kidney disease. The microfluidic immunoassay is realized by lateral flow and gold nanoparticle-based colorimetric detection of the target protein. The test image signal is acquired and analyzed using a commercial smartphone with an attached microlens and a 3D-printed chip–phone interface. The CRP-Chip was validated for detecting CRP in blood samples from chronic kidney disease patients and healthy subjects. The linear detection range of the CRP-Chip is up to 2 μg/mL and the detection limit is 54 ng/mL. The CRP-Chip test result yields high reproducibility and is consistent with the standard ELISA kit. A single CRP-Chip can perform the test in triplicate on a single chip within 15 min for less than 50 US cents of material cost. This CRP-Chip with attractive features of low-cost, fast test speed, and integrated easy operation with smartphones has the potential to enable future clinical PoC chronic disease diagnosis and risk stratification by parallel measurements of a panel of protein biomarkers. PMID:28346363

Tandem DNA-bound cAMP-CRP complexes are required for transcriptional repression of the deoP2 promoter by the CytR repressor in Escherichia coli

DEFF Research Database (Denmark)

Søgaard-Andersen, Lotte; Møllegaard, N E; Douthwaite, S R

1990-01-01

region, and is sufficient for activation; the second site, CRP-2, centred around -93, is indispensable for repression. Here we demonstrate, by means of in vivo titration, that CytR interaction with deoP2 depends not only on CRP-2, but also on CRP-1 and the length and possibly the sequence separating...... these two sites. Also, point mutations in either CRP site reduce or abolish CytR titration; however, no co-operativity is observed in the interaction of CytR with the two CRP binding sites. Furthermore, the reduction in CytR titration parallels the reduction in binding of cAMP-CRP to the mutated CRP sites...

A Serratia marcescens PigP homolog controls prodigiosin biosynthesis, swarming motility and hemolysis and is regulated by cAMP-CRP and HexS.

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Robert M Q Shanks

Full Text Available Swarming motility and hemolysis are virulence-associated determinants for a wide array of pathogenic bacteria. The broad host-range opportunistic pathogen Serratia marcescens produces serratamolide, a small cyclic amino-lipid, that promotes swarming motility and hemolysis. Serratamolide is negatively regulated by the transcription factors HexS and CRP. Positive regulators of serratamolide production are unknown. Similar to serratamolide, the antibiotic pigment, prodigiosin, is regulated by temperature, growth phase, HexS, and CRP. Because of this co-regulation, we tested the hypothesis that a homolog of the PigP transcription factor of the atypical Serratia species ATCC 39006, which positively regulates prodigiosin biosynthesis, is also a positive regulator of serratamolide production in S. marcescens. Mutation of pigP in clinical, environmental, and laboratory strains of S. marcescens conferred pleiotropic phenotypes including the loss of swarming motility, hemolysis, and severely reduced prodigiosin and serratamolide synthesis. Transcriptional analysis and electrophoretic mobility shift assays place PigP in a regulatory pathway with upstream regulators CRP and HexS. The data from this study identifies a positive regulator of serratamolide production, describes novel roles for the PigP transcription factor, shows for the first time that PigP directly regulates the pigment biosynthetic operon, and identifies upstream regulators of pigP. This study suggests that PigP is important for the ability of S. marcescens to compete in the environment.

The enhanced UV-sensitivity of Escherichia coli uvr A crp strain

International Nuclear Information System (INIS)

Skavronskaya, A.G.; Aleshkin, G.I.

1979-01-01

Mutations in genes cya and crp do not affect the UV cell sensitivity of Escherichia coli of wild type in relation to repairs of UV-injuries and UV induced mutations yield. Mutations in gene crp (protein defect of catabolitic activator - cap) result in UV sensitivity decrease of E. coli uvrA strain, imperfect as to the first stage of excision repairs not decreasing the quantity of revertants, induced by the UV-light

Allexiviruses may have acquired inserted sequences between the CP and CRP genes to change the translation reinitiation strategy of CRP.

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Yoshida, Naoto; Shimura, Hanako; Masuta, Chikara

2018-06-01

Allexiviruses are economically important garlic viruses that are involved in garlic mosaic diseases. In this study, we characterized the allexivirus cysteine-rich protein (CRP) gene located just downstream of the coat protein (CP) gene in the viral genome. We determined the nucleotide sequences of the CP and CRP genes from numerous allexivirus isolates and performed a phylogenetic analysis. According to the resulting phylogenetic tree, we found that allexiviruses were clearly divided into two major groups (group I and group II) based on the sequences of the CP and CRP genes. In addition, the allexiviruses in group II had distinct sequences just before the CRP gene, while group I isolates did not. The inserted sequence between the CP and CRP genes was partially complementary to garlic 18S rRNA. Using a potato virus X vector, we showed that the CRPs affected viral accumulation and symptom induction in Nicotiana benthamiana, suggesting that the allexivirus CRP is a pathogenicity determinant. We assume that the inserted sequences before the CRP gene may have been generated during viral evolution to alter the termination-reinitiation mechanism for coupled translation of CP and CRP.

Acrolein stimulates the synthesis of IL-6 and C-reactive protein (CRP) in thrombosis model mice and cultured cells.

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Saiki, Ryotaro; Hayashi, Daisuke; Ikuo, Yukiko; Nishimura, Kazuhiro; Ishii, Itsuko; Kobayashi, Kaoru; Chiba, Kan; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

2013-12-01

Measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction with high sensitivity and specificity. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP in thrombosis model mice and cultured cells. In mice with photochemically induced thrombosis, acrolein produced at the locus of infarction increased the level of IL-6 and then CRP in plasma. This was confirmed in cell culture systems - acrolein stimulated the production of IL-6 in mouse neuroblastoma Neuro-2a cells, mouse macrophage-like J774.1 cells, and human umbilical vein endothelial cells (HUVEC), and IL-6 in turn stimulated the production of CRP in human hepatocarcinoma cells. The level of IL-6 mRNA was increased by acrolein through an increase in phosphorylation of the transcription factors, c-Jun, and NF-κB p65. Furthermore, CRP stimulated IL-6 production in mouse macrophage-like J774.1 cells and HUVEC. IL-6 functioned as a protective factor against acrolein toxicity in Neuro-2a cells and HUVEC. These results show that acrolein stimulates the synthesis of IL-6 and CRP, which function as protecting factors against acrolein toxicity, and that the combined measurement of PC-Acro, IL-6, and CRP is effective for identification of silent brain infarction. The combined measurements of protein-conjugated acrolein (PC-Acro), IL-6, and C-reactive protein (CRP) in plasma were useful for identifying silent brain infarction. The aim of this study was to determine whether acrolein causes increased production of IL-6 and CRP, and indeed acrolein increased IL-6 synthesis and IL-6 in turn increased CRP synthesis. Furthermore, IL-6 decreased acrolein toxicity in several cell lines. © 2013 International Society for Neurochemistry.

[Impact of metabolic syndrome on CRP levels].

Science.gov (United States)

Rodilla, E; Costa, J A; Mares, S; Miralles, A; González, C; Sánchez, C; Pascual, J M

2006-09-01

C-reactive protein (CRP) is considered a marker of subclinical atherosclerosis. The aim of the study was to assess whether the metabolic syndrome (MS) and parameters involved in its diagnosis might influence serum CRP values. Cross-sectional study in outpatients of a HTA and Vascular Risk clinic. MS was diagnosed according to National Cholesterol Educational Program ATP-III guidelines, and hs-CRP was analyzed by nephelometry. A total of 1,969 patients (47% male) were evaluated and distributed into four groups: 1) 1,220 non-diabetics without MS; 2) 384 non-diabetics with MS; 3) 153 diabetics without MS, and 4) 212 diabetics with MS. Patients with MS had higher CRP in both non-diabetic 3.0 (1.7-4.4) mg/l vs. 1.7 (0.9-3.4) mg/l; p=0.001 (MW), and diabetic patients: 2.8 (1.5-4.6) mg/l vs. 2.2 (0.9-4.3) mg/l; p=0.01 (MW). Diabetic patients without MS had CRP values not different to non-diabetic without MS. CRP values increased in relation to the number of parameters included in the MS from 1.7 (2.2) mg/l, in patients without any parameters, to 4.2 (2.8) mg/l in patients who fulfilled five parameters (p=0.001) (KW). In multiple regression analysis abdominal obesity (p=0.001), TG (p=0.001) and glucose (p=0.02) were associated with CRP levels after correcting for other factors. Abdominal obesity (OR: 1.9; 95% CI: 1.5-2.4; p=0.001) and TG (OR: 1.4; 95% CI: 1.1 -1.7; p=0.003), but not glucose were independent factors related to the presence of high levels of CRP (>3 mg/l) in a logistic regression analysis. Diabetic and non-diabetic patients with MS have high CRP levels. Of the five components of MS, the most closely related to CRP is abdominal obesity.

Dissimilatory Metabolism of Nitrogen Oxides in Bacteria:Comparative Reconstruction of Transcriptional Networks

Energy Technology Data Exchange (ETDEWEB)

Rodionov, Dmitry A.; Dubchak, Inna L.; Arkin, Adam P.; Alm, EricJ.; Gelfand, Mikhail S.

2005-09-01

Bacterial response to nitric oxide (NO) is of major importance since NO is an obligatory intermediate of the nitrogen cycle. Transcriptional regulation of the dissimilatory nitric oxides metabolism in bacteria is diverse and involves FNR-like transcription factors HcpR, DNR and NnrR, two-component systems NarXL and NarQP, NO-responsive activator NorR, and nitrite sensitive repressor NsrR. Using comparative genomics approaches we predict DNA-binding signals for these transcriptional factors and describe corresponding regulons in available bacterial genomes. Within the FNR family of regulators, we observed a correlation of two specificity-determining amino acids and contacting bases in corresponding DNA signal. Highly conserved regulon HcpR for the hybrid cluster protein and some other redox enzymes is present in diverse anaerobic bacteria including Clostridia, Thermotogales and delta-proteobacteria. NnrR and DNR control denitrification in alpha- and beta-proteobacteria, respectively. Sigma-54-dependent NorR regulon found in some gamma- and beta-proteobacteria contains various enzymes involved in the NO detoxification. Repressor NsrR, which was previously known to control only nitrite reductase operon in Nitrosomonas spp., appears to be the master regulator of the nitric oxides metabolism not only in most gamma- and beta-proteobacteria (including well-studied species like Escherichia coli), but also in Gram-positive Bacillus and Streptomyces species. Positional analysis and comparison of regulatory regions of NO detoxification genes allows us to propose the candidate NsrR-binding signal. The most conserved member of the predicted NsrR regulon is the NO-detoxifying flavohemoglobin Hmp. In enterobacteria, the regulon includes also two nitrite-responsive loci, nipAB (hcp-hcr) and nipC(dnrN), thus confirming the identity of the effector, i.e., nitrite. The proposed NsrR regulons in Neisseria and some other species are extended to include denitrification genes. As the

Dissimilatory metabolism of nitrogen oxides in bacteria: comparative reconstruction of transcriptional networks.

Directory of Open Access Journals (Sweden)

2005-10-01

Full Text Available Bacterial response to nitric oxide (NO is of major importance since NO is an obligatory intermediate of the nitrogen cycle. Transcriptional regulation of the dissimilatory nitric oxides metabolism in bacteria is diverse and involves FNR-like transcription factors HcpR, DNR, and NnrR; two-component systems NarXL and NarQP; NO-responsive activator NorR; and nitrite-sensitive repressor NsrR. Using comparative genomics approaches, we predict DNA-binding motifs for these transcriptional factors and describe corresponding regulons in available bacterial genomes. Within the FNR family of regulators, we observed a correlation of two specificity-determining amino acids and contacting bases in corresponding DNA recognition motif. Highly conserved regulon HcpR for the hybrid cluster protein and some other redox enzymes is present in diverse anaerobic bacteria, including Clostridia, Thermotogales, and delta-proteobacteria. NnrR and DNR control denitrification in alpha- and beta-proteobacteria, respectively. Sigma-54-dependent NorR regulon found in some gamma- and beta-proteobacteria contains various enzymes involved in the NO detoxification. Repressor NsrR, which was previously known to control only nitrite reductase operon in Nitrosomonas spp., appears to be the master regulator of the nitric oxides' metabolism, not only in most gamma- and beta-proteobacteria (including well-studied species such as Escherichia coli, but also in Gram-positive Bacillus and Streptomyces species. Positional analysis and comparison of regulatory regions of NO detoxification genes allows us to propose the candidate NsrR-binding motif. The most conserved member of the predicted NsrR regulon is the NO-detoxifying flavohemoglobin Hmp. In enterobacteria, the regulon also includes two nitrite-responsive loci, nipAB (hcp-hcr and nipC (dnrN, thus confirming the identity of the effector, i.e. nitrite. The proposed NsrR regulons in Neisseria and some other species are extended to include

Nitrogen fixation and molecular oxygen: comparative genomic reconstruction of transcription regulation in Alphaproteobacteria

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Olga V Tsoy

2016-08-01

Full Text Available Biological nitrogen fixation plays a crucial role in the nitrogen cycle. An ability to fix atmospheric nitrogen, reducing it to ammonium, was described for multiple species of Bacteria and Archaea. Being a complex and sensitive process, nitrogen fixation requires a complicated regulatory system, also, on the level of transcription. The transcriptional regulatory network for nitrogen fixation was extensively studied in several representatives of the class Alphaproteobacteria. This regulatory network includes the activator of nitrogen fixation NifA, working in tandem with the alternative sigma-factor RpoN as well as oxygen-responsive regulatory systems, one-component regulators FnrN/FixK and two-component system FixLJ. Here we used a comparative genomics analysis for in silico study of the transcriptional regulatory network in 50 genomes of Alphaproteobacteria. We extended the known regulons and proposed the scenario for the evolution of the nitrogen fixation transcriptional network. The reconstructed network substantially expands the existing knowledge of transcriptional regulation in nitrogen-fixing microorganisms and can be used for genetic experiments, metabolic reconstruction, and evolutionary analysis.

Frequency of BCR-ABL Transcript Types in Syrian CML Patients

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Sulaf Farhat-Maghribi

2016-01-01

Full Text Available Background. In Syria, CML patients are started on tyrosine kinase inhibitors (TKIs and monitored until complete molecular response is achieved. BCR-ABL mRNA transcript type is not routinely identified, contrary to the recommendations. In this study we aimed to identify the frequency of different BCR-ABL transcripts in Syrian CML patients and highlight their significance on monitoring and treatment protocols. Methods. CML patients positive for BCR-ABL transcripts by quantitative RT-PCR were enrolled. BCR-ABL transcript types were investigated using a home-made PCR method that was adapted from published protocols and optimized. The transcript types were then confirmed using a commercially available research kit. Results. Twenty-four transcripts were found in 21 patients. The most common was b2a2, followed by b3a2, b3a3, and e1a3 present solely in 12 (57.1%, 3 (14.3%, 2 (9.5%, and 1 (4.8%, respectively. Three samples (14.3% contained dual transcripts. While b3a2 transcript was apparently associated with warning molecular response to imatinib treatment, b2a2, b3a3, and e1a3 transcripts collectively proved otherwise (P=0.047. Conclusion. It might be advisable to identify the BCR-ABL transcript type in CML patients at diagnosis, using an empirically verified method, in order to link the detected transcript with the clinical findings, possible resistance to treatment, and appropriate monitoring methods.

Serum GGT activity and hsCRP level in patients with type 2 diabetes mellitus with good and poor glycemic control: An evidence linking oxidative stress, inflammation and glycemic control.

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Gohel, Mukesh G; Chacko, Anusha N

2013-12-20

Diabetes is undoubtedly one of the most challenging health problems in 21st century. Understanding the pathogenesis and preventing long term complications have been major goals of research in diabetes mellitus (DM). Research in the past few years has linked oxidative stress and inflammation to beta cell dysfunction. Aim of this study is to evaluate serum gamma-glutamyl transferase (GGT) activity (marker of oxidative stress) and high sensitivity C reactive protein (hsCRP) level (an inflammatory marker) in type 2 DM subjects with good and poor glycemic control. Further, we investigated correlation between serum GGT and hsCRP level with glycemic control (FBS, PP2BS, HbA1c) in subjects. A cross sectional study consists of 150 patients out of them 50 patients having type 2 DM with good control (Group II), 50 patients with type 2 DM with poor control (Group III) and 50 normal healthy control (Group I) were selected. Serum GGT, serum hsCRP, FBS, PP2BS, HbA1c, and other biochemical investigations include serum liver enzymes and lipids were measured. Mean serum GGT and hsCRP concentration were statistically significantly higher in group III patients compared to group I and group II subjects as well as increased in group II compared to group I (p stress and inflammation appears to be a key component and also associated with poor glycemic control and further pathogenesis of diabetes and its complications. All our finding suggesting a link between oxidative stress, inflammation and glycemic control in patient with type 2 diabetes mellitus.

Ultrasound and radionuclide images of liver. An IAEA (CRP) group study

International Nuclear Information System (INIS)

Fukuda, M.; Bergmann, H.; Padhy, A.K.; Fukuhisa, K.

1996-01-01

Liver diseases are many and vary widely in etiology and pathology. Pattern of liver diseases also vary depending on the geographical and demographical factors. Alcoholic cirrhosis is more common in industrialised countries whereas post necrotic or post hepatitic cirrhosis is more common in developing countries. Abscesses and parasitic cysts are more common in less privileged countries whereas cancer seems to be equally prevalent in all parts of the world. These differences in geographic pathology of liver diseases influence the education, training, learning process and skills of medical personnel who interpret liver images obtained from various imaging modalities. Thus the skills of liver image interpretation becomes an important variable which determines the ultimate value of a given imaging modality. In different countries, the training of nuclear medicine physicians vary in scope and content. The coordinated research programme (CRP), ''Evaluation of imaging procedures in the diagnosis of liver diseases (Phase II)'' endeavoured to address all these aspects mentioned above. This CRP was started in 1989 as a logical sequence to its predecessor, ''Evaluation of nuclear medicine procedures for the diagnosis of liver diseases''. Apart from Japan, nine other countries participated in the CRP. The objective of the CRP was to determine the sensitivity and specificity of the radiocolloid liver imaging and the standard grey scale ultrasound imaging of liver in different types of liver diseases with a view to determine the relative merit of each imaging modality in the diagnosis of a given type of liver disease. The intention was that if one shows distinctive superiority in term of its diagnostic value, then that modality can be recommended as a front line investigation in a given type of liver disease. This approach not only gives certain cost effectiveness in patient care, but also reduces demand on resources that are already under strain in developing countries

Mycobacterium tuberculosis cAMP Receptor Protein (Rv3676) Differs from the Escherichia coli Paradigm in Its cAMP Binding and DNA Binding Properties and Transcription Activation Properties*

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Stapleton, Melanie; Haq, Ihtshamul; Hunt, Debbie M.; Arnvig, Kristine B.; Artymiuk, Peter J.; Buxton, Roger S.; Green, Jeffrey

2010-01-01

The pathogen Mycobacterium tuberculosis produces a burst of cAMP upon infection of macrophages. Bacterial cyclic AMP receptor proteins (CRP) are transcription factors that respond to cAMP by binding at target promoters when cAMP concentrations increase. Rv3676 (CRPMt) is a CRP family protein that regulates expression of genes (rpfA and whiB1) that are potentially involved in M. tuberculosis persistence and/or emergence from the dormant state. Here, the CRPMt homodimer is shown to bind two molecules of cAMP (one per protomer) at noninteracting sites. Furthermore, cAMP binding by CRPMt was relatively weak, entropy driven, and resulted in a relatively small enhancement in DNA binding. Tandem CRPMt-binding sites (CRP1 at −58.5 and CRP2 at −37.5) were identified at the whiB1 promoter (PwhiB1). In vitro transcription reactions showed that CRP1 is an activating site and that CRP2, which was only occupied in the presence of cAMP or at high CRPMt concentrations in the absence of cAMP, is a repressing site. Binding of CRPMt to CRP1 was not essential for open complex formation but was required for transcription activation. Thus, these data suggest that binding of CRPMt to the PwhiB1 CRP1 site activates transcription at a step after open complex formation. In contrast, high cAMP concentrations allowed occupation of both CRP1 and CRP2 sites, resulting in inhibition of open complex formation. Thus, M. tuberculosis CRP has evolved several distinct characteristics, compared with the Escherichia coli CRP paradigm, to allow it to regulate gene expression against a background of high concentrations of cAMP. PMID:20028978

CRP in acute appendicitis--is it a necessary investigation?

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Amalesh, T; Shankar, M; Shankar, R

2004-01-01

Appendectomy is one of the commonest procedures in surgery. In spite of various investigations used to improve the accuracy of diagnosis, the rate of normal appendices removed is still about 15-30%. Many studies have investigated the role of C-reactive protein (CRP) in acute appendicitis, but with conflicting results. In a prospective, double blind study, blood for the measurement of serum C-reactive protein was collected pre-operatively from 192 children before going to the operating theatre for appendectomy. The histopathology was grouped into positive (acute appendicitis) and negative (normal appendix) and this was correlated with CRP values. CRP was normal in 14 out of 33 negative explorations (normal appendix on histopathology). The specificity and sensitivity of serum CRP was 42% and 91% respectively. The predictive value of a positive (raised CRP) and negative (normal CRP) test is 88% and 48% respectively. We conclude that neither raised nor normal CRP value is helpful in the diagnosis of acute appendicitis. CRP is not a good tool for helping the surgeon make the diagnosis of appendicitis and it should not be measured in suspected appendicitis.

Serum C-Reactive Protein (CRP), Target for Therapy or Trouble?

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Kraus, Virginia B; Jordan, Joanne M

2007-02-07

High sensitivity serum C-reactive protein (hs-CRP) has come into clinical use as a marker of risk for cardiovascular disease (CVD). In addition to a role as a marker of disease, CRP has also been implicated in the pathogenesis of CVD. Specific small-molecule inhibitors of CRP have recently been developed with the intent of mitigating cardiac damage during acute myocardial infarction. However, the use of CRP, both as a risk marker and a disease target are controversial for several reasons. Serum hs-CRP concentrations can be elevated on the basis of genetics, female gender, and non-Caucasian ethnicity. It is not clear, in these contexts, that elevations of hs-CRP have any pathological significance. As a non-specific indicator of inflammation, CRP is also not a specific indicator of a single disease state such as cardiovascular disease but elevated concentrations can be seen in association with other comorbidities including obesity and pulmonary disease. In sharp contrast to the proposed inhibition of CRP for cardiovascular disease treatment, the infusion of CRP has been shown to have profound therapeutic benefits for autoimmune disease and septic shock. The balance between the risks and benefits of these competing views of the role of CRP in disease and disease therapy is reminiscent of the ongoing controversy regarding the use of non-steroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal disease and their cardiovascular side effects. Soon, NSAIDs may not be the only agents about which Rheumatologists and Cardiologists may spar.

Serum C-Reactive Protein (CRP, Target for Therapy or Trouble?

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Virginia B. Kraus

2006-01-01

Full Text Available High sensitivity serum C-reactive protein (hs-CRP has come into clinical use as a marker of risk for cardiovascular disease (CVD. In addition to a role as a marker of disease, CRP has also been implicated in the pathogenesis of CVD. Specific small-molecule inhibitors of CRP have recently been developed with the intent of mitigating cardiac damage during acute myocardial infarction. However, the use of CRP, both as a risk marker and a disease target are controversial for several reasons. Serum hs-CRP concentrations can be elevated on the basis of genetics, female gender, and non-Caucasian ethnicity. It is not clear, in these contexts, that elevations of hs-CRP have any pathological significance. As a non-specific indicator of inflammation, CRP is also not a specific indicator of a single disease state such as cardiovascular disease but elevated concentrations can be seen in association with other comorbidities including obesity and pulmonary disease. In sharp contrast to the proposed inhibition of CRP for cardiovascular disease treatment, the infusion of CRP has been shown to have profound therapeutic benefits for autoimmune disease and septic shock. The balance between the risks and benefits of these competing views of the role of CRP in disease and disease therapy is reminiscent of the ongoing controversy regarding the use of non-steroidal anti-inflammatory drugs (NSAIDs for musculoskeletal disease and their cardiovascular side effects. Soon, NSAIDs may not be the only agents about which Rheumatologists and Cardiologists may spar.

Tumor necrosis factor (TNF-alpha) and C-reactive protein (CRP) are positively associated with the risk of chronic kidney disease in patients with type 2 diabetes.

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Yeo, Eun-Sil; Hwang, Ji-Yun; Park, Ji Eun; Choi, Young Ju; Huh, Kap Bum; Kim, Wha Young

2010-07-01

Chronic low-grade inflammation may induce chronic kidney disease in patients with type 2 diabetes. This study investigated the relation between inflammatory biomarkers and chronic kidney disease in patients with type 2 diabetes, which has not yet been reported in Asian populations. A cross-sectional study was performed in 543 patients recruited from diabetic clinics for an ongoing, prospective study. Multivariate logistic regression was used to evaluate the association between inflammatory biomarkers and the presence of chronic kidney disease (estimated glomerular filtration rate Disease equation using plasma creatinine). The risk of chronic kidney disease increased in the highest quartiles of C-reactive protein (CRP) [multivariate odds ratio (OR) = 3.73; 95% CI = 1.19-1.70] and tumor necrosis factor-alpha (multivariate OR = 4.45; 95% CI = 1.63-12.11) compared to the lowest quartiles after adjustments for age, sex, zinc intake, and other putative risk factors for chronic kidney disease. Our results suggest that CRP and tumor necrosis factor-alpha may be independent risk factors for chronic kidney disease in patients with type 2 diabetes. A causal mechanism of this association should be evaluated in a followup study of Korean patients with type 2 diabetes.

Cell type-specific termination of transcription by transposable element sequences.

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Conley, Andrew B; Jordan, I King

2012-09-30

Transposable elements (TEs) encode sequences necessary for their own transposition, including signals required for the termination of transcription. TE sequences within the introns of human genes show an antisense orientation bias, which has been proposed to reflect selection against TE sequences in the sense orientation owing to their ability to terminate the transcription of host gene transcripts. While there is evidence in support of this model for some elements, the extent to which TE sequences actually terminate transcription of human gene across the genome remains an open question. Using high-throughput sequencing data, we have characterized over 9,000 distinct TE-derived sequences that provide transcription termination sites for 5,747 human genes across eight different cell types. Rarefaction curve analysis suggests that there may be twice as many TE-derived termination sites (TE-TTS) genome-wide among all human cell types. The local chromatin environment for these TE-TTS is similar to that seen for 3' UTR canonical TTS and distinct from the chromatin environment of other intragenic TE sequences. However, those TE-TTS located within the introns of human genes were found to be far more cell type-specific than the canonical TTS. TE-TTS were much more likely to be found in the sense orientation than other intragenic TE sequences of the same TE family and TE-TTS in the sense orientation terminate transcription more efficiently than those found in the antisense orientation. Alu sequences were found to provide a large number of relatively weak TTS, whereas LTR elements provided a smaller number of much stronger TTS. TE sequences provide numerous termination sites to human genes, and TE-derived TTS are particularly cell type-specific. Thus, TE sequences provide a powerful mechanism for the diversification of transcriptional profiles between cell types and among evolutionary lineages, since most TE-TTS are evolutionarily young. The extent of transcription

Prospective associations of C-reactive protein (CRP) levels and CRP genetic risk scores with risk of total knee and hip replacement for osteoarthritis in a diverse cohort.

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Shadyab, A H; Terkeltaub, R; Kooperberg, C; Reiner, A; Eaton, C B; Jackson, R D; Krok-Schoen, J L; Salem, R M; LaCroix, A Z

2018-05-22

To examine associations of high-sensitivity C-reactive protein (CRP) levels and polygenic CRP genetic risk scores (GRS) with risk of end-stage hip or knee osteoarthritis (OA), defined as incident total hip (THR) or knee replacement (TKR) for OA. This study included a cohort of postmenopausal white, African American, and Hispanic women from the Women's Health Initiative. Women were followed from baseline to date of THR or TKR, death, or December 31, 2014. Medicare claims data identified THR and TKR. Hs-CRP and genotyping data were collected at baseline. Three CRP GRS were constructed: 1) a 4-SNP GRS comprised of genetic variants representing variation in the CRP gene among European populations; 2) a multilocus 18-SNP GRS of genetic variants significantly associated with CRP levels in a meta-analysis of genome-wide association studies; and 3) a 5-SNP GRS of genetic variants significantly associated with CRP levels among African American women. In analyses conducted separately among each race and ethnic group, there were no significant associations of ln hs-CRP with risk of THR or TKR, after adjusting for age, body mass index, lifestyle characteristics, chronic diseases, hormone therapy use, and non-steroidal anti-inflammatory drug use. CRP GRS were not associated with risk of THR or TKR in any ethnic group. Serum levels of ln hs-CRP and genetically-predicted CRP levels were not associated with risk of THR or TKR for OA among a diverse cohort of women. Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Cell type-specific termination of transcription by transposable element sequences

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Conley Andrew B

2012-09-01

Full Text Available Abstract Background Transposable elements (TEs encode sequences necessary for their own transposition, including signals required for the termination of transcription. TE sequences within the introns of human genes show an antisense orientation bias, which has been proposed to reflect selection against TE sequences in the sense orientation owing to their ability to terminate the transcription of host gene transcripts. While there is evidence in support of this model for some elements, the extent to which TE sequences actually terminate transcription of human gene across the genome remains an open question. Results Using high-throughput sequencing data, we have characterized over 9,000 distinct TE-derived sequences that provide transcription termination sites for 5,747 human genes across eight different cell types. Rarefaction curve analysis suggests that there may be twice as many TE-derived termination sites (TE-TTS genome-wide among all human cell types. The local chromatin environment for these TE-TTS is similar to that seen for 3′ UTR canonical TTS and distinct from the chromatin environment of other intragenic TE sequences. However, those TE-TTS located within the introns of human genes were found to be far more cell type-specific than the canonical TTS. TE-TTS were much more likely to be found in the sense orientation than other intragenic TE sequences of the same TE family and TE-TTS in the sense orientation terminate transcription more efficiently than those found in the antisense orientation. Alu sequences were found to provide a large number of relatively weak TTS, whereas LTR elements provided a smaller number of much stronger TTS. Conclusions TE sequences provide numerous termination sites to human genes, and TE-derived TTS are particularly cell type-specific. Thus, TE sequences provide a powerful mechanism for the diversification of transcriptional profiles between cell types and among evolutionary lineages, since most TE-TTS are

Characterization of a crp* mutant of the E. coli cAMP receptor protein

International Nuclear Information System (INIS)

Ren, Y.L.; Garges, S.; Adhya, S.; Krakow, J.S.

1987-01-01

One of the crp* mutants previously isolated to activate lac promoter in vivo has been characterized with regard to its biochemical properties. CRP*592 shows a more open conformation than CRP as indicated by its sensitivity to proteolytic attack. Dithionitrobenzoic acid mediated intersubunit crosslinking of CRP requires cAMP; this reaction occurs with unliganded CRP*592. Binding of CRP to its site on the lac promoter and activation of abortive initiation is effected by cAMP but not by cGMP. CRP*592 can activate abortive initiation in the presence of cAMP or cGMP and also at a high CRP*592 concentration in the absence of cyclic nucleotide. DNase I footprinting shows that cAMP-CRP* binds to its site on lac P + while unliganded CRP* and cGMP-CRP* form a stable complex with the [ 32 P]lac P + only in the presence of RNA polymerase. While cGMP binds to CRP it cannot replace cAMP in effecting the conformation necessary for site specific promoter binding; the weakly active unliganded CRP*592 can be shifted to a functional conformation by cAMP, cGMP and RNA polymerase

Study on the changes of serum adiponectin (APN), insulin, C-reactive protein (CRP) and leptin levels after one year treatment in patients with type 2 diabetes

International Nuclear Information System (INIS)

Du Tongxin; Wang Zizheng; Wang Shukui; Li Yan; Fu Lei; Lin Yanli; Qu Wei; Qi Shaokang; Tao Xiaojun

2005-01-01

Objective: To investigate the β-cell function status and possible mechanism of insulin resistance in patients with type 2 diabetes through studies on the changes of serum APN, insulin, CRP, leptin, insulin antibody and glutamic acid decarboxylase antibody (GAD-Ab) levels after one year of treatment. Methods: Serum levels of the above four parameters and the positive rate of the two antibodies were measured (with CLIA, ELISA and RIA as appropriately) in 184 patients with type 2 diabetes and 30 controls as well as in 75 patients after one year of treatment. Results: The serum contents of insulin, leptin, CRP, insulin antibody in patients with type 2 diabetes were significantly higher (P<0.01) and APN levels significantly lower (P<0.001) than those in controls. Levels of APN were negatively correlated with those of the other parameters. In the 75 treated patients, levels of those parameters (with the exception of APN and insulin-antibody) decreased significantly. However, the APN levels were significantly increased (vs before treatment, P<0.001). Conclusion: Further study on the dynamic changes of these parameters in the diabetic patients might elucidate certain key-points in the pathogenesis of the disease. (authors)

Pre-steady-state kinetic studies of redox reactions catalysed by Bacillus subtilis ferredoxin-NADP(+) oxidoreductase with NADP(+)/NADPH and ferredoxin.

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Seo, Daisuke; Soeta, Takahiro; Sakurai, Hidehiro; Sétif, Pierre; Sakurai, Takeshi

2016-06-01

Ferredoxin-NADP(+) oxidoreductase ([EC1.18.1.2], FNR) from Bacillus subtilis (BsFNR) is a homodimeric flavoprotein sharing structural homology with bacterial NADPH-thioredoxin reductase. Pre-steady-state kinetics of the reactions of BsFNR with NADP(+), NADPH, NADPD (deuterated form) and B. subtilis ferredoxin (BsFd) using stopped-flow spectrophotometry were studied. Mixing BsFNR with NADP(+) and NADPH yielded two types of charge-transfer (CT) complexes, oxidized FNR (FNR(ox))-NADPH and reduced FNR (FNR(red))-NADP(+), both having CT absorption bands centered at approximately 600n m. After mixing BsFNR(ox) with about a 10-fold molar excess of NADPH (forward reaction), BsFNR was almost completely reduced at equilibrium. When BsFNR(red) was mixed with NADP(+), the amount of BsFNR(ox) increased with increasing NADP(+) concentration, but BsFNR(red) remained as the major species at equilibrium even with about 50-fold molar excess NADP(+). In both directions, the hydride-transfer was the rate-determining step, where the forward direction rate constant (~500 s(-1)) was much higher than the reverse one (reaction. The characteristics of the BsFNR reactions with NADP(+)/NADPH were compared with those of other types of FNRs. Copyright © 2016 Elsevier B.V. All rights reserved.

Lipids, atherosclerosis and CVD risk: is CRP an innocent bystander?

DEFF Research Database (Denmark)

Nordestgaard, B G; Zacho, J

2009-01-01

AIM: To evaluate recent human studies with respect to the interpretation of whether elevated plasma levels of C-reactive protein (CRP) cause cardiovascular disease (CVD), or whether elevated CRP levels more likely is an innocent bystander. DATA SYNTHESIS: Elevated CRP concentrations...... and vulnerability of atherosclerotic plaques, and thus simply an innocent bystander in CVD....

Cancer-type dependent expression of CK2 transcripts.

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Melissa M J Chua

Full Text Available A multitude of proteins are aberrantly expressed in cancer cells, including the oncogenic serine-threonine kinase CK2. In a previous report, we found increases in CK2 transcript expression that could explain the increased CK2 protein levels found in tumors from lung and bronchus, prostate, breast, colon and rectum, ovarian and pancreatic cancers. We also found that, contrary to the current notions about CK2, some CK2 transcripts were downregulated in several cancers. Here, we investigate all other cancers using Oncomine to determine whether they also display significant CK2 transcript dysregulation. As anticipated from our previous analysis, we found cancers with all CK2 transcripts upregulated (e.g. cervical, and cancers where there was a combination of upregulation and/or downregulation of the CK2 transcripts (e.g. sarcoma. Unexpectedly, we found some cancers with significant downregulation of all CK2 transcripts (e.g. testicular cancer. We also found that, in some cases, CK2 transcript levels were already dysregulated in benign lesions (e.g. Barrett's esophagus. We also found that CK2 transcript upregulation correlated with lower patient survival in most cases where data was significant. However, there were two cancer types, glioblastoma and renal cell carcinoma, where CK2 transcript upregulation correlated with higher survival. Overall, these data show that the expression levels of CK2 genes is highly variable in cancers and can lead to different patient outcomes.

PHB Biosynthesis Counteracts Redox Stress in Herbaspirillum seropedicae

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Marcelo B. Batista

2018-03-01

Full Text Available The ability of bacteria to produce polyhydroxyalkanoates such as poly(3-hydroxybutyrate (PHB enables provision of a carbon storage molecule that can be mobilized under demanding physiological conditions. However, the precise function of PHB in cellular metabolism has not been clearly defined. In order to determine the impact of PHB production on global physiology, we have characterized the properties of a ΔphaC1 mutant strain of the diazotrophic bacterium Herbaspirillum seropedicae. The absence of PHB in the mutant strain not only perturbs redox balance and increases oxidative stress, but also influences the activity of the redox-sensing Fnr transcription regulators, resulting in significant changes in expression of the cytochrome c-branch of the electron transport chain. The synthesis of PHB is itself dependent on the Fnr1 and Fnr3 proteins resulting in a cyclic dependency that couples synthesis of PHB with redox regulation. Transcriptional profiling of the ΔphaC1 mutant reveals that the loss of PHB synthesis affects the expression of many genes, including approximately 30% of the Fnr regulon.

PHB Biosynthesis Counteracts Redox Stress in Herbaspirillum seropedicae.

Science.gov (United States)

Batista, Marcelo B; Teixeira, Cícero S; Sfeir, Michelle Z T; Alves, Luis P S; Valdameri, Glaucio; Pedrosa, Fabio de Oliveira; Sassaki, Guilherme L; Steffens, Maria B R; de Souza, Emanuel M; Dixon, Ray; Müller-Santos, Marcelo

2018-01-01

The ability of bacteria to produce polyhydroxyalkanoates such as poly(3-hydroxybutyrate) (PHB) enables provision of a carbon storage molecule that can be mobilized under demanding physiological conditions. However, the precise function of PHB in cellular metabolism has not been clearly defined. In order to determine the impact of PHB production on global physiology, we have characterized the properties of a Δ phaC1 mutant strain of the diazotrophic bacterium Herbaspirillum seropedicae . The absence of PHB in the mutant strain not only perturbs redox balance and increases oxidative stress, but also influences the activity of the redox-sensing Fnr transcription regulators, resulting in significant changes in expression of the cytochrome c -branch of the electron transport chain. The synthesis of PHB is itself dependent on the Fnr1 and Fnr3 proteins resulting in a cyclic dependency that couples synthesis of PHB with redox regulation. Transcriptional profiling of the Δ phaC1 mutant reveals that the loss of PHB synthesis affects the expression of many genes, including approximately 30% of the Fnr regulon.

Three transcription regulators of the Nss family mediate the adaptive response induced by nitrate, nitric oxide or nitrous oxide in Wolinella succinogenes.

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Kern, Melanie; Simon, Jörg

2016-09-01

Sensing potential nitrogen-containing respiratory substrates such as nitrate, nitrite, hydroxylamine, nitric oxide (NO) or nitrous oxide (N2 O) in the environment and subsequent upregulation of corresponding catabolic enzymes is essential for many microbial cells. The molecular mechanisms of such adaptive responses are, however, highly diverse in different species. Here, induction of periplasmic nitrate reductase (Nap), cytochrome c nitrite reductase (Nrf) and cytochrome c N2 O reductase (cNos) was investigated in cells of the Epsilonproteobacterium Wolinella succinogenes grown either by fumarate, nitrate or N2 O respiration. Furthermore, fumarate respiration in the presence of various nitrogen compounds or NO-releasing chemicals was examined. Upregulation of each of the Nap, Nrf and cNos enzyme systems was found in response to the presence of nitrate, NO-releasers or N2 O, and the cells were shown to employ three transcription regulators of the Crp-Fnr superfamily (homologues of Campylobacter jejuni NssR), designated NssA, NssB and NssC, to mediate the upregulation of Nap, Nrf and cNos. Analysis of single nss mutants revealed that NssA controls production of the Nap and Nrf systems in fumarate-grown cells, while NssB was required to induce the Nap, Nrf and cNos systems specifically in response to NO-generators. NssC was indispensable for cNos production under any tested condition. The data indicate dedicated signal transduction routes responsive to nitrate, NO and N2 O and imply the presence of an N2 O-sensing mechanism. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes

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Thanabalasingham, G.; Shah, N.; Vaxillaire, M.

2011-01-01

CRP) levels are lower in UK patients with hepatocyte nuclear factor 1 alpha (HNF1A)-MODY than in other diabetes subtypes. In this large multi-centre study we aimed to assess the clinical validity of hsCRP as a diagnostic biomarker, examine the genotype-phenotype relationship and compare different hsCRP assays....... High-sensitivity CRP levels were analysed in individuals with HNF1A-MODY (n = 457), glucokinase (GCK)-MODY (n = 404), hepatocyte nuclear factor 4 alpha (HNF4A)-MODY (n = 54) and type 2 diabetes (n = 582) from seven European centres. Three common assays for hsCRP analysis were evaluated. We excluded 121......) a parts per thousand yenaEuro parts per thousand 0.91, p a parts per thousand currency signaEuro parts per thousand 1 x 10(-5)). Across the seven centres, the C-statistic for distinguishing HNF1A-MODY from young adult-onset type 2 diabetes ranged from 0.79 to 0.97, indicating high discriminative accuracy...

C-Reactive Protein (CRP) Test

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... can be caused by a number of different pathological conditions such as arthritis , lupus , or inflammatory bowel ... clinchem.org . Accessed October 2011. Lowry, F. (2010 March 23). CRP Test Guides Antibiotic Prescribing for Respiratory ...

Evaluation of serum homocysteine, high-sensitivity CRP, and RBC folate in patients with alopecia areata

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Maryam Yousefi

2014-01-01

Full Text Available Introduction: Alopecia areata (AA is a common type of hair loss with an autoimmune basis. As the role of homocysteine (Hcys, folate, and CRP has been considered in some autoimmune diseases. Objectives: To evaluate homocysteine, folate and CRP level in AA. Methods: This study was performed on 29 patients who had AA for at least 6 months affecting more than 20% of scalp, and 32 healthy controls. Levels of serum Hcys, blood high-sensitivity CRP, and RBC folate were measured in all subjects. Results: The mean level of RBC folate was significantly lower in the patient group than that in controls (P < 0.001. Also, the level of RBC folate was significantly lower in patients with extensive forms of disease (alopecia totalis/alopecia universalis in comparison with more localized form (patchy hair loss (P < 0.05. Patients with higher "Severity of Alopecia Total" (SALT score had lower RBC folate, as well. Serum Hcys and blood high-sensitivity CRP levels did not show a significant difference in two groups. Conclusion: Patients with alopecia areata have lower level of RBC folate which is in negative correlation with both severity and extension of AA.

Correlation of CRP, fasting serum triglycerides and obesity as cardiovascular risk factors.

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Firdous, Samar

2014-05-01

To determine the correlation of C-reactive protein (CRP) with fasting triglycerides (TG) among pre-obese and obese patients without established diagnosis of coronary artery disease (CAD). A comparative cross-sectional study. Mayo Hospital, Lahore, from January to June 2010. Patients with BMI > 23 kg/m2 aged between 18 - 65 years were inducted and above variables were studied. Patients with signs of fluid retention, collagen vascular disease, CAD, patients on corticosteroids, immunomodulators or lipid lowering medications and febrile patients were not recruited. Body mass index was also determined. Independent sample t-test was applied to see the mean difference of age, CRP level and triglycerides level in relation to gender. Chi-square test was used to see the association between qualitative variables. ANOVA was applied to see CRP and fasting serum TG level in relation to BMI categories. Pearson correlation and simple linear regression was applied to see the dependency of CRP and triglycerides with BMI. P-value ² 0.05 was taken as significant. Raised CRP was major finding among all groups of BMI. Most of obese and pre-obese patients were young and middle aged and belonged to pre-obese group followed by class-1 and class-2 obesity. CRP level increased with body mass index. No such trend was observed for triglycerides. There was an intermediate positive correlation between CRP and BMI and triglycerides and BMI showed a weak negative correlation. If BMI increases by 1 unit on the average, CRP rises by 0.239 times and this unit rise was significant. Whereas 1 unit rise increase in triglycerides on the average cause CRP to decrease -0.006 times but this value was insignificant. Raised CRP and high fasting TG were major findings in all age groups especially among young and middle aged people. Obesity, hypertriglyceridemia and raised CRP are interrelated suggesting that obesity is not only linked to hypertriglyceridemia but vascular inflammation among pre-obese and obese

Clinical Significance of Determination of the Serum Levels of NT-proBNP and hs-CRP in Patients with Acute Coronary Syndrome

International Nuclear Information System (INIS)

Zheng Zhaojun; Zheng Jing; Sun Weili; Yuan Yuan; Tao Jian; Li Weipeng

2010-01-01

To explore the clinical significance the serum levels of N-Terminal proB-Type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) in patients with acute coronary syndrome,the serum levels of NT-proBNP and hs-CRP in patients and normal controls were determined by ECi Immunity Analyzer and radioimmunoassay respectively. The results showed that the serum levels of NT-proBNP and hs-CRP in patients with acute coronary syndrome were significantly higher than that of controls (P<0.05). The diagnostic specificity for acute coronary syndrome was 100% by combined detection of NT-proBNP and hs-CRP. The results suggest that the combined detection of serum NT-proBNP and hs-CRP levels are very important to evaluate heart function in patients with acute coronary syndrome. (authors)

Correlation of CRP, Fasting Serum Triglycerides and Obesity as Cardiovascular Risk Factors

International Nuclear Information System (INIS)

Firdous, S.

2014-01-01

Objective: To determine the correlation of C-reactive protein (CRP) with fasting triglycerides (TG) among pre-obese and obese patients without established diagnosis of coronary artery disease (CAD). Study Design: A comparative cross-sectional study. Place and Duration of Study: Mayo Hospital, Lahore, from January to June 2010. Methodology: Patients with BMI > 23 kg/m2 aged between 18 - 65 years were inducted and above variables were studied. Patients with signs of fluid retention, collagen vascular disease, CAD, patients on corticosteroids, immunomodulators or lipid lowering medications and febrile patients were not recruited. Body mass index was also determined. Independent sample t-test was applied to see the mean difference of age, CRP level and triglycerides level in relation to gender. Chisquare test was used to see the association between qualitative variables. ANOVA was applied to see CRP and fasting serum TG level in relation to BMI categories. Pearson correlation and simple linear regression was applied to see the dependency of CRP and triglycerides with BMI. P-value A = 0.05 was taken as significant. Results: Raised CRP was major finding among all groups of BMI. Most of obese and pre-obese patients were young and middle aged and belonged to pre-obese group followed by class-1 and class-2 obesity. CRP level increased with body mass index. No such trend was observed for triglycerides. There was an intermediate positive correlation between CRP and BMI and triglycerides and BMI showed a weak negative correlation. If BMI increases by 1 unit on the average, CRP rises by 0.239 times and this unit rise was significant. Whereas 1 unit rise increase in triglycerides on the average cause CRP to decrease -0.006 times but this value was insignificant. Conclusion: Raised CRP and high fasting TG were major findings in all age groups especially among young and middle aged people. Obesity, hypertriglyceridemia and raised CRP are interrelated suggesting that obesity is not

A-type nuclear lamins act as transcriptional repressors when targeted to promoters

International Nuclear Information System (INIS)

Lee, Damian C.; Welton, K. Linnea; Smith, Erica D.; Kennedy, Brian K.

2009-01-01

Regions of heterochromatin are often found at the periphery of the mammalian nucleus, juxtaposed to the nuclear lamina. Genes in these regions are likely maintained in a transcriptionally silent state, although other locations at the nuclear periphery associated with nuclear pores are sites of active transcription. As primary components of the nuclear lamina, A- and B-type nuclear lamins are intermediate filament proteins that interact with DNA, histones and known transcriptional repressors, leading to speculation that they may promote establishment of repressive domains. However, no direct evidence of a role for nuclear lamins in transcriptional repression has been reported. Here we find that human lamin A, when expressed in yeast and cultured human cells as a fusion protein to the Gal4 DNA-binding domain (DBD), can mediate robust transcriptional repression of promoters with Gal4 binding sites. Full repression by lamin A requires both the coiled-coil rod domain and the C-terminal tail domain. In human cells, other intermediate filament proteins such as lamin B and vimentin are unable to confer robust repression as Gal4-DBD fusions, indicating that this property is specific to A-type nuclear lamins. These findings indicate that A-type lamins can promote transcriptional repression when in proximity of a promoter

Nucleotide sequences of cDNAs for human papillomavirus type 18 transcripts in HeLa cells

International Nuclear Information System (INIS)

Inagaki, Yutaka; Tsunokawa, Youko; Takebe, Naoko; Terada, Masaaki; Sugimura, Takashi; Nawa, Hiroyuki; Nakanishi, Shigetada

1988-01-01

HeLa cells expressed 3.4- and 1.6-kilobase (kb) transcripts of the integrated human papillomavirus (HPV) type 18 genome. Two types of cDNA clones representing each size of HPV type 18 transcript were isolated. Sequence analysis of these two types of cDNA clones revealed that the 3.4-kb transcript contained E6, E7, the 5' portion of E1, and human sequence and that the 1.6-kb transcript contained spliced and frameshifted E6 (E6 * ), E7, and human sequence. There was a common human sequence containing a poly(A) addition signal in the 3' end portions of both transcripts, indicating that they were transcribed from the HPV genome at the same integration site with different splicing. Furthermore, the 1.6-kb transcript contained both of the two viral TATA boxes upstream of E6, strongly indicating that a cellular promoter was used for its transcription

IAEA/CRP for decommissioning techniques for research reactors

Energy Technology Data Exchange (ETDEWEB)

Oh, Won Zin; Won, H. J.; Kim, K. N.; Lee, K. W.; Jung, C. H

2001-03-01

The following were studied through the project entitled 'IAEA/CRP for decommissioning techniques for research reactors 1. Decontamination technology development for TRIGA radioactive soil waste - Electrokinetic soil decontamination experimental results and its mathematical simulation 2. The 2nd IAEA/CRP for decommissioning techniques for research reactors - Meeting results and program 3. Hosting the 2001 IAEA/RCA D and D training course for research reactors and small nuclear facilities.

IAEA/CRP for decommissioning techniques for research reactors

International Nuclear Information System (INIS)

Oh, Won Zin; Won, H. J.; Kim, K. N.; Lee, K. W.; Jung, C. H.

2001-03-01

The following were studied through the project entitled 'IAEA/CRP for decommissioning techniques for research reactors 1. Decontamination technology development for TRIGA radioactive soil waste - Electrokinetic soil decontamination experimental results and its mathematical simulation 2. The 2nd IAEA/CRP for decommissioning techniques for research reactors - Meeting results and program 3. Hosting the 2001 IAEA/RCA D and D training course for research reactors and small nuclear facilities

Circulating Level of Serum Chemerin and CRP in ‎Type 2 Diabetes Mellitus Patients with and ‎Without Hypertension in Menopauses Women

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Hussein Jasim AL-Harbi

2017-12-01

Full Text Available Chemerin may play a role in connecting inflammation and metabolic syndrome(MS, C-reactive protein(CRP level is markedly rising during infectious and inflammatory diseases . The aimed of this study to evaluate both  C- reactive protein  (CRP  and Chemerin as  subclinical markers in diabetic patients women. A total of 90 women, including, 24 healthy women (as control group, 66 women patients with  diabetes mellitus type 2 (T2DM (22diabetics with hypertension, 22 diabetics without hypertension and 22 hypertension only,there ages ranged between49-64 years. The result showed that  significant increase (p≤0.05 in mean chemerin level in the diabetes group (8.766 ±0.648 ng/ml in comparison with control group( 4.042±0.320 ng/ml. Also, the result, revealed that significant increase (P<0.05 in the level of chemerin in women suffering from hypertension and diabetes  (14.108 ± 0.577 ng/ml in comparison to the women suffering from diabetic  only which reached (8.766 ± 0.648 ng/ml. The data pointed out that the serum CRP level significant increase in T2DM group (6.176±0.1905 compared with control group (2.20±0.15 ng/ml . Also, the result revealed that significant increase (P<0.05 of the CRP level with hypertension women patients (4.45 ± 0.131ng/ml compared with the control group( 2.20±0.15 ng/ml and significant increase(P<0.05 in diabetic with hypertension women group patients comparison with the women suffering from diabetic  only. The chemerin and C-RP  in hypertensive and normotensive patients with T2DM may be play an important role in activation of Immune Response in these patients

Circulating Level of Serum Chemerin and CRP in ‎Type 2 Diabetes Mellitus Patients with and ‎Without Hypertension in Menopauses Women

Directory of Open Access Journals (Sweden)

Hussein Jasim AL-Harbi

2018-01-01

Full Text Available Chemerin may play a role in connecting inflammation and metabolic syndrome(MS, C-reactive protein(CRP level is markedly rising during infectious and inflammatory diseases . The aimed of this study to evaluate both  C- reactive protein  (CRP  and Chemerin as  subclinical markers in diabetic patients women. A total of 90 women, including, 24 healthy women (as control group, 66 women patients with  diabetes mellitus type 2 (T2DM (22diabetics with hypertension, 22 diabetics without hypertension and 22 hypertension only,there ages ranged between49-64 years. The result showed that  significant increase (p≤0.05 in mean chemerin level in the diabetes group (8.766 ±0.648 ng/ml in comparison with control group( 4.042±0.320 ng/ml. Also, the result, revealed that significant increase (P<0.05 in the level of chemerin in women suffering from hypertension and diabetes  (14.108 ± 0.577 ng/ml in comparison to the women suffering from diabetic  only which reached (8.766 ± 0.648 ng/ml. The data pointed out that the serum CRP level significant increase in T2DM group (6.176±0.1905 compared with control group (2.20±0.15 ng/ml . Also, the result revealed that significant increase (P<0.05 of the CRP level with hypertension women patients (4.45 ± 0.131ng/ml compared with the control group( 2.20±0.15 ng/ml and significant increase(P<0.05 in diabetic with hypertension women group patients comparison with the women suffering from diabetic  only. The chemerin and C-RP  in hypertensive and normotensive patients with T2DM may be play an important role in activation of Immune Response in these patients .

Relationship of HS CRP and Sacroiliac Joint Inflammation in Undifferentiated Spondyloarthritis.

Science.gov (United States)

Liu, Te-Jung; Chang, Cheng-Chiang; Chen, Liang-Cheng; Chu, Heng-Yi; Hsu, Chun-Sheng; Chang, Shin-Tsu

2018-01-01

Elevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA). In this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement. A total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson's correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA.

Relationship of HS CRP and Sacroiliac Joint Inflammation in Undifferentiated Spondyloarthritis

Science.gov (United States)

Liu, Te-Jung; Chang, Cheng-Chiang; Chen, Liang-Cheng; Chu, Heng-Yi; Hsu, Chun-Sheng; Chang, Shin-Tsu

2018-01-01

Abstract Objective Elevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA). Methods In this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement. Results A total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson’s correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA. PMID:29785410

Correlation of Progranulin, Granulin, Adiponectin and Vaspin with Metaflammation (hs-CRP in Indonesian Obese Men

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Rosalia E Napitupulu

2013-08-01

Full Text Available BACKGROUND: Obesity is closely related to chronic, low grade systemic inflammation (metaflammation and it leads to further metabolic complications such as hypertension, atherosclerosis, and type 2 diabetes due to the adipocytokine imbalance. This study was carried out to assess the correlation between progranulin, granulin, adiponectin and visceral adipose tissue-derived serine protease inhibitor (Vaspin with metaflammation (high sensitivity C-reactive protein (hs-CRP in centrally obese men. METHODS: This study was observational with a cross sectional design involving 60 men aged 30-60 years, consisted of 43 obese men (waist circumference (WC ≥90 cm and 13 non obese men (WC 105 cm. CONCLUSIONS: We found metaflammation (hs-CRP was significantly correlated with Vaspin, but not with progranulin, granulin and adiponectin, in obese men. We suggest the possibility of a dynamic expression of adipokines related to WC that are subjected to adipocytes hypertrophy-hyperplasia phenomenon. KEYWORDS: progranulin, granulin, adiponectin, Vaspin, hs-CRP, metaflammation, central obesity.

Serum hsCRP: A Novel Marker for Prediction of Cerebrovascular Accidents (Stroke).

Science.gov (United States)

Patgiri, Dibyaratna; Pathak, Mauchumi Saikia; Sharma, Pradeep; Kutum, Tridip; Mattack, Nirmali

2014-12-01

Strokes are caused by disruption of the blood supply to the brain. This may result from either blockage or rupture of a blood vessel. Yearly 15 million people worldwide suffer a stroke. India ranks second worldwide in terms of deaths from stroke. The incidence of stroke increases with age affecting the economically productive middle aged population. Hypertension and male sex are other risk factors for stroke. C-Reactive Protein (CRP) is an acute phase protein whose concentration rises in blood following inflammation. Formerly, assays for CRP detected its rise only after significant inflammation. However, recently developed high sensitivity assays (hsCRP) enable the measurement of CRP in individuals who are apparently healthy. Several studies indicate that hsCRP is elevated in individuals who are at risk of developing Coronary Artery Disease or Cerebrovascular events, the elevation may be found years before the first detection of vascular problems. In the absence of other biochemical markers, the present study aimed to evaluate the predictive and diagnostic role of hsCRP in stroke. The study consisted of 50 patients of acute stroke admitted in Gauhati Medical College and Hospital. The control population consisted of two groups - 50 age and sex matched controls with hypertension (Hypertensive control group) and 50 age and sex matched controls with no obvious disease constituted the Normal control group. hsCRP levels were measured in all the groups and compared statistically. hsCRP is an acute phase reactant whose concentration rises in stroke as well as in those at risk. The rise may be identified even before the appearance of risk factors. Hence, hsCRP may be useful as a predictive and diagnostic marker in stroke.

Study on the strategy of participation in CRP and effective technical cooperation with the IAEA

International Nuclear Information System (INIS)

Kim, Myung Ro; Choi, P. H.; Kim, K. P.; Shim, J. S.; Shim, M. W.; Min, D.Y.

2003-07-01

This project aims to promote the participation from Korea in the IAEA CRP, and provide the CRP projects being undertaken in Korea with R and D funds. In order to achieve these goals, this project supported 24 CRP projects with 50,000,000 won in total. In addition, an analysis on the IAEA CRP announcement for 2003 was undertaken by this project, and promoted participation in the the CRP. As a result, 29 new CRP proposals for 2003 were submitted to the IAEA Finally, some recommendations on the CRP strategy of Korea were proposed

High CRP values predict poor survival in patients with penile cancer

International Nuclear Information System (INIS)

Steffens, Sandra; Kuczyk, Markus A; Schrader, Andres J; Al Ghazal, Andreas; Steinestel, Julie; Lehmann, Rieke; Wegener, Gerd; Schnoeller, Thomas J; Cronauer, Marcus V; Jentzmik, Florian; Schrader, Mark

2013-01-01

High levels of circulating C-reactive protein (CRP) have recently been linked to poor clinical outcome in various malignancies. The aim of this study was to evaluate the prognostic significance of the preoperative serum CRP level in patients with squamous cell carcinoma (SCC) of the penis. This retrospective analysis included 79 penile cancer patients with information about their serum CRP value prior to surgery who underwent either radical or partial penectomy at two German high-volume centers (Ulm University Medical Center and Hannover Medical School) between 1990 and 2010. They had a median (mean) follow-up of 23 (32) months. A significantly elevated CRP level (>15 vs. ≤ 15 mg/l) was found more often in patients with an advanced tumor stage (≥pT2) (38.9 vs. 11.6%, p=0.007) and in those with nodal disease at diagnosis (50.0 vs. 14.6%, p=0.007). However, high CRP levels were not associated with tumor differentiation (p=0.53). The Kaplan-Meier 5-year cancer-specific survival (CSS) rate was 38.9% for patients with preoperative CRP levels above 15 mg/l and 84.3% for those with lower levels (p=0.001). Applying multivariate analysis and focusing on the subgroup of patients without metastasis at the time of penile surgery, both advanced local tumor stage (≥pT2; HR 8.8, p=0.041) and an elevated CRP value (>15 mg/l; HR 3.3, p=0.043) were identified as independent predictors of poor clinical outcome in patients with penile cancer. A high preoperative serum CRP level was associated with poor survival in patients with penile cancer. If larger patient populations confirm its prognostic value, its routine use could enable better risk stratification and risk-adjusted follow-up of patients with SCC of the penis

EFFECT OF CRP ON SOME OF THE IN VITRO PHYSICOCHEMICAL PROPERTIES OF LDL

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Hashem Nayeri

2010-12-01

Full Text Available Abstract    BACKGROUND: Atherosclerosis is the most important underlying cause of cardiovascular diseases (CVD which recently has been classified as an inflammatory disorder. Accumulation of large amounts of oxidized LDL in the intima during local inflammation reaction led to increase several factors such as C -reactive protein (CRP. It has also been reported that CRP is able to bind with modified forms of LDL as well as oxidized LDL. These findings suggest possible positive or negative involvement of this protein in atherogenesis. The main objective of the present study was to assess the influence of CRP on LDL oxidation and the possible physical \\changes of LDL in the presence of CRP in vitro.    METHODS: In this study, the susceptibility of purified LDL to oxidation was assayed by monitoring of formation of conjugated dienes in different physiological concentrations of CRP (0 - 0.5 -2  µg/ml using a shimadzu spectrophotometer. Electrophoresis was used to determine the electrophoretic mobility of LDL in those conditions.    RESULTS: CRP significantly reduced the susceptibility of Cu++ -induced LDL oxidation through increasing the lag timeand there was positive relationship between these findings and CRP concentration (P < 0.05. CRP caused a significant reduction in the electrophotretic mobility of LDL compared to native LDL (n-LDL (P<0.05.     CONCLUSION: A considerable reduction was shown in LDL oxidation, in higher concentration of CRP, via an unknown mechanism. The electrophoretic mobility of LDL, in the oxidative condition, decreases in the presence of CRP compared to n-LDL, which can be indicative of the effect of this protein on the physical and chemical properties of LDL. It seems that, other pathway than LDL oxidation is responsible for the effect of CRP on the atherogenesis processes.      Keywords: Atherosclerosis, Creactive protein, Low-density lipoprotein, Inflammation.  

A comparison of osteoprotegerin with adiponectin and high-sensitivity C-reactive protein (hsCRP) as a marker for insulin resistance.

LENUS (Irish Health Repository)

O'Sullivan, Eoin P

2013-01-01

Insulin resistance (IR) is associated with low adiponectin and elevated high sensitivity C-reactive protein (hsCRP). Osteoprotegerin (OPG) has been shown to be elevated in type 2 diabetes, but whether it reflects underlying IR is unclear. We aimed to compare the ability of serum OPG with adiponectin and hsCRP to act as a marker for IR in individuals with normal and abnormal glucose tolerance.

Effects of haying on breeding birds in CRP grasslands

Science.gov (United States)

Igl, Lawrence D.; Johnson, Douglas H.

2016-01-01

The Conservation Reserve Program (CRP) is a voluntary program that is available to agricultural producers to help protect environmentally sensitive or highly erodible land. Management disturbances of CRP grasslands generally are not allowed unless authorized to provide relief to livestock producers during severe drought or a similar natural disaster (i.e., emergency haying and grazing) or to improve the quality and performance of the CRP cover (i.e., managed haying and grazing). Although CRP grasslands may not be hayed or grazed during the primary bird-nesting season, these disturbances may have short-term (1 yr after disturbance) and long-term (≥2 yr after disturbance) effects on grassland bird populations. We assessed the effects of haying on 20 grassland bird species in 483 CRP grasslands in 9 counties of 4 states in the northern Great Plains, USA between 1993 and 2008. We compared breeding bird densities (as determined by total-area counts) in idle and hayed fields to evaluate changes 1, 2, 3, and 4 years after haying. Haying of CRP grasslands had either positive or negative effects on grassland birds, depending on the species, the county, and the number of years after the initial disturbance. Some species (e.g., horned lark [Eremophila alpestris], bobolink [Dolichonyx oryzivorus]) responded positively after haying, and others (e.g., song sparrow [Melospiza melodia]) responded negatively. The responses of some species changed direction as the fields recovered from haying. For example, densities for common yellowthroat (Geothlypis trichas), sedge wren (Cistothorus platensis), and clay-colored sparrow (Spizella pallida) declined the first year after haying but increased in the subsequent 3 years. Ten species showed treatment × county interactions, indicating that the effects of haying varied geographically. This long-term evaluation on the effects of haying on breeding birds provides important information on the strength and direction of changes in

Performance of code 'FAIR' in IAEA CRP on FUMEX

International Nuclear Information System (INIS)

Swami Prasad, P.; Dutta, B.K.; Kushwaha, H.S.; Kakodkar, A.

1996-01-01

A modern fuel performance analysis code FAIR has been developed for analysing high burnup fuel pins of water/heavy water cooled reactors. The code employs finite element method for modelling thermo mechanical behaviour of fuel pins and mechanistic models for modelling various physical and chemical phenomena affecting the behaviour of nuclear reactor fuel pins. High burnup affects such as pellet thermal conductivity degradation, enhanced fission gas release and radial flux redistribution are incorporated in the code FAIR. The code FAIR is capable of performing statistical analysis of fuel pins using Monte Carlo technique. The code is implemented on BARC parallel processing system ANUPAM. The code has recently participated in an International Atomic Energy Agency (IAEA) coordinated research program (CRP) on fuel modelling at extended burnups (FUMEX). Nineteen agencies from different countries participated in this exercise. In this CRP, spread over a period of three years, a number of high burnup fuel pins irradiated at Halden reactor are analysed. The first phase of the CRP is a blind code comparison exercise, where the computed results are compared with experimental results. The second phase consists of modifications to the code based on the experimental results of first phase and statistical analysis of fuel pins. The performance of the code FAIR in this CRP has been very good. The present report highlights the main features of code FAIR and its performance in the IAEA CRP on FUMEX. 14 refs., 5 tabs., ills

Increased levels of the calcification marker matrix Gla Protein and the inflammatory markers YKL-40 and CRP in patients with type 2 diabetes and ischemic heart disease

DEFF Research Database (Denmark)

Thomsen, Stine B; Rathcke, Camilla N; Zerahn, Bo

2010-01-01

. In the present study levels of markers of calcification (MGP) and inflammation (YKL-40, hsCRP) were evaluated in patients with T2 D and/or ischemic heart disease (IHD). MATERIALS AND METHODS: The study population consisted of 1) patients with T2D (n = 45); 2) patients with IHD (n = 37); patients with both T2D......OBJECTIVE AND DESIGN: Low grade inflammation is of pathogenic importance in atherosclerosis and in the development of cardiovascular disease (CVD) and type 2 diabetes (T2D). Matrix GLA protein (MGP), an inhibitor of medial calcification of arteries, is increased in patients with atherosclerosis...... and IHD (n = 20) and 4) healthy controls (n = 20). Biochemical parameters were measured in venous blood samples. RESULTS: Levels of MGP, YKL-40 and hsCRP were increased in patients with IHD and/or T2D (p T2D and IHD had higher MGP levels (p

Relationship of the Adherence to a Mediterranean Diet and Its Main Components with CRP Levels in the Spanish Population.

Science.gov (United States)

Lahoz, Carlos; Castillo, Elisa; Mostaza, Jose M; de Dios, Olaya; Salinero-Fort, Miguel A; González-Alegre, Teresa; García-Iglesias, Francisca; Estirado, Eva; Laguna, Fernando; Sanchez, Vanesa; Sabín, Concesa; López, Silvia; Cornejo, Victor; de Burgos, Carmen; Garcés, Carmen

2018-03-20

Background: Adherence to a Mediterranean diet seems to be inversely associated with C-reactive protein (CRP) concentration. A 14-point Mediterranean Diet Adherence Screener (MEDAS) has been developed to assess dietary compliance. Objective: The aim of this study was to assess whether each of the MEDAS questions as well as their final score were associated with the levels of CRP in general Spanish population. Cross-sectional analysis of 1411 subjects (mean age 61 years, 43.0% males) randomly selected from the general population. CRP levels were determined by a commercial ELISA kit. Adherence to the Mediterranean diet was measured by the 14-point MEDAS. Results: There was an inverse correlation between adherence to the Mediterranean diet and the CRP concentration, even after adjusting by age, gender, hypertension, metabolic syndrome, body mass index, statin treatment and hypertension treatment ( p = 0.041). Subjects who consume ≥2 servings of vegetables per day ( p = 0.003), ≥3 pieces of fruit per day ( p = 0.003), ≥1 serving of butter, margarine, or cream per day ( p = 0.041) or ≥3 servings of fish/seafood per week ( p = 0.058) had significantly lower levels of CRP. Conclusions : Adherence to a Mediterranean-type diet measured by a simple questionnaire is associated with lower CRP concentration. However, this association seems to be particularly related to a higher consumption of vegetables, fruits, dairy products, and fish.

C-reactive protein (+1444C>T) polymorphism influences CRP response following a moderate inflammatory stimulus.

Science.gov (United States)

D'Aiuto, Francesco; Casas, Juan P; Shah, Tina; Humphries, Steve E; Hingorani, Aroon D; Tonetti, Maurizio S

2005-04-01

Elevations in C-reactive protein (CRP) concentration are associated with an increased risk of future coronary events in prospective studies and it has been suggested that CRP could be used to aid risk prediction. A +1444C>T polymorphism in the CRP gene has been associated with differences in CRP concentration. We investigated the effect of this polymorphism on the CRP response to periodontal therapy, an intermediate inflammatory stimulus. Clinical parameters, CRP, and interleukin-6 (IL-6) concentrations were evaluated in 55 consecutive patients suffering from periodontitis at baseline, 1, 7 and 30 days after an intensive course of periodontal treatment. In a multivariate analysis individuals homozygous for the +1444T allele showed higher CRP concentrations (day 1, 21.10+/-4.81 mg/L and day 7, 4.89+/-0.74 mg/L) compared with C-allele carriers (day 1, 12.37+/-1.61 mg/L and day 7, 3.08+/-2.00 mg/L). This effect was independent of conventional cardiovascular risk factors and inflammatory factors known to affect CRP concentrations. CRP genotype may need to be considered when CRP values are used in coronary risk prediction.

FNR demonstration experiments Part II: Subcadmium neutron flux measurements

International Nuclear Information System (INIS)

Wehe, D.K.; King, J.S.

1983-01-01

The FNR HEU-LEU Demonstration Experiments include a comprehensive set of experiments to identify and quantify significant operational differences between two nuclear fuel enrichments. One aspect of these measurements, the subcadmium flux profiling, is the subject of this paper. The flux profiling effort has been accomplished through foil and wire activations, and by rhodium self-powered neutron detector (SPND) mappings. Within the experimental limitations discussed, the program to measure subcadmium flux profiles, lead to the following conclusions: (1) Replacement of a single fresh HEU element by a fresh LEU element at the center of an equilibrium HEU core produces a local flux depression. The ratio of HEU to LEU local flux is 1.19 ± .036, which is, well within experimental uncertainty, equal to the inverse of the U-235 masses for the two elements. (2) Whole core replacement of a large 38 element equilibrium HEU core by a fresh or nearly unburned LEU core reduces the core flux and raises the flux in both D 2 O and H 2 O reflectors. The reduction in the central core region is 40% to 10.0% for the small fresh 29 element LEU core, and 16% to 18% for a 31 element LEU core 482) with low average burnup 2 O reflector fluxes relative to core fluxes as measured by SPND with a fixed value of sensitivity, are in gross disagreement with the same flux ratios measured by Fe and Rh wire activations. Space dependent refinements of S are calculated to give some improvement in the discrepancy but the major part of the correction remains to be resolved

Study of High Sensitive-CRP and Cardiac Marker Enzymes in Acute Coronary Syndrome

Directory of Open Access Journals (Sweden)

Srikrishna R,

2015-04-01

Full Text Available Background: Inflammation has been proposed as a contributor to different stages in the pathogenesis of Coronary Heart Disease (CHD. High sensitive C-Reactive Protein (hs-CRP, an acute-phase plasma protein synthesized by the liver, is the most extensively studied systemic marker of inflammation. Elevated hsCRP concentrations early in Acute Coronary Syndrome (ACS, prior to the tissue necrosis, may be a surrogate marker for cardiovascular co-morbidities. The cardiac marker enzymes Creatine Kinase myocardial bound (CK-MB, Aspartate Aminotransferase (AST and lactate dehydrogenase (LDH have been known to be increased in coronary artery diseases. Objective: The aim of the study was to measure hs-CRP levels and other cardiac marker enzymes in ACS patients and to compare the levels of hs-CRP with other cardiac marker enzymes between ST Elevation Myocardial Infarction (STEMI and Non-ST Elevation Myocardial Infarction (NSTEMI patients. Material and Methods: The study group consisted of 207 consecutive patients admitted to Sri Siddhartha Medical College Hospital within the first 6 hours from the onset of chest pain. Patients were diagnosed as Unstable Angina (UA, (n=84; STEMI (n=63 and NSTEMI (n=60. ACS patients were compared with 211 healthy age and sex matched controls. Hs-CRP, CK-MB, AST and LDH levels were measured by standard methods in both groups at baseline and forcases at 36-48 hours i.e. Peak levels. Results: ACS patients had significantly (p<0.05 higher levels of hs-CRP, CKMB, AST and LDH in comparison to controls at baseline. Hs-CRP, CK-MB, AST and LDH levels were significantly higher in STEMI patients compared to NSTEMI patients (p<0.05 at baseline. There was a significant difference regarding peak hs-CRP levels between the two groups, as STEMI patients had significantly higher peak hs-CRP levels compared to NSTEMI patients (p<0.05. Conclusion: STEMI patients have significantly higher peak hsCRP levels compared to NSTEMI patients. These data

Prognostic value of suPAR and hs-CRP on cardiovascular disease

DEFF Research Database (Denmark)

Diederichsen, Marie Zöga; Diederichsen, Søren Zöga; Mickley, Hans

2018-01-01

Background and aims: Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP...... have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score. Methods: A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events...

Design of cAMP-CRP-activated promoters in Escherichia coli

DEFF Research Database (Denmark)

Valentin-Hansen, P; Holst, B; Søgaard-Andersen, L

1991-01-01

We have studied the deoP2 promoter of Escherichia coli to define features that are required for optimal activation by the complex of adenosine 3',5' monophosphate (cAMP) and the cAMP receptor protein (CRP). Systematic mutagenesis of deoP2 shows that the distance between the CRP site and the -10...

C-Reactive Protein (CRP) and its Association with Periodontal Disease: A Brief Review.

Science.gov (United States)

Bansal, Tushika; Pandey, Anita; D, Deepa; Asthana, Ashish K

2014-07-01

Periodontal disease is a chronic infection of the gums characterised by a loss of attachment between the tooth and bone, and bone loss. C-reactive protein (CRP) elevation is a part of the acute phase response to acute and chronic inflammation. Many epidemiological studies have shown that serum CRP levels were elevated in patients with chronic periodontitis. CRP levels increase to hundreds of μg/ml within hours following infection. It out-performs erythrocyte sedimentation rate (ESR) in terms of responsiveness and specificity for inflammation. While CRP elevation is suggestive of inflammation or infection in the appropriate clinical context, it can also occur with obesity and renal dysfunction. Conversely, a lack of CRP elevation in inflammation may be seen with hepatic failure, as well as during flares of conditions such as systemic lupus erythematosus.

Vegetable and Fruit Intakes Are Associated with hs-CRP Levels in Pre-Pubertal Girls

Directory of Open Access Journals (Sweden)

Pilar Navarro

2017-03-01

Full Text Available The influence of diet on inflammation in children remains unclear. We aimed to analyze the influence of diet on high-sensitivity C-reactive protein (hs-CRP levels in a pre-pubertal population free of other influences that may affect hs-CRP levels. We determined hs-CRP levels in 571 six- to eight-year-old children using an hs-CRP ELISA kit. Information on food and nutrient intake was obtained through a food-frequency questionnaire. Overall dietary quality was assessed using the Healthy Eating Index (HEI. We found that girls in the highest tertile of hs-CRP levels had a higher intake of saturated fatty acid, and lower intakes of fiber and vitamin E and a lower HEI score when compared to those in tertiles 1 and 2. We also observed a significant decrease in fruit and vegetable intakes by hs-CRP tertile. Factor analysis showed that a dietary pattern that was loaded most strongly with vegetable, fruit, fiber and vitamin A and E intakes correlated negatively (−0.132, p < 0.05 with hs-CRP. No such association was found in boys. In conclusion, our data show that girls with a poorer quality diet show higher hs-CRP levels already at a pre-pubertal age.

Factors Affecting Conservation Practice Behavior of CRP Participants in Alabama

Science.gov (United States)

Okwudili Onianwa; Gerald Wheelock; Shannon Hendrix

1999-01-01

This study examines the factors that affect conservation practice choices of CRP farmers in Alabama. From over 9,000 contracts enrolled in the state between 1986 and 1995, 594 were randomly selected for the study. A multiple-regression analysis was employed to analyze the data. Results indicate that education, ratio ofcropland in CRP, farm size, gender, prior crop...

CRP on Demonstrating Performance of Spent Fuel and Related Storage Systems beyond the Long Term

International Nuclear Information System (INIS)

Bevilacqua, Arturo

2014-01-01

At the initial Coordinated Research Project (CRP) planning meeting held in August 2011, international experts in spent fuel performance confirmed the value of further coordination and development of international efforts to demonstrate the performance of spent fuel and related storage system components as durations extend. Furthermore, in recognition that the Extended Storage Collaboration Program (ESCP) managed by the Electric Power Research Institute (EPRI) in the USA, from now on ESCP, provided a broad context for the research and development work to be performed in the frame of this CRP, it was agreed that its objectives should target specific ESCP needs in order to make a relevant contribution. Accordingly, the experts examined on-going gap analyses - gaps between anticipated technical needs and existing technical data - for identify the specific research objectives. Additionally, during the planning meeting it was pointed out the need to coordinate and cooperate with the OECD/NEA counterparts involved in the organization of the International Workshop planned in autumn 2013 and with the on-going third phase of the CRP on Spent Fuel Performance Assessment and Research (SPAR-III). Given the importance to assess the performance of spent fuel and related important storage system components in order to confirm the viability of very long term storage for supporting the need to extend or renew licenses for storage facilities the CRP was approved by the IAEA in November 2011. While a full range of spent fuel types and storage conditions are deployed around the world, this CRP is focused on existing systems and, more specifically, water reactor fuel in dry storage with the overall research objective to support the technical basis for water reactor spent fuel management as dry storage durations extend. In March 2012 the group of international experts who participated at the initial CRP planning meeting in August 2011 evaluated and recommended for approval 9 research

Indonesia's experience with IAEA-CRP on radiation protection in diagnostic radiology

International Nuclear Information System (INIS)

Nasukha

2001-01-01

IAEA-CRP on Radiation Doses in Diagnostic Radiology and Methods for Dose Reduction has as participants some Asian and East European countries. Indonesia is one of participants that followed the IAEA program. This paper is not a discussion of CRP-results since it will be published as a TECDOC soon. But the work on evaluation of examination frequencies, film reject rate analysis, patient dose measurements, image quality before and after Quality Control (QC) and QC itself, gave some experiences to investigators to be explored and presented. Experiences could be in the form of problems, how to solve problems and some suggestions, starting from no QC up to complicated QC to be faced in conventional radiography to CT-scan and fluoroscopy units. These valuable experiences of Indonesia are proven exercise of IAEA-CRP as a good start for next CRP or national projects in diagnostic radiology. (author)

MetR and CRP bind to the Vibrio harveyi lux promoters and regulate luminescence.

Science.gov (United States)

Chatterjee, Jaidip; Miyamoto, Carol M; Zouzoulas, Athina; Lang, B Franz; Skouris, Nicolas; Meighen, Edward A

2002-10-01

The induction of luminescence in Vibrio harveyi at the later stages of growth is controlled by a quorum-sensing mechanism in addition to nutritional signals. However, the mechanism of transmission of these signals directly to the lux promoters is unknown and only one regulatory protein, LuxR, has been shown to bind directly to lux promoter DNA. In this report, we have cloned and sequenced two genes, crp and metR, coding for the nutritional regulators, CRP (cAMP receptor protein) and MetR (a LysR homologue), involved in catabolite repression and methionine biosynthesis respectively. The metR gene was cloned based on a general strategy to detect lux DNA-binding proteins expressed from a genomic library, whereas the crp gene was cloned based on its complementation of an Escherichia coli crp mutant. Both CRP and MetR were shown to bind to lux promoter DNA, with CRP being dependent on the presence of cAMP. Expression studies indicated that the two regulators had opposite effects on luminescence: CRP was an activator and MetR a repressor. Disruption of crp decreased luminescence by about 1,000-fold showing that CRP is a major activator of luminescence the same as LuxR, whereas disruption of MetR resulted in activation of luminescence over 10-fold, confirming its function as a repressor. Comparison of the levels of the autoinducers involved in quorum sensing excreted by V. harveyi, and the crp and metR mutants, showed that autoinducer production was not significantly different, thus indicating that the nutritional signals do not affect luminescence by changing the levels of the signals required for quorum sensing. Indeed, the large effects of these nutritional sensors show that luminescence is controlled by multiple signals related to the environment and the cell density which must be integrated at the molecular level to control expression at the lux promoters.

Why cellular communication during plant reproduction is particularly mediated by CRP signalling.

Science.gov (United States)

Bircheneder, Susanne; Dresselhaus, Thomas

2016-08-01

Secreted cysteine-rich peptides (CRPs) represent one of the main classes of signalling peptides in plants. Whereas post-translationally modified small non-CRP peptides (psNCRPs) are mostly involved in signalling events during vegetative development and interactions with the environment, CRPs are overrepresented in reproductive processes including pollen germination and growth, self-incompatibility, gamete activation and fusion as well as seed development. In this opinion paper we compare the involvement of both types of peptides in vegetative and reproductive phases of the plant lifecycle. Besides their conserved cysteine pattern defining structural features, CRPs exhibit hypervariable primary sequences and a rapid evolution rate. As a result, CRPs represent a pool of highly polymorphic signalling peptides involved in species-specific functions during reproduction and thus likely represent key players to trigger speciation in plants by supporting reproductive isolation. In contrast, precursers of psNCRPs are proteolytically processed into small functional domains with high sequence conservation and act in more general processes. We discuss parallels in downstream processes of CRP signalling in both reproduction and defence against pathogenic fungi and alien pollen tubes, with special emphasis on the role of ROS and ion channels. In conclusion we suggest that CRP signalling during reproduction in plants has evolved from ancient defence mechanisms. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A mutant crp allele that differentially activates the operons of the fuc regulon in Escherichia coli.

Science.gov (United States)

Zhu, Y; Lin, E C

1988-05-01

L-Fucose is used by Escherichia coli through an inducible pathway mediated by a fucP-encoded permease, a fucI-encoded isomerase, a fucK-encoded kinase, and a fucA-encoded aldolase. The adolase catalyzes the formation of dihydroxyacetone phosphate and L-lactaldehyde. Anaerobically, lactaldehyde is converted by a fucO-encoded oxidoreductase to L-1,2-propanediol, which is excreted. The fuc genes belong to a regulon comprising four linked operons: fucO, fucA, fucPIK, and fucR. The positive regulator encoded by fucR responds to fuculose 1-phosphate as the effector. Mutants serially selected for aerobic growth on propanediol became constitutive in fucO and fucA [fucO(Con) fucA(Con)], but noninducible in fucPIK [fucPIK(Non)]. An external suppressor mutation that restored growth on fucose caused constitutive expression of fucPIK. Results from this study indicate that this suppressor mutation occurred in crp, which encodes the cyclic AMP-binding (or receptor) protein. When the suppressor allele (crp-201) was transduced into wild-type strains, the recipient became fucose negative and fucose sensitive (with glycerol as the carbon and energy source) because of impaired expression of fucA. The fucPIK operon became hyperinducible. The growth rate on maltose was significantly reduced, but growth on L-rhamnose, D-galactose, L-arabinose, glycerol, or glycerol 3-phosphate was close to normal. Lysogenization of fuc+ crp-201 cells by a lambda bacteriophage bearing crp+ restored normal growth ability on fucose. In contrast, lysogenization of [fucO(Con)fucA(Con)fucPIK(Non)crp-201] cells by the same phage retarded their growth on fucose.

Increased hsCRP is associated with higher risk of aortic valve replacement in patients with aortic stenosis

DEFF Research Database (Denmark)

Blyme, Adam; Nielsen, Olav W.; Asferg, Camilla

2016-01-01

Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP0) and after 1 year (hsCRP1) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from...... the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9–4.9] to 1.8 [0.8–5.4] mg/l, p CRP1...... predicted later AVR (HR = 1.17, p CRP0 (HR = 0.96, p = 0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP0 and an increase during the first year (AVRhighCRP0CRP1inc=47.3% versus AVRhighCRP0CRP1dec=27.5%, p

Land use type significantly affects microbial gene transcription in soil.

Science.gov (United States)

Nacke, Heiko; Fischer, Christiane; Thürmer, Andrea; Meinicke, Peter; Daniel, Rolf

2014-05-01

Soil microorganisms play an essential role in sustaining biogeochemical processes and cycling of nutrients across different land use types. To gain insights into microbial gene transcription in forest and grassland soil, we isolated mRNA from 32 sampling sites. After sequencing of generated complementary DNA (cDNA), a total of 5,824,229 sequences could be further analyzed. We were able to assign nonribosomal cDNA sequences to all three domains of life. A dominance of bacterial sequences, which were affiliated to 25 different phyla, was found. Bacterial groups capable of aromatic compound degradation such as Phenylobacterium and Burkholderia were detected in significantly higher relative abundance in forest soil than in grassland soil. Accordingly, KEGG pathway categories related to degradation of aromatic ring-containing molecules (e.g., benzoate degradation) were identified in high abundance within forest soil-derived metatranscriptomic datasets. The impact of land use type forest on community composition and activity is evidently to a high degree caused by the presence of wood breakdown products. Correspondingly, bacterial groups known to be involved in lignin degradation and containing ligninolytic genes such as Burkholderia, Bradyrhizobium, and Azospirillum exhibited increased transcriptional activity in forest soil. Higher solar radiation in grassland presumably induced increased transcription of photosynthesis-related genes within this land use type. This is in accordance with high abundance of photosynthetic organisms and plant-infecting viruses in grassland.

ChIP-exo interrogation of Crp, DNA, and RNAP holoenzyme interactions

DEFF Research Database (Denmark)

Latif, Haythem; Federowicz, Stephen; Ebrahim, Ali

2018-01-01

Numerous in vitro studies have yielded a refined picture of the structural and molecular associations between Cyclic-AMP receptor protein (Crp), the DNA motif, and RNA polymerase (RNAP) holoenzyme. In this study, high-resolution ChIP-exonuclease (ChIP-exo) was applied to study Crp binding in vivo...

Anti-bacterial activity of Achatina CRP and its mechanism of action.

Science.gov (United States)

Mukherjee, Sandip; Barman, Soma; Mandal, Narayan Chandra; Bhattacharya, Shelley

2014-07-01

The physiological role of C-reactive protein (CRP), the classical acute-phase protein, is not well documented, despite many reports on biological effects of CRP in vitro and in model systems in vivo. It has been suggested that CRP protects mice against lethal toxicity of bacterial infections by implementing immunological responses. In Achatina fulica CRP is a constitutive multifunctional protein in haemolymph and considered responsible for their survival in the environment for millions of years. The efficacy of Achatina CRP (ACRP) was tested against both Salmonella typhimurium and Bacillus subtilis infections in mice where endogenous CRP level is negligible even after inflammatory stimulus. Further, growth curves of the bacteria revealed that ACRP (50 microg/mL) is bacteriostatic against gram negative salmonellae and bactericidal against gram positive bacilli. ACRP induced energy crises in bacterial cells, inhibited key carbohydrate metabolic enzymes such as phosphofructokinase in glycolysis, isocitrate dehydrogenase in TCA cycle, isocitrate lyase in glyoxylate cycle and fructose-1,6-bisphosphatase in gluconeogenesis. ACRP disturbed the homeostasis of cellular redox potential as well as reduced glutathione status, which is accompanied by an enhanced rate of lipid peroxidation. Annexin V-Cy3/CFDA dual staining clearly showed ACRP induced apoptosis-like death in bacterial cell population. Moreover, immunoblot analyses also indicated apoptosis-like death in ACRP treated bacterial cells, where activation of poly (ADP-ribose) polymerase-1 (PARP) and caspase-3 was noteworthy. It is concluded that metabolic impairment by ACRP in bacterial cells is primarily due to generation of reactive oxygen species and ACRP induced anti-bacterial effect is mediated by metabolic impairment leading to apoptosis-like death in bacterial cells.

Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial.

Science.gov (United States)

Ebrahimpour Koujan, Soraiya; Gargari, Bahram Pourghassem; Mobasseri, Majid; Valizadeh, Hadi; Asghari-Jafarabadi, Mohammad

2015-02-15

Diabetes is a serious metabolic disorder and oxidative stress and inflammation contribute to its pathogenesis and complications. Since Silybum marianum (L.) Gaertn. (silymarin) extract is an antioxidant with anti-inflammatory properties, this randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on oxidative stress indices and hs-CRP in type 2 diabetes mellitus patients. For the present paralleled, randomized, triple-blinded, placebo-controlled clinical trial, 40 type 2 diabetes patients aged 25-50 yr old and on stable medication were recruited from the Iranian Diabetes Society and endocrinology clinics in East Azarbayjan (Tabriz, Iran) and randomly assigned into two groups. Patients in the silymarin treatment group received 140 mg, thrice daily of dried extracts of Silybum marianum (n = 20) and those in the placebo group (n = 20) received identical placebos for 45 days. Data pertaining to height, weight, waist circumference and BMI, as well as food consumption, were collected at base line and at the conclusion of the study. Fasting blood samples were obtained and antioxidant indices and hs-CRP were assessed at baseline, as well as at the end of the trial. All 40 patients completed the study and did not report any adverse effects or symptoms with the silymarin supplementation. Silymarin supplementation significantly increased superoxide dismutase (SOD), glutathione peroxidase (GPX) activity and total antioxidant capacity (TAC) compared to patients taking the placebo, by 12.85%, 30.32% and 8.43%, respectively (p concentration significantly decreased by 12.01% (p antioxidant indices (SOD, GPX and TAC) and decrease hs-CRP levels in T2DM patients. Copyright © 2015. Published by Elsevier GmbH.

High-affinity RNA aptamers to C-reactive protein (CRP): newly developed pre-elution methods for aptamer selection

International Nuclear Information System (INIS)

Orito, N; Umekage, S; Sakai, E; Tanaka, T; Kikuchi, Y; Sato, K; Kawauchi, S; Tanaka, H

2012-01-01

We have developed a modified SELEX (systematic evolution of ligands by exponential enrichment) method to obtain RNA aptamers with high affinity to C-reactive protein (CRP). CRP is a clinical biomarker present in plasma, the level of which increases in response to infections and noninfectious inflammation. The CRP level is also an important prognostic indicator in patients with several syndromes. At present, CRP content in blood is measured immunochemically using antibodies. To develop a more sensitive method using RNA aptamers, we have attempted to obtain high-affinity RNA aptamers to CRP. We succeeded in obtaining an RNA aptamer with high affinity to CRP using a CRP-immobilized Sepharose column and pre-elution procedure. Pre-elution is a method that removes the weak binding portion from a selected RNA population by washing for a short time with buffer containing CRP. By surface plasmon-resonance (SPR) analysis, the affinity constant of this aptamer for CRP was calculated to be K D = 2.25x10 -9 (M). The secondary structure, contact sites with CRP protein, and application of this aptamer will be described.

aldB, an RpoS-dependent gene in Escherichia coli encoding an aldehyde dehydrogenase that is repressed by Fis and activated by Crp.

Science.gov (United States)

Xu, J; Johnson, R C

1995-06-01

Escherichia coli aldB was identified as a gene that is negatively regulated by Fis but positively regulated by RpoS. The complete DNA sequence determined in this study indicates that aldB encodes a 56.3-kDa protein which shares a high degree of homology with an acetaldehyde dehydrogenase encoded by acoD of Alcaligenes eutrophus and an aldehyde dehydrogenase encoded by aldA of Vibrio cholerae and significant homology with a group of other aldehyde dehydrogenases from prokaryotes and eukaryotes. Expression of aldB is maximally induced during the transition from exponential phase to stationary phase. Its message levels are elevated three- to fourfold by a fis mutation and abolished by an rpoS mutation. In addition, the expression of an aldB-lacZ fusion was decreased about 20-fold in the absence of crp. DNase I footprinting analysis showed that five Fis binding sites and one Crp binding site are located within the aldB promoter region, suggesting that Fis and Crp are acting directly to control aldB transcription. AldB expression is induced by ethanol, but in contrast to that of most of the RpoS-dependent genes, the expression of aldB is not altered by an increase in medium osmolarity.

Diagnostic value of CRP and Lp(a) in coronary heart disease.

Science.gov (United States)

Erbağci, Ayşe Binnur; Tarakçioğlu, Mehmet; Aksoy, Mehmet; Kocabaş, Ramazan; Nacak, Muradiye; Aynacioğlu, A Sükrü; Sivrikoz, Cumhur

2002-06-01

Increased lipoprotein (a) [Lp(a)] concentration was reported to be an independent risk factor for coronary heart disease (CHD). Recent epidemiological studies affirmed the value of C-reactive protein (CRP) as the strongest, univariate predictor of the cardiovascular events. We decided to establish cut-off levels providing maximum diagnostic efficiency for CHD. In this study we measured CRP and Lp(a) concentrations in patients with angiographically demonstrated CHD (group A, n: 120), patients without any angiographically demonstrable lesion (group B, n: 62) and a group of healthy subjects (group C, n: 41). Data were evaluated correcting for lipid and lipoprotein concentrations, diabetes mellitus, hypertension, smoking, age, and body mass index in men and women. ROC curve based cut-off values (comparing group A versus groups B and C) and associated diagnostic performances of the assays were evaluated. Significant increases were noted in serum CRP concentrations in men and women, in groups A vs. B,A vs. C, B vs. C. Lp(a) concentrations were not different among groups in men but were higher in group A vs. B and C in women. Optimal cut-off levels for CRP in women and men were found as 2.1 and 3.0 mg/l with the diagnostic values of 0.792 and 0.770, respectively. For Lp(a) optimal cut-off levels were found as 22.6 and 9.8 mg/dl with the diagnostic values of 0.612 and 0.596 in women and men, respectively. The CRP level is quite efficient for separation of patients from controls. Therefore keeping in mind the lack of specificity, the CRP level may be a useful tool in the diagnosis of coronary heart disease. However, the Lp(a) level is not efficient enough to support the use of Lp(a) measurement for management of coronary heart disease.

CRP and suPAR are differently related to anthropometry and subclinical organ damage

DEFF Research Database (Denmark)

Lyngbæk, Stig; Sehestedt, Thomas; Marott, Jacob L

2013-01-01

BACKGROUND: Low-grade inflammation is a marker for cardiovascular disease (CVD). The inflammatory biomarkers C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR) independently predict CVD. We tested the hypothesis that these biomarkers reflect different aspects...... of the inflammation associated with CVD. METHODS: We studied 2273 subjects without CVD. Log-transformed CRP and suPAR were included in general linear and logistic regression models to compare associations with measures of anthropometry and subclinical organ damage (SOD). Owing to interactions on body mass index (BMI......) (P3: 1.31 (1.16-1.47), whereas log-CRP was not (1.00 (0.89-1.11))). CONCLUSIONS: CRP is positively associated with anthropometric measures, whereas suPAR is linked to endothelial dysfunction and atherosclerosis....

Mammalian transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes and are predicted to act as transcriptional activator hubs.

Science.gov (United States)

Joshi, Anagha

2014-12-30

Transcriptional hotspots are defined as genomic regions bound by multiple factors. They have been identified recently as cell type specific enhancers regulating developmentally essential genes in many species such as worm, fly and humans. The in-depth analysis of hotspots across multiple cell types in same species still remains to be explored and can bring new biological insights. We therefore collected 108 transcription-related factor (TF) ChIP sequencing data sets in ten murine cell types and classified the peaks in each cell type in three groups according to binding occupancy as singletons (low-occupancy), combinatorials (mid-occupancy) and hotspots (high-occupancy). The peaks in the three groups clustered largely according to the occupancy, suggesting priming of genomic loci for mid occupancy irrespective of cell type. We then characterized hotspots for diverse structural functional properties. The genes neighbouring hotspots had a small overlap with hotspot genes in other cell types and were highly enriched for cell type specific function. Hotspots were enriched for sequence motifs of key TFs in that cell type and more than 90% of hotspots were occupied by pioneering factors. Though we did not find any sequence signature in the three groups, the H3K4me1 binding profile had bimodal peaks at hotspots, distinguishing hotspots from mono-modal H3K4me1 singletons. In ES cells, differentially expressed genes after perturbation of activators were enriched for hotspot genes suggesting hotspots primarily act as transcriptional activator hubs. Finally, we proposed that ES hotspots might be under control of SetDB1 and not DNMT for silencing. Transcriptional hotspots are enriched for tissue specific enhancers near cell type specific highly expressed genes. In ES cells, they are predicted to act as transcriptional activator hubs and might be under SetDB1 control for silencing.

Biofunctionalized gold nanoparticle-conducting polymer nanocomposite based bioelectrode for CRP detection.

Science.gov (United States)

Mishra, Sujeet K; Sharma, Vikash; Kumar, Devendra; Rajesh

2014-10-01

An electrochemical impedance immunosensing method for the detection and quantification of C-reactive protein (αCRP) in phosphate buffered saline (PBS) is demonstrated. The protein antibody, Ab-αCRP, has been covalently immobilized on a platform comprising of electrochemically deposited 3-mercaptopropionic acid-capped gold nanoparticles Au(MPA)-polypyrrole (PPy) nanocomposite film of controlled thickness onto an indium tin oxide-coated glass plate. The free carboxyl groups present on the nanocomposite film have been used to site-specifically immobilize the Ab-αCRP biomolecules through a stable acyl amino ester intermediate generated by N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide hydrochloride and N-hydroxysuccinimide. The nanocomposite film was characterized by atomic force microscopy, high-resolution transmission electron microscopy, Fourier transform infrared spectroscopy, and electrochemical techniques. The bioelectrode was electrochemically analyzed using modified Randles circuit in terms of constant phase element (CPE), electron transfer resistance (R et), and Warburg impedance (Z w). The value of n, a CPE exponent used as a gauge of heterogeneity, for the Au-PPy nanocomposite film was found to be 0.56 which is indicative of a rather rough morphology and porous structure. A linear relationship between the increased ∆R et values and the logarithmic value of protein antigen, Ag-αCRP, concentrations was found in the range of 10 ng to 10 μg mL(-1) with a R et sensitivity of 46.27 Ω cm(2)/decade of [Ag-αCRP] in PBS (pH 7.4).

Ultra-Sensitive C-Reactive Protein (US-CRP) in Patients With Periodontal Disease and Risk of Acute Myocardial Infarction.

Science.gov (United States)

Uriza, Catalina Latorre; Arregoces, Francina Escobar; Porras, Juliana Velosa; Camargo, Maria Beatriz Ferro; Morales, Alvaro Ruiz

2011-02-01

The purpose of this study was to determine if the US-CRP values associated with periodontal disease are risk markers for Acute Myocardial Infarction (AMI) and to determine if the US-CRP levels associated with recent AMI are higher in patients with Periodontal disease. In order to meet the goal of the study, a case control study design was conducted. The analysis sample consisted of 401 adults (30 - 75 years old), living in Bogota D.C., Colombia, from the Hospital Universitario San Ignacio, the Faculty of Dentistry at the Pontificia Universidad Javeriana, and the Fundacion Cardio Infantil. Patients with current infections, antibiotic use in the last 3 months, periodontal treatment at least six months before the baseline of this study, mouth ulcerations caused by any type of prosthesis, candidiasis, stomatitis, or less than 7 teeth in mouth were excluded. Periodontal examination for the case group and the control group was conducted by three previously calibrated examiners. Periodontal disease was diagnosed by the presence of bleeding on probing and attachment loss. The Chronic Periodontitis diagnosis was confirmed with these clinical signs, according to the 1999 Armitage classification. The assessment of the US-CRP was performed using the IMMULITE method containing one monoclonal and one polyclonal anti-CRP antibody. This method provides a measurement range of 0.1 - 500 mg/L. Statistical analysis of variables was performed with OR and confidence intervals. A multivariate analysis was performed to determine the association between the US-CRP increase, periodontal disease and acute myocardial infarction, adjusting for smoking and other confounding factors identified in the analysis. The study population was constituted by 401 patients, 56.1% (225) males, with a mean age of 52.6. When groups were compared it was observed that, in those patients with AMI and chronic severe or moderate periodontitis, 24.2% had HDL-C values lower than 40 mg/dl, 78.8% had LDL-C values

The ratio of CRP to prealbumin levels predict mortality in patients with hospital-acquired acute kidney injury

Directory of Open Access Journals (Sweden)

Hao Chuanming

2011-06-01

Full Text Available Abstract Background Animal and human studies suggest that inflammation and malnutrition are common in acute kidney injury (AKI patients. However, only a few studies reported CRP, a marker of inflammation, albumin, prealbumin and cholesterol, markers of nutritional status were associated with the prognosis of AKI patients. No study examined whether the combination of inflammatory and nutritional markers could predict the mortality of AKI patients. Methods 155 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney criteria. C-reactive protein (CRP, and the nutritional markers (albumin, prealbumin and cholesterol measured at nephrology consultation were analyzed in relation to all cause mortality of these patients. In addition, CRP and prealbumin were also measured in healthy controls (n = 45, maintenance hemodialysis (n = 70 and peritoneal dialysis patients (n = 50 and then compared with AKI patients. Results Compared with healthy controls and end-stage renal disease patients on maintenance hemodialysis or peritoneal dialysis, patients with AKI had significantly higher levels of CRP/prealbumin (p 28 days. Similarly, the combined factors including the ratio of CRP to albumin (CRP/albumin, CRP/prealbumin and CRP/cholesterol were also significantly higher in the former group (p p = 0.027 while the others (CRP, albumin, prealbumin, cholesterol, CRP/albumin and CRP/cholesterol became non-significantly associated. The hazard ratio was 1.00 (reference, 1.85, 2.25 and 3.89 for CRP/prealbumin increasing according to quartiles (p = 0.01 for the trend. Conclusions Inflammation and malnutrition were common in patients with AKI. Higher level of the ratio of CRP to prealbumin was associated with mortality of AKI patients independent of the severity of illness and it may be a valuable addition to SOFA score to independent of the severity of illness and it may be a

Evaluation of Usefulness of hs-CRP and Ferritin Assays in Patients with Nasal Polyps

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Robert Partyka

2014-01-01

Full Text Available Background. Chronic nature of the nasal polyps, tendency to recurrence, and lack of satisfying treatment need the diagnostic’s parameters which show early inflammatory state as ferritin and hs-CRP. The Aim of Study. Assessment of hs-CRP and ferritin blood levels in nasal polyps patients in evaluation of treatment efficacy. Methods. All 38 patients were divided into 2 groups. Group I included 19 patients with anti-inflammatory therapy 2 weeks after surgery. Group II included 19 patients without anti-inflammatory therapy 2 weeks after surgery. The levels of hs-CRP and ferritin have been assessed before and 2 and 6 weeks after surgical treatment. Results. Research showed statistically significant difference of ferritin’s concentration between examined groups 6 weeks after surgery (P<0.05 and statistically significant difference of hs-CRP concentration 2 and 6 weeks after surgery (P<0.05. Conclusion. (1 The analysis of serum ferritin and hs-CRP concentrations can be useful in early postoperative detection of inflammatory state in patients with nasal polyps and for the effectiveness of therapy. (2 Lack of correlation between mean ferritin and hs-CRP serum levels, at each diagnostic and monitoring stage, shows that they are independent and cannot be determined interchangeably.

Analysis of OLAB, BNP and CRP levels in the plasma of patients with cardiovascular disease

International Nuclear Information System (INIS)

Du Tongxin; Wang Zizheng; Wang Shukui; Fu Lei; Luo Jun

2004-01-01

To explore the mechanism of coronary heart disease and the effect of therapy on unstable angina pectoris (UAP) OLAB, brain natriuretic peptide (BNP) and supersensitive C reaction protein(CRP) levels in the plasma of patients with coronary heart disease were detected. The OLAB, BNP and CRP levels and their correlations in the plasma of 124 patients with coronary heart disease and 30 controls were determined by chemiluminescence and ELISA technique, respectively. The OLAB, BNP and CRP levels of 48 UAP patients after PTCA were also analyzed. The BNP and CRP levels of patients with coronary heart disease, especially acute myocardial infarction (AMI) and UAP patients to stable angina pectoris (SAP) patients were higher than those of controls (P<0.01). The OLAB levels in AMI patients was higher than UAP, SAP and controls (P<0.05). There was a significant difference of OLAB, BNP and CRP levels in UAP patients before and after PTCA therapy (P<0.05). OLAB, BNP and CRP, which is involved in the developing procedure of coronary heart disease, may be used to predict the long-term cardiac function recover. OLAB, BNP and CRP levels in UAP patients were decreased significantly after PTCA and may also be considered as the therapy effect observing markers. OLAB takes part in the whole procedure of coronary atherosclerosis and the occurrence and ending of AMI. (authors)

Effects of aerobic and anaerobic training programs together with omega-3 supplement on interleukin-17 and CRP plasma levels in male mice.

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Alizadeh, Hamid; Daryanoosh, Farhad; Moatari, Maryam; Hoseinzadeh, Khadijeh

2015-01-01

Herein, we studied the effects of two different exercise protocols on IL-17 and CRP plasma levels along with the anti-inflammatory effects of fish oil. The purpose of the present study was to investigate the effect of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) consumption along with two different types of physical activities on IL-17 and CRP plasma levels in trained male mice. A total of 130 adult male mice of Syrian race with the age of 2 months and the weight of 35±1 grams were selected. At the beginning, 10 mice were killed in order to determine the amounts of pre-test variables. The rest of the mice were randomly divided into 6 groups including control group (n=20), supplement (n=20), aerobic exercise (n=20), anaerobic exercise (n=20), supplementaerobic exercise (n=20), and supplement-anaerobic exercise (n=20). Blood samples were withdrawn from the tail under intraperitoneal ketamine and xylasine anaesthesia. The anaerobic training program included 8 weeks of running on treadmill, 3 sessions per week; the aerobic training program included 8 weeks of running on treadmill, 5 sessions per week. At the end of the training program, the blood sample from each group was taken in order to measure the CRP and IL-17 levels. The analysis of variance (ANOVA) was used to determine the differences among the groups. The results showed that there was a significant difference in IL-17 and CRP plasma levels between the groups after 8 weeks (Ptraining programs, both IL-17 and CRP plasma levels increased, although these observed increases were not same for two measured variables. The results might also show that the effect of the supplement depends on the type of training.

Regulation of pelD and pelE, encoding major alkaline pectate lyases in Erwinia chrysanthemi: involvement of the main transcriptional factors.

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Rouanet, C; Nomura, K; Tsuyumu, S; Nasser, W

1999-10-01

The main virulence factors of the phytopathogenic bacterium Erwinia chrysanthemi are pectinases which attack pectin, the major constituent of the plant cell wall. Of these enzymes, the alkaline isoenzyme named PelD in strain 3937 and PelE in strain EC16 has been described as being particularly important, based on virulence studies of plants. Expression of the pelD and pelE genes is tightly modulated by various regulators, including the KdgR repressor and the cyclic AMP-cyclic AMP receptor protein (CRP) activator complex. The use of a lacZ reporter gene allowed us to quantify the repression of E. chrysanthemi 3937 pelD expression exerted by PecS, another repressor of pectinase synthesis. In vitro DNA-protein interaction experiments, centered on the pelD and pelE wild-type or pelE mutated promoter regions, allowed us to define precisely the sequences involved in the binding of these three regulators and of RNA polymerase (RNAP). These studies revealed an unusual binding of the KdgR repressor and suggested the presence of a UP (upstream) element in the pelD and pelE genes. Investigation of the simultaneous binding of CRP, KdgR, PecS, and the RNAP to the regulatory region of the pelD and pelE genes showed that (i) CRP and RNAP bind cooperatively, (ii) PecS partially inhibits binding of the CRP activator and of the CRP-RNAP complex, and (iii) KdgR stabilizes the binding of PecS and prevents transcriptional initiation by RNAP. Taken together, our data suggest that PecS attenuates pelD and pelE expression rather than acting as a true repressor like KdgR. Overall, control of the pelD and pelE genes of E. chrysanthemi appears to be both complex and novel.

Elevated CRP levels during first trimester of pregnancy and subsequent preeclampsia: a prospective study

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Beigi A

2008-06-01

Full Text Available Background: Whatever its etiology, the inflammatory reactions of preeclampsia lead to the activation of endothelium and result in vascular damage. CRP is considered a sensitive index of systemic inflammation, so it is used as predictive factor for disease. This study was carried out to test the screening and predictive abilities of the CRP test in order to detect and diagnose pregnant women prone to preeclampsia prior to the onset of symptoms.Methods: In this prospective cohort study, conducted in Arash Hospital between 2005 and 2006, we determined the CRP levels of 201 pregnant women at 10-16 weeks of pregnancy. Based on exclusion criteria and illness, 31 patients were excluded and 170 patients were followed until the end of their pregnancies.Results: In this study, the mean serum CRP values of those who had preeclamptic and those who had normal pregnancies were compared and the statistical differences were significant: 6.18 mg/L for preeclamptic patients compared with 4.12 mg/L for normal patients (p=0.003. Using a chi-square test, we found that patients whose CRP level was ≥4 were six times more likely to have preeclampsia than those with CRP levels <4 (k=9.4; p=0.002; OR=6.15; 95% CI=0.69-22.28.Conclusion: This study confirms the results of previous reports indicating a significant relationship between rising serum CRP in the first trimester of pregnancy and preeclampsia at third trimester. More studies consisting of other inflammation factors are necessary to find an acceptable and reasonable screening test to diagnose pregnant women who are prone to preeclampsia.

Comparative genomics of CytR, an unusual member of the LacI family of transcription factors.

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Natalia V Sernova

Full Text Available CytR is a transcription regulator from the LacI family, present in some gamma-proteobacteria including Escherichia coli and known not only for its cellular role, control of transport and utilization of nucleosides, but for a number of unusual structural properties. The present study addressed three related problems: structure of CytR-binding sites and motifs, their evolutionary conservation, and identification of new members of the CytR regulon. While the majority of CytR-binding sites are imperfect inverted repeats situated between binding sites for another transcription factor, CRP, other architectures were observed, in particular, direct repeats. While the similarity between sites for different genes in one genome is rather low, and hence the consensus motif is weak, there is high conservation of orthologous sites in different genomes (mainly in the Enterobacteriales arguing for the presence of specific CytR-DNA contacts. On larger evolutionary distances candidate CytR sites may migrate but the approximate distance between flanking CRP sites tends to be conserved, which demonstrates that the overall structure of the CRP-CytR-DNA complex is gene-specific. The analysis yielded candidate CytR-binding sites for orthologs of known regulon members in less studied genomes of the Enterobacteriales and Vibrionales and identified a new candidate member of the CytR regulon, encoding a transporter named NupT (YcdZ.

7 CFR 1410.22 - CRP conservation plan.

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2010-01-01

... productive capability of the soil, improve water quality, protect wildlife or wetlands, protect a public well... plans and revisions of such plans shall be subject to the approval of CCC. (f) Mid-cover management... 7 Agriculture 10 2010-01-01 2010-01-01 false CRP conservation plan. 1410.22 Section 1410.22...

Clinical trial evaluating the effectiveness of biocompound IMMUNEPOTENT CRP in the third-molar extraction

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Moises A. Franco-Molina

2017-01-01

Full Text Available A controlled, parallel, randomized and comparative trial was carried out to evaluate the anti-inflammatory efficacy of IMMUNEPOTENT CRP versus ibuprofen in patients after third-molar surgery over seven days. The anti-inflammatory efficacy of IMMUNEPOTENT CRP was evaluated using the method of Amin and Laskin, and the analysis of cytokine production (IL-2, IL-4, IL-6, IL-10, TNF-α, INF-γ in saliva was done by flow cytometry. The swelling process after surgery was significant (p < 0.05 and the treatments with IMMUNEPOTENT CRP or ibuprofen controlled this process properly; no difference between the groups was found (p < 0.05. Both treatments were shown to modulate the cytokine production. These results demonstrate the anti-inflammatory activity of the natural compound IMMUNEPOTENT CRP and suggest it could be used in clinical dental practice.

High-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of polycystic ovary syndrome in Indian adolescent women with polycystic ovary syndrome (PCOS).

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Ganie, Mohd Ashraf; Hassan, Saqib; Nisar, Sobia; Shamas, Nasir; Rashid, Aafia; Ahmed, Ishfaq; Douhat, Syed; Mudassar, Syed; Jan, Vicar M; Rashid, Fouzia

2014-11-01

C-reactive protein (CRP) is a risk marker for type 2 diabetes mellitus and cardiovascular diseases. In polycystic ovary syndrome (PCOS), limited data are available on high-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of PCOS especially in Indian women. The objective was to determine serum hs-CRP concentration in adolescent women with and without PCOS and to assess possible correlations of serum hs-CRP levels with components of PCOS in Indian women. One hundred and sixty women with PCOS and sixty non-PCOS women having normal menstrual cycles were included. Clinical assessment included anthropometry, Ferriman-Gallwey (FG) score and blood pressure (BP) measurement. Laboratory evaluation included estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, hs-CRP, lipid profile, and insulin, and glucose after 2-h oral glucose tolerance test. Homeostasis Model Assessment Insulin resistance index (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) and glucose intolerance was calculated. FG score, LH, FSH, total Testosterone, HOMA-IR and QUICKI were significantly different among women with or without PCOS (p women having PCOS, there was no significant difference between the groups (p > 0.05). A significant and positive correlation was found between hs-CRP and body mass index (BMI) (r = 0.308, p Indian adolescent women suggest that hs-CRP levels may not per se be associated with PCOS, rather can be related to fat mass in this subset of subjects.

High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men.

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Jieun Lee

Full Text Available We performed a follow-up study to address whether high sensitivity C-reactive protein (hs-CRP levels within the normal range can predict the development of non-alcoholic fatty liver disease (NAFLD in healthy male subjects. Among15347 male workers between 30 and 59 years old who received annual health check-ups in 2002, a NAFLD-free cohort of 4,138 was followed through December 2009. Alcohol consumption was assessed with a questionnaire. At each visit, abdominal ultrasonography was performed to identify fatty liver disease. The COX proportional hazard model was used to evaluate the relationship between hs-CRP and incident NAFLD. During the follow-up period, 28.8% (1191 of 4138 of participants developed NAFLD. The hazard ratios of NAFLD were increased by hs-CRP categories within the normal range in the non-adjusted model and age-adjusted model. After adjusting for age, exercise, smoking, BMI, systolic BP, triglyceride, and fasting glucose, these incidences were only increased between the lowest and the highest hs-CRP categories. The risk for NAFLD increased as the hs-CRP level increased (p< 0.001. As the hs-CRP level increased within the healthy cohort, the risk of developing NAFLD increased. This trend remained true even if the hs-CRP level remained within the normal range. hs-CRP can be used as a predictor of NAFLD, as well as other obesity-associated diseases. Therefore, individuals with higher hs-CRP levels (even within the normal range may require appropriate follow-up and management to prevent NAFLD development.

FdC1 and Leaf-Type Ferredoxins Channel Electrons From Photosystem I to Different Downstream Electron Acceptors.

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Guan, Xiaoqian; Chen, Shuai; Voon, Chia Pao; Wong, Kam-Bo; Tikkanen, Mikko; Lim, Boon L

2018-01-01

Plant-type ferredoxins in Arabidopsis transfer electrons from the photosystem I to multiple redox-driven enzymes involved in the assimilation of carbon, nitrogen, and sulfur. Leaf-type ferredoxins also modulate the switch between the linear and cyclic electron routes of the photosystems. Recently, two novel ferredoxin homologs with extra C-termini were identified in the Arabidopsis genome (AtFdC1, AT4G14890; AtFdC2, AT1G32550). FdC1 was considered as an alternative electron acceptor of PSI under extreme ferredoxin-deficient conditions. Here, we showed that FdC1 could interact with some, but not all, electron acceptors of leaf-type Fds, including the ferredoxin-thioredoxin reductase (FTR), sulfite reductase (SiR), and nitrite reductase (NiR). Photoreduction assay on cytochrome c and enzyme assays confirmed its capability to receive electrons from PSI and donate electrons to the Fd-dependent SiR and NiR but not to the ferredoxin-NADP + oxidoreductase (FNR). Hence, FdC1 and leaf-type Fds may play differential roles by channeling electrons from photosystem I to different downstream electron acceptors in photosynthetic tissues. In addition, the median redox potential of FdC1 may allow it to receive electrons from FNR in non-photosynthetic plastids.

Pretransplant Levels of CRP and Interleukin-6 Family Cytokines; Effects on Outcome after Allogeneic Stem Cell Transplantation

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Tor Henrik Tvedt

2016-11-01

Full Text Available Several pretransplant factors, including CRP (C-reactive protein levels, reflect the risk of complications after allogeneic stem cell transplantation. IL-6 induces CRP increase, and we therefore investigated the effects of pretransplant IL-6, soluble IL-6 receptors, IL-6 family cytokines and CRP serum levels on outcome for 100 consecutive allotransplant recipients. All patients had related donors, none had active infections and 99 patients were in complete remission before conditioning. The incidence of acute graft versus host disease (aGVHD requiring treatment was 40%, survival at Day +100 82%, and overall survival 48%. Despite a significant correlation between pretransplant CRP and IL-6 levels, only CRP levels significantly influenced transplant-related mortality (TRM. However, CRP did not influence overall survival (OS. Pretransplant IL-31 influenced late TRM. Finally, there was a significant association between pretransplant IL-6 and early postconditioning weight gain (i.e., fluid retention, and this fluid retention was a risk factor for aGVHD, TRM and OS. To conclude, pretransplant CRP, IL-31 and early posttransplant fluid retention were independent risk factors for TRM and survival after allotransplantation.

Identification of a novel centrosomal protein CrpF46 involved in cell cycle progression and mitosis

International Nuclear Information System (INIS)

Wei Yi; Shen Enzhi; Zhao Na; Liu Qian; Fan Jinling; Marc, Jan; Wang Yongchao; Sun Le; Liang Qianjin

2008-01-01

A novel centrosome-related protein Crp F46 was detected using a serum F46 from a patient suffering from progressive systemic sclerosis. We identified the protein by immunoprecipitation and Western blotting followed by tandem mass spectrometry sequencing. The protein Crp F46 has an apparent molecular mass of ∼ 60 kDa, is highly homologous to a 527 amino acid sequence of the C-terminal portion of the protein Golgin-245, and appears to be a splice variant of Golgin-245. Immunofluorescence microscopy of synchronized HeLa cells labeled with an anti-Crp F46 monoclonal antibody revealed that Crp F46 localized exclusively to the centrosome during interphase, although it dispersed throughout the cytoplasm at the onset of mitosis. Domain analysis using Crp F46 fragments in GFP-expression vectors transformed into HeLa cells revealed that centrosomal targeting is conferred by a C-terminal coiled-coil domain. Antisense Crp F46 knockdown inhibited cell growth and proliferation and the cell cycle typically stalled at S phase. The knockdown also resulted in the formation of poly-centrosomal and multinucleate cells, which finally became apoptotic. These results suggest that Crp F46 is a novel centrosome-related protein that associates with the centrosome in a cell cycle-dependent manner and is involved in the progression of the cell cycle and M phase mechanism

Clinical significance of determination of serum SA, CEA and CRP levels in patients with colo-rectal cancer

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Cai Jie; Hu Junyan; Sun Shuming; Cheng Benkun

2007-01-01

Objective: To investigate the clinical usefulness of determination of serum SA, CEA and CRP levels in patients with colorectal cancer. Methods: Serum SA (with colorimetry), CEA (with CLIA) and CRP (with ILIA) levels were measured in 120 patients with colo-rectal cancer. Results: (1) Serum SA, CEA and CRP levels increased significantly as the disease stage advanced from Duke A through Duke D. (2) As the malignancy of the growth advanced from well-differentiated to anaplastic, the serum SA and CRP levels increased significantly while the reverse was true for serum CEA levels. (3) In 68 post-operative patients followed 1-5 years, the serum levels of SA, CEA and CRP were significantly higher in the patients with recurrence (n=29) than those in patients without recurrence (n=39) (P<0.01). Conclusion: Serum SA CEA and CRP levels were closely related to the disease process in patients with colo-rectal cancer. (authors)

Threat-related amygdala activity is associated with peripheral CRP concentrations in men but not women

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Swartz, Johnna R.; Prather, Aric A.; Hariri, Ahmad R.

2017-01-01

Increased levels of peripheral inflammatory markers, including C-Reactive Protein (CRP), are associated with increased risk for depression, anxiety, and suicidality. The brain mechanisms that may underlie the association between peripheral inflammation and internalizing problems remain to be determined. The present study examines associations between peripheral CRP concentrations and threat-related amygdala activity, a neural biomarker of depression and anxiety risk, in a sample of 172 young adult undergraduate students. Participants underwent functional MRI scanning while performing an emotional face matching task to obtain a measure of threat-related amygdala activity to angry and fearful faces; CRP concentrations were assayed from dried blood spots. Results indicated a significant interaction between CRP and sex: in men, but not women, higher CRP was associated with higher threat-related amygdala activity. These results add to the literature finding associations between systemic levels of inflammation and brain function and suggest that threat-related amygdala activity may serve as a potential pathway through which heightened chronic inflammation may increase risk for mood and anxiety problems. PMID:28183031

Azcatl-CRP: An ant colony-based system for searching full power control rod patterns in BWRs

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Ortiz, Juan Jose [Dpto. Sistemas Nucleares, ININ, Carr. Mexico-Toluca Km. 36.5, Salazar, Edo. de Mexico (Mexico)]. E-mail: jjortiz@nuclear.inin.mx; Requena, Ignacio [Dpto. Ciencias Computacion e I.A. ETSII Informatica, University of Granada, C. Daniel Saucedo Aranda s/n, 18071 Granada (Spain)]. E-mail: requena@decsai.ugr.es

2006-01-15

We show a new system named AZCATL-CRP to design full power control rod patterns in BWRs. Azcatl-CRP uses an ant colony system and a reactor core simulator for this purpose. Transition and equilibrium cycles of Laguna Verde Nuclear Power Plant (LVNPP) reactor core in Mexico were used to test Azcatl-CRP. LVNPP has 109 control rods grouped in four sequences and currently uses control cell core (CCC) strategy in its fuel reload design. With CCC method only one sequence is employed for reactivity control at full power operation. Several operation scenarios are considered, including core water flow variation throughout the cycle, target different axial power distributions and Haling conditions. Azcatl-CRP designs control rod patterns (CRP) taking into account safety aspects such as k {sub eff} core value and thermal limits. Axial power distributions are also adjusted to a predetermined power shape.

Enterovirus type 71 2A protease functions as a transcriptional activator in yeast

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Lai Meng-Jiun

2010-08-01

Full Text Available Abstract Enterovirus type 71 (EV71 2A protease exhibited strong transcriptional activity in yeast cells. The transcriptional activity of 2A protease was independent of its protease activity. EV71 2A protease retained its transcriptional activity after truncation of 40 amino acids at the N-terminus but lost this activity after truncation of 60 amino acids at the N-terminus or deletion of 20 amino acids at the C-terminus. Thus, the acidic domain at the C-terminus of this protein is essential for its transcriptional activity. Indeed, deletion of amino acids from 146 to 149 (EAME in this acidic domain lost the transcriptional activity of EV71 2A protein though still retained its protease activity. EV71 2A protease was detected both in the cytoplasm and nucleus using confocal microscopy analysis. Coxsackie virus B3 2A protease also exhibited transcriptional activity in yeast cells. As expected, an acidic domain in the C-terminus of Coxsackie virus B3 2A protease was also identified. Truncation of this acidic domain resulted in the loss of transcriptional activity. Interestingly, this acidic region of poliovirus 2A protease is critical for viral RNA replication. The transcriptional activity of the EV71 or Coxsackie virus B3 2A protease should play a role in viral replication and/or pathogenesis.

Carbon debt of Conservation Reserve Program (CRP) grasslands converted to bioenergy production.

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Gelfand, Ilya; Zenone, Terenzio; Jasrotia, Poonam; Chen, Jiquan; Hamilton, Stephen K; Robertson, G Philip

2011-08-16

Over 13 million ha of former cropland are enrolled in the US Conservation Reserve Program (CRP), providing well-recognized biodiversity, water quality, and carbon (C) sequestration benefits that could be lost on conversion back to agricultural production. Here we provide measurements of the greenhouse gas consequences of converting CRP land to continuous corn, corn-soybean, or perennial grass for biofuel production. No-till soybeans preceded the annual crops and created an initial carbon debt of 10.6 Mg CO(2) equivalents (CO(2)e)·ha(-1) that included agronomic inputs, changes in C stocks, altered N(2)O and CH(4) fluxes, and foregone C sequestration less a fossil fuel offset credit. Total debt, which includes future debt created by additional changes in soil C stocks and the loss of substantial future soil C sequestration, can be constrained to 68 Mg CO(2)e·ha(-1) if subsequent crops are under permanent no-till management. If tilled, however, total debt triples to 222 Mg CO(2)e·ha(-1) on account of further soil C loss. Projected C debt repayment periods under no-till management range from 29 to 40 y for corn-soybean and continuous corn, respectively. Under conventional tillage repayment periods are three times longer, from 89 to 123 y, respectively. Alternatively, the direct use of existing CRP grasslands for cellulosic feedstock production would avoid C debt entirely and provide modest climate change mitigation immediately. Incentives for permanent no till and especially permission to harvest CRP biomass for cellulosic biofuel would help to blunt the climate impact of future CRP conversion.

cAMP-CRP acts as a key regulator for the viable but non-culturable state in Escherichia coli.

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Nosho, Kazuki; Fukushima, Hiroko; Asai, Takehiro; Nishio, Masahiro; Takamaru, Reiko; Kobayashi-Kirschvink, Koseki Joseph; Ogawa, Tetsuhiro; Hidaka, Makoto; Masaki, Haruhiko

2018-03-01

A variety of bacteria, including Escherichia coli, are known to enter the viable but non-culturable (VBNC) state under various stress conditions. During this state, cells lose colony-forming activities on conventional agar plates while retaining signs of viability. Diverse environmental stresses including starvation induce the VBNC state. However, little is known about the genetic mechanism inducing this state. Here, we aimed to reveal the genetic determinants of the VBNC state of E. coli. We hypothesized that the VBNC state is a process wherein specific gene products important for colony formation are depleted during the extended period of stress conditions. If so, higher expression of these genes would maintain colony-forming activities, thereby restraining cells from entering the VBNC state. From an E. coli plasmid-encoded ORF library, we identified genes that were responsible for maintaining high colony-forming activities after exposure to starvation condition. Among these, cpdA encoding cAMP phosphodiesterase exhibited higher performance in the maintenance of colony-forming activities. As cpdA overexpression decreases intracellular cAMP, cAMP or its complex with cAMP-receptor protein (CRP) may negatively regulate colony-forming activities under stress conditions. We confirmed this using deletion mutants lacking adenylate cyclase or CRP. These mutants fully maintained colony-forming activities even after a long period of starvation, while wild-type cells lost most of this activity. Thus, we concluded that the lack of cAMP-CRP effectively retains high colony-forming activities, indicating that cAMP-CRP acts as a positive regulator necessary for the induction of the VBNC state in E. coli.

Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells.

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Wang, Xiuling; Liu, Zhongchun; Wang, Peigang; Li, Shan; Zeng, Jie; Tu, Xiaoning; Yan, Qiujin; Xiao, Zheman; Pan, Mengxian; Zhu, Fan

2018-01-01

Schizophrenia is a devastating psychiatric disorder that impacts on social functioning and quality of life, and there is accumulating evidence that inflammation is a potential pathogenic mechanism of schizophrenia. However, the mechanism of inflammation possibly occurred in schizophrenia has not been well understood. The endogenous retroviral protein syncytin-1 and inflammatory marker CRP are both abnormally expressed in schizophrenia patients. CRP is one of the markers of bacterial infection generally. Less clear is whether virus or viral protein can trigger the activation of CRP. Here, we detected a robust increase of the levels of syncytin-1 and CRP in schizophrenia patients, and displayed a positive correlation and marked consistency between expressions of syncytin-1 and CRP in schizophrenia patients. Furthermore, overexpression of syncytin-1 significantly elevated the levels of CRP, TLR3, and IL-6 in both human microglia and astrocytes. TLR3 deficiency impaired the expressions of CRP and IL-6 induced by syncytin-1. Importantly, we observed a cellular co-localization and a direct interaction between syncytin-1 and TLR3. Additionally, knockdown of IL-6 inhibited the syncytin-1-induced CRP expression. Thus, the totality of these results showed that viral protein syncytin-1 could trigger the activation of CRP, which might explain the elevated CRP in sterile inflammation and exhibit a novel mechanism for regulation of inflammation by syncytin-1 in schizophrenia. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

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Mazidi, Mohsen; Karimi, Ehsan; Rezaie, Peyman; Ferns, Gordon A

2017-07-01

To undertake a systematic review and meta-analysis of randomized controlled trials of the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy on serum C-reactive protein (CRP) concentrations. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched for the period up until March 16, 2016. Prospective studies evaluating the impact of GLP-1 RAs on serum CRP were identified. A random effects model (using the DerSimonian-Laird method) and generic inverse variance methods were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I 2 index. Random effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential moderator. International Prospective Register for Systematic Reviews (PROSPERO) number CRD42016036868. Meta-analysis of the data from 7 treatment arms revealed a significant reduction in serum CRP concentrations following treatment with GLP-1 RAs (WMD -2.14 (mg/dL), 95% CI -3.51, -0.78, P=0.002; I 2 96.1%). Removal of one study in the meta-analysis did not change the result in the sensitivity analysis (WMD -2.14 (mg/dL), 95% CI -3.51, -0.78, P=0.002; I 2 96.1%), indicating that our results could not be solely attributed to the effect of a single study. Random effects meta-regression was performed to evaluate the impact of potential moderator on the estimated effect size. Changes in serum CRP concentration were associated with the duration of treatment (slope -0.097, 95% CI -0.158, -0.042, Pmeta-analysis suggests that GLP-1 RAs therapy causes a significant reduction in CRP. Copyright © 2016 Elsevier Inc. All rights reserved.

CRP and SAA1 Haplotypes Are Associated with Both C-Reactive Protein and Serum Amyloid A Levels: Role of Suppression Effects

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Yu-Lin Ko

2016-01-01

Full Text Available To test the statistical association of the CRP and SAA1 locus variants with their corresponding circulating levels and metabolic and inflammatory biomarker levels by using mediation analysis, a sample population of 599 Taiwanese subjects was enrolled and five CRP and four SAA1 variants were genotyped. Correlation analysis revealed that C-reactive protein (CRP and serum amyloid A (SAA levels were significantly associated with multiple metabolic phenotypes and inflammatory marker levels. Our data further revealed a significant association of CRP and SAA1 variants with both CRP and SAA levels. Mediation analysis revealed that SAA levels suppressed the association between SAA1 genotypes/haplotypes and CRP levels and that CRP levels suppressed the association between CRP haplotypes and SAA levels. In conclusion, genetic variants at the CRP and SAA1 loci independently affect both CRP and SAA levels, and their respective circulating levels act as suppressors. These results provided further evidence of the role of the suppression effect in biological science and may partially explain the missing heritability in genetic association studies.

Changes of BNP, ANP, ET and CRP levels in the plasma of patients with acute myocardial infarction

International Nuclear Information System (INIS)

Du Tongxing; Wang Zizheng; Wang Shukui; Luo Jun

2004-01-01

To explore the pathogenesis and provide evidence for the diagnosis, therapy and prognosis of acute myocardial infarction (AMI) by observing the levels of brain natriuretic peptide (BNP), endothelins (ET), C-reactive protein (CRP) and atrial natriuretic peptide (ANP) in plasma of the patients, BNP, ET, CRP and ANP levels in plasma of 46 AMI patients before and after therapy and 30 normal controls were detected by ELISA and immunoradiometric assay, respectively. Results showed that there were significant differences in BNP, ET, CRP and ANP levels in patients with AMI before and after therapy (P 0.05) after thrombolysis and other supporting therapy, the decreased BNP, ET and CRP were still significantly higher than those of control ( P<0.05). The changes of BNP, ANP, ET and CRP indicate that they involved in the occurrence and development of AMI, especially in the formation and disruption of atheromatous plaque and thrombosis. So the detection of BNP, ANP, ET and CRP levels was significant to the diagnosis, therapy and prognosis judgement

Clinical significance of determination of the levels of serum IL-6, TNF-α and hs-CRP in patients with DM2 complicated with coronary heart disease (CHD)

International Nuclear Information System (INIS)

Li Juan; Zhao Qian; Zhang Dajun

2007-01-01

Objective: To investigate the significance of changes of serum IL-6, TNF-α, hs-CRP levels in development of coronary heart disease in patients with type 2 diabetes mellitus. Methods: Serum IL-6, TNF-α (with RIA). hs-CRP (with CLIA) and FPG, TG, cholesterol (with biochemistry) contents were measured in (1) DM2 patients complicated with CHD, n=40 and (2) DlVI2 patients without CHD, n=48. Results: The BMI and FPG, TG levels were significantly higher in patients complicated with heart disease than those in patients without CHD (P<0.05) with the exception of cholesterol. The levels of IL-6, TNF-α and hs-CRP were also significantly higher in patients with heart disease than those in patients without heart disease (P<0.05). Conclusion: The high levels of IL-6, TNF-α and hs-CRP played important role in the development of coronary heart disease. Monitoring those levels might be helpful in assessment of treatment efficacy and outcome prediction. (authors)

Gly184 of the Escherichia coli cAMP receptor protein provides optimal context for both DNA binding and RNA polymerase interaction.

Science.gov (United States)

Hicks, Matt N; Gunasekara, Sanjiva; Serate, Jose; Park, Jin; Mosharaf, Pegah; Zhou, Yue; Lee, Jin-Won; Youn, Hwan

2017-10-01

The Escherichia coli cAMP receptor protein (CRP) utilizes the helix-turn-helix motif for DNA binding. The CRP's recognition helix, termed F-helix, includes a stretch of six amino acids (Arg180, Glu181, Thr182, Val183, Gly184, and Arg185) for direct DNA contacts. Arg180, Glu181 and Arg185 are known as important residues for DNA binding and specificity, but little has been studied for the other residues. Here we show that Gly184 is another F-helix residue critical for the transcriptional activation function of CRP. First, glycine was repeatedly selected at CRP position 184 for its unique ability to provide wild type-level transcriptional activation activity. To dissect the glycine requirement, wild type CRP and mutants G184A, G184F, G184S, and G184Y were purified and their in vitro DNA-binding activity was measured. G184A and G184F displayed reduced DNA binding, which may explain their low transcriptional activation activity. However, G184S and G184Y displayed apparently normal DNA affinity. Therefore, an additional factor is needed to account for the diminished transcriptional activation function in G184S and G184Y, and the best explanation is perturbations in their interaction with RNA polymerase. The fact that glycine is the smallest amino acid could not fully warrant its suitability, as shown in this study. We hypothesize that Gly184 fulfills the dual functions of DNA binding and RNA polymerase interaction by conferring conformational flexibility to the F-helix.

The 52Cr(p, γ)53Mn reaction

NARCIS (Netherlands)

Vuister, P.H.

The 52Cr(p, γ)53Mn reaction was investigated in the energy region Ep = 1.36–2.26 MeV. The resonance energies, the corresponding 53Mn excitation energies and the resonance strengths of 199 resonances, assigned to this reaction, are reported. The excitation energies and gamma-ray branchings of 13

Correlation between Serum High Sensitivity CRP Level and Inhospital Cardiac Events in the Patients with Unstable Angina

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H. Kazerani

2007-10-01

Full Text Available Introduction & Objective: Several studies have been performed to evaluate correlation of serum high sensitivity CRP (hs-CRP level with the prognosis of the patients with diagnosis of unstable angina, and by now different results were reported. The aim of this study was to assess correlation between serum hs-CRP level and inhospital prognosis and cardiac events in the patients with unstable angina. Materials & Methods: This descriptive analytic study was performed from Sep 2004 till Feb 2006 in Shahid Beheshti hospital. Kermanshah, Iran. Sera were collected from 250 patients for hs-CRP measurement. Exclusion criteria were: acute ST elevation MI, non ST elevation MI, patients with history of recent infection, patients with recent trauma and patients with serum high sensitive CRP level more than 10 mg/lit. Patients were divided into two groups, first group whose serum hs-CRP level was less than 3 mg/lit and second group whose serum hs-CRP level was between 3 and 10 mg/lit. They were followed for recurrent chest pain, arrhythmias, pulmonary edema, acute myocardial infarction and in hospital death. Results were analyzed using x² and t-test. Results: Mean age were 57±7.8 and 58±11.5 years in first group and second group respectively. There was statistically significant difference in some cardiac complications such as dyspnea, duration of hospitalization, recurrent chest pain, CCU admission (p<0.001 and in hospital myocardial infarction (p=0.03, between two groups. Some complications did not have significant difference such as pulmonary edema, cardiogenic shock, arrhythmia, S3, S4 and pulmonary rates .There was no mortality in both groups. Conclusion: According to the results, we can use serum hs-CRP level for risk stratification in the patients with diagnosis of unstable angina. Obviously the patients with high serum hs-CRP level need more attention whether early invasive management help these patients, may be the matter of later studies.

IAEA coordinated research project (CRP) on 'Analytical and experimental benchmark analyses of accelerator driven systems'

International Nuclear Information System (INIS)

Abanades, Alberto; Aliberti, Gerardo; Gohar, Yousry; Talamo, Alberto; Bornos, Victor; Kiyavitskaya, Anna; Carta, Mario; Janczyszyn, Jerzy; Maiorino, Jose; Pyeon, Cheolho; Stanculescu, Alexander; Titarenko, Yury; Westmeier, Wolfram

2008-01-01

In December 2005, the International Atomic Energy Agency (IAEA) has started a Coordinated Research Project (CRP) on 'Analytical and Experimental Benchmark Analyses of Accelerator Driven Systems'. The overall objective of the CRP, performed within the framework of the Technical Working Group on Fast Reactors (TWGFR) of IAEA's Nuclear Energy Department, is to increase the capability of interested Member States in developing and applying advanced reactor technologies in the area of long-lived radioactive waste utilization and transmutation. The specific objective of the CRP is to improve the present understanding of the coupling of an external neutron source (e.g. spallation source) with a multiplicative sub-critical core. The participants are performing computational and experimental benchmark analyses using integrated calculation schemes and simulation methods. The CRP aims at integrating some of the planned experimental demonstration projects of the coupling between a sub-critical core and an external neutron source (e.g. YALINA Booster in Belarus, and Kyoto University's Critical Assembly (KUCA)). The objective of these experimental programs is to validate computational methods, obtain high energy nuclear data, characterize the performance of sub-critical assemblies driven by external sources, and to develop and improve techniques for sub-criticality monitoring. The paper summarizes preliminary results obtained to-date for some of the CRP benchmarks. (authors)

Belgian Contribution to the IAEA CRP-IV Programme on Assuring Structural Integrity of Reactor Pressure Vessel

International Nuclear Information System (INIS)

Van Walle, E.; Chaouadi, R.; Scibetta, M.; Puzzolante, J.L.; Fabry, A.; Van de Velde, J.

1997-10-01

This report contains the actual status of the Belgian contribution to the IAEA CRP-IV program. Besides Charpy-V impact tests on as-received CRP-IV JRQ-specimens, fracture toughness tests were performed on two geometries: PCCV-specimens and CRB-specimens. The Charpy-V impact results correspond very well with the as-received CRP-III results. The fracture toughness data are also very consistent with identical tests recently performed on remaining as-received CRP-III material. Irradiated broken Charpy-V samples were reconstituted and tested in PCCV-mode. This was done in order to investigate the evolution of the ASME-curve versus the evolution of the mastercurve with irradiation. Initial results were reported. A new CHIVAS-irradiation in the CALLISTO-loop of the BR-2-reactor to support this investigation, is under preparation

Failure of CRP decline within three days of hospitalization is associated with poor prognosis of Community-acquired Pneumonia

DEFF Research Database (Denmark)

Andersen, Stine Bang; Baunbæk Egelund, Gertrud Louise; Jensen, Andreas Vestergaard

2017-01-01

BACKGROUND: C-reactive protein (CRP) is a well-known acute phase protein used to monitor the patient's response during treatment in infectious diseases. Mortality from Community-acquired Pneumonia (CAP) remains high, particularly in hospitalized patients. Better risk prediction during hospitaliza......BACKGROUND: C-reactive protein (CRP) is a well-known acute phase protein used to monitor the patient's response during treatment in infectious diseases. Mortality from Community-acquired Pneumonia (CAP) remains high, particularly in hospitalized patients. Better risk prediction during...... hospitalization could improve management and ultimately reduce mortality levels. The aim of this study was to evaluate CRP on the 3rd day (CRP3) of hospitalization as a predictor for 30 days mortality. METHODS: A retrospective multicentre cohort study of adult patients admitted with CAP at three Danish hospitals....... Predictive associations of CRP3 (absolute levels and relative decline) and 30 days mortality were analysed using receiver operating characteristics and logistic regression. RESULTS: Eight hundred and fourteen patients were included and 90 (11%) died within 30 days. The area under the curve for CRP3 level...

Clinical significance of changes of plasma TNF-α and CRP levels in patients with acute cerebral infarction

International Nuclear Information System (INIS)

Liu Xiaoyang; Xiao Changqing; He Yunnan

2006-01-01

Objective: To investigate the clinical significance of the changes of serum TNF-α and CRP levels in patients with acute cerebral infarction. Methods: Serum TNF-α (with RIA) and CRP (with scatter velocity turbidimetry) levels were determined in 50 patients with acute cerebral infarction and 62 controls. Results: The serum levels of TNF-α and CRP in patients with acute cerebral infarction were significantly higher than those in controls (P <0.01). Moreover, the levels were positively correlated with the size of the infarction (P<0.05). Conclusion: Changes of serum TNF-α and CRP levels during acute stage of cerebral infarction were closely related the clinical progression of the disease process. (authors)

Contributions to and expectations from the CRP - Argonne National Laboratory (USA)

International Nuclear Information System (INIS)

Cahalan, J.E.

2007-01-01

For us, the chief benefit of the CRP will be validation of multidimensional fluid dynamics capabilities for analysis of outlet plenum temperature distributions. As reactor designers seek new fuel handling features to reduce costs, upper internal structure configurations are becoming more compact, and higher fidelity analysis techniques are required to assess thermal stresses. Argonne currently has 1) a reactor systems analysis code with an experimentally-based model for plenum stratification, 2) the COMMIX code (parent of the JAEA AQUA code), and 3) commercial fluid dynamics analysis codes. It is anticipated that all or some combination of these capabilities will be employed to perform the CRP analysis

A robust quantitative solid phase immunoassay for the acute phase protein C-reactive protein (CRP) based on cytidine 5 '-diphosphocholine coupled dendrimers

DEFF Research Database (Denmark)

Heegaard, Peter M. H.; Pedersen, H. G.; Jensen, A. L.

2009-01-01

C-reactive protein (CRP) is an important acute phase protein, being used as a sensitive indicator of inflammation and infection and is also associated with the risk of cardiovascular problems. The present paper describes a robust and sensitive ELISA for CRP, based on the affinity of CRP for phosp......C-reactive protein (CRP) is an important acute phase protein, being used as a sensitive indicator of inflammation and infection and is also associated with the risk of cardiovascular problems. The present paper describes a robust and sensitive ELISA for CRP, based on the affinity of CRP...... was applied to determination of pig and human CRP using commercially available antibodies against human CRP. The assay was shown to be more sensitive than previously published immunoassays employing albumin-coupled cytidine diphosphocholine. The coating was stable for at least 30 days at room temperature...

The Value of HbA1c and hs-CRP Combined Detection in Diagnosis of Diabetic Retinopathy%HbA1c、hs-CRP 联合检测诊断糖尿病视网膜病变的价值

Institute of Scientific and Technical Information of China (English)

李孝才; 孙学芬; 吴建霞; 马雪燕

2016-01-01

目的：探讨糖化血红蛋白（HbA1c）和高敏 C 反应蛋白（hs-CRP）联合检测诊断糖尿病视网膜病变的价值。方法：选择正常体检者(A 组）、糖尿病无视网膜病变者(B 组）、糖尿病视网膜病变者(C 组）各72例，采用离子交换液相层析法和胶乳增强免疫比浊法测定 HbA1c 及 hs-CRP。结果：无视网膜病变组和视网膜病变组的 HbA1c 和 hs-CRP（mg/L）含量均比健康对照组高，具有统计学意义（P0.05）；但是 HbA1c +Hs-CRP 诊断糖尿病视网膜病变的特异为90.3%，分别与 HbA1c 和 hs-CRP 存在明显差异（P 0.05); but specific to the HbA1c of hs CRP in the diagnosis of diabetic retinopathy was 90.3%, respectively and hs CRP and HbA1c exist significant difference (P< 0.05). Conclusion:The detection of HBA1c and Hs-CRPis helpful to early detection of diabetic retinopathy, which can be used asmonitoring indicators for progress and treatment effect in type 2 diabetes mellitus patients.

Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms

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Wang Ena

2005-06-01

Full Text Available Abstract Background Interferon (IFN-α is considered a key modulator of immunopathological processes through a signature-specific activation of mononuclear phagocytes (MPs. This study utilized global transcript analysis to characterize the effects of the entire type I IFN family in comparison to a broad panel of other cytokines on MP previously exposed to Lipopolysaccharide (LPS stimulation in vitro. Results Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later with 42 separate soluble factors including cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four hours after stimulation, the transcriptional analysis of MPs revealed two main classes of cytokines: one associated with the alternative and the other with the classical pathway of MP activation without a clear polarization of type I IFNs effects. In contrast, after 9 hours of stimulation most type I IFN isoforms induced a characteristic and unique transcriptional pattern separate from other cytokines. These "signature" IFNs included; IFN-β, IFN-α2b/α2, IFN-αI, IFN-α2, IFN-αC, IFN-αJ1, IFN-αH2, and INF-α4B and induced the over-expression of 44 genes, all of which had known functional relationships with IFN such as myxovirus resistance (Mx-1, Mx-2, and interferon-induced hepatitis C-associated microtubular aggregation protein. A second group of type I IFNs segregated separately and in closer association with the type II IFN-γ. The phylogenetic relationship of amino acid sequences among type I IFNs did not explain their sub-classification, although differences at positions 94 through 109 and 175 through 189 were present between the signature and other IFNs. Conclusion Seven IFN-α isoforms and IFN-β participate in the late phase polarization of MPs conditioned by LPS. This information broadens the previous view of the central role played by IFN-α in

Composing a Tumor Specific Bacterial Promoter.

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Igor V Deyneko

Full Text Available Systemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules. Specificity of such delivery is solely depending on promoter sequences that control the production of a target molecule. We have established the functional structure of bacterial promoters that are transcriptionally active exclusively in tumor tissues after systemic application. We observed that the specific transcriptional activation is accomplished by a combination of a weak basal promoter and a strong FNR binding site. This represents a minimal set of control elements required for such activation. In natural promoters, additional DNA remodeling elements are found that alter the level of transcription quantitatively. Inefficiency of the basal promoter ensures the absence of transcription outside tumors. As a proof of concept, we compiled an artificial promoter sequence from individual motifs representing FNR and basal promoter and showed specific activation in a tumor microenvironment. Our results open possibilities for the generation of promoters with an adjusted level of expression of target proteins in particular for applications in bacterial tumor therapy.

Application value of Serum Hs-CRP, IL-6 and plasma FIB joint detection in COPD

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Feng Ji

2016-11-01

Full Text Available Objective: To discuss the application value of High sensitivity C-reactive protein (Hs-CRP, interleukin-6 (IL-6 and fibrinogen (FIB joint detection in chronic obstructive pulmonary disease (COPD. Methods: A total of 181 COPD cases were divided to be COPD stable phase group (65 cases and COPD acute exacerbation phase group (116 cases per the course of disease. COPD acute exacerbation phase group was classified into grade I (39 cases, grade II (43 cases and grade III (34 cases based on pulmonary function. Then survival group (87 cases and death group (29 cases were divided based on illness transition. Meanwhile, 80 cases of healthy people at the same phase were set to be healthy group. Differences in levels of Serum hs-CRP, IL-6 and FIB in these groups were analyzed, and according to these indexes, prognostic potency of COPD acute exacerbation phase could be evaluated. Results: Difference in serum hs-CRP, IL-6 and FIB levels in COPD stable phase group, COPD acute exacerbation phase group and healthy group were statistical significant (P<0.05. both for healthy group CRP, IL-6 and FIB levels in grade I, II, III of pulmonary function in the COPD acute exacerbation phase group were statistical significant (P<0.05 both for grade 1 < grade 2 < grade 3. Result of person analyzing showed significant positive correlation on grading of pulmonary function and serum hs-CRP, IL-6 and FIB levels, the correlation coefficient was 0.573. Differences of hs-CRP, IL-6 and FIB levels between survival group and death group were statistical significant. Serum hs-CRP, IL-6 and FIB levels were utilized respectively to evaluate area under curve of receiver operating characteristic in prognostic COPD acute exacerbation phase group, namely, 0.836, 0.815, 0.776. Sensitivities of “death”, which was evaluated by the various indexes, respectively showed as: 72.41%, 65.51% and 75

Effect of flurbiprofen aretilon on serum hs-CRP, IL-6 levels in patients undergoing esophageal cancer surgery

International Nuclear Information System (INIS)

Li Jiakai

2011-01-01

Objective: To investigate the effect of flurbiprofen axetil on serum high sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6) in the patients undergoing esophageal cancer surgery. Methods: Thirty patients were divided into 2 groups with 15 cases each. The patients in groups A were given flurbiprofen axetil and those in group B were not as the controls. Serum hs-CRP (immuno-turbidity method) and IL-6 (RIA) levels were determined before anesthesia induction and after extubation. Results: The levels of serum hs-CRP, IL-6 were significantly higher in group B than those in group A (P<0.05). Conclusion: Flurbiprofen axetil could reduce serum hs-CRP, IL-6 levels in patients undergoing Esophageal cancer surgery. (authors)

A Prospective Study to Compare the Diagnostic Value of Serum Procalcitonin and Crp in Early Onset Sepsis

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Suresh Kumar Verma

2017-10-01

Full Text Available Introduction: Neonatal sepsis is the most common cause of death in newborns in developing countries. Prompt diagnosis is the critical determinant in its outcome. As manifestations are often vague, clinically it is difficult to differentiate sepsis from non-infective conditions. Timely diagnosis is important as delay in initiation of antimicrobials can prove fatal. On the other hand empirical use of antibiotics not only increases the risk of antibiotic resistance but also delays the diagnosis of true condition. Procalcitonin (PCT has been well evaluated in late onset sepsis but data pertaining to Early Onset Sepsis (EOS are still lacking. We compared the diagnostic value of PCT and CRP (C-Reactive Protein in EOS. Aim: To compare the diagnostic value of serum PCT and CRP in early onset sepsis. Materials and Methods: It was a prospective observational study conducted in Neonatal Intensive Care Unit of the Department of Paediatrics, Dr.S.N. Medical College, Jodhpur, India. All neonates delivered in hospitals attached to this medical college or referred here within 7 days of life and having ≥2 perinatal risk factors for sepsis or displaying clinical sepsis were included in the study. All enrolled neonates were subjected to sepsis screen, PCT levels and blood culture at birth or admission which ever was the earliest. PCT levels ≥ 0.5 ng/ml and CRP levels above 8mg/l were considered positive for EOS. Results: Sensitivity and negative predictive value of PCT were higher than CRP (90.12% vs. 50.62% and 93.33% vs. 79.06% respectively. Also it had a higher positive predictive value of 40.56% than CRP where it was 37.61%. CRP was more specific (68.95% vs. 51.4% with overall higher diagnostic accuracy (0.64 vs. 0.61 in comparison to PCT. Conclusion: PCT is more sensitive and has a higher negative predictive value than CRP in early onset sepsis. Higher positive predictive value and specificity of CRP suggest that, PCT should not be used alone rather

Identification and characterization of a cluster of transcription start sites located in the E6 ORF of human papillomavirus type 16

DEFF Research Database (Denmark)

Rosenstierne, Maiken W; Vinther, Jeppe; Hansen, Christina N

2003-01-01

Human papillomavirus type 16 (HPV-16) is the prototype strain among the malignant types of HPV in the western world. The main promoter, P97, located in front of the E6 ORF, has been shown to control expression of the oncogenes E6 and E7. These oncogenes are expressed continuously in HPV-16......-transformed cells. In contrast to malignant HPV types, non-malignant HPV types have separate promoters driving the expression of E6 and E7. Experiments have shown that the translation of E7 is more efficient from monocistronic than bicistronic transcripts encoding both E6 and E7. Here, identification...... of a cluster of transcription start sites located in the E6 ORF of HPV-16 is presented. Transcripts from this region contain the E7 ORF as the first reading frame. The cluster consists of multiple transcription start sites located around nt 441. Additional transcription start sites were identified in a cluster...

Use of a computerized C-reactive protein (CRP based sepsis evaluation in very low birth weight (VLBW infants: a five-year experience.

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Sarah A Coggins

Full Text Available Serial C-reactive protein (CRP values may be useful for decision-making regarding duration of antibiotics in neonates. However, established standard of practice for its use in preterm very low birth weight (<1500 g, VLBW infants are lacking.Evaluate compliance with a CRP-guided computerized decision support (CDS algorithm and compare characteristics and outcomes of compliant versus non-compliant cases. Measure correlation between CRPs and white blood count (WBC indices.We examined 3 populations: 1 all preterm VLBW infants born at Vanderbilt 2006-2011 - we assessed provider compliance with CDS algorithm and measured relevant outcomes; 2 all patients with positive blood culture results admitted to the Vanderbilt NICU 2006-2012 - we tested the correlation between CRP and WBC results within 7 days of blood culture phlebotomy; 3 1,000 randomly selected patients out of the 7,062 patients admitted to the NICU 2006-2012 - we correlated time-associated CRP values and absolute neutrophil counts.Of 636 VLBW infants in cohort 1, 569 (89% received empiric antibiotics for suspected early-onset sepsis. In 409 infants (72% the CDS algorithm was followed; antibiotics were discontinued ≤48 hours in 311 (55% with normal serial CRPs and continued in 98 (17% with positive CRPs, resulting in significant reduction in antibiotic exposure (p<0.001 without increase in complications or subsequent infections. One hundred sixty (28% were considered non-compliant because antibiotics were continued beyond 48 hours despite negative serial CRPs and blood cultures. Serial CRPs remained negative in 38 (12% of 308 blood culture-positive infants from cohort 2, but only 4 patients had clinically probable sepsis with single organisms and no immunodeficiency besides extreme prematurity. Leukopenia of any cell type was not linked with CRPs in cohorts 2 and 3.CDS/CRP-guided antibiotic use is safe and effective in culture-negative VLBW infants. CRP results are not affected by low WBC

Translational regulation of gene expression by an anaerobically induced small non-coding RNA in Escherichia coli

DEFF Research Database (Denmark)

Boysen, Anders; Møller-Jensen, Jakob; Kallipolitis, Birgitte H.

2010-01-01

Small non-coding RNAs (sRNA) have emerged as important elements of gene regulatory circuits. In enterobacteria such as Escherichia coli and Salmonella many of these sRNAs interact with the Hfq protein, an RNA chaperone similar to mammalian Sm-like proteins and act in the post...... that adaptation to anaerobic growth involves the action of a small regulatory RNA....... of at least one sRNA regulator. Here, we extend this view by the identification and characterization of a highly conserved, anaerobically induced small sRNA in E. coli, whose expression is strictly dependent on the anaerobic transcriptional fumarate and nitrate reductase regulator (FNR). The sRNA, named Fnr...

Transcriptional and metabolic response of recombinant Escherichia coli to spatial dissolved oxygen tension gradients simulated in a scale-down system.

Science.gov (United States)

Lara, Alvaro R; Leal, Lidia; Flores, Noemí; Gosset, Guillermo; Bolívar, Francisco; Ramírez, Octavio T

2006-02-05

Escherichia coli, expressing recombinant green fluorescent protein (GFP), was subjected to dissolved oxygen tension (DOT) oscillations in a two-compartment system for simulating gradients that can occur in large-scale bioreactors. Cells were continuously circulated between the anaerobic (0% DOT) and aerobic (10% DOT) vessels of the scale-down system to mimic an overall circulation time of 50 s, and a mean residence time in the anaerobic and aerobic compartments of 33 and 17 s, respectively. Transcription levels of mixed acid fermentation genes (ldhA, poxB, frdD, ackA, adhE, pflD, and fdhF), measured by quantitative RT-PCR, increased between 1.5- to over 6-fold under oscillatory DOT compared to aerobic cultures (constant 10% DOT). In addition, the transcription level of fumB increased whereas it decreased for sucA and sucB, suggesting that the tricarboxylic acid cycle was functioning as two open branches. Gene transcription levels revealed that cytrochrome bd, which has higher affinity to oxygen but lower energy efficiency, was preferred over cytochrome bO3 in oscillatory DOT cultures. Post-transcriptional processing limited heterologous protein production in the scale-down system, as inferred from similar gfp transcription but 19% lower GFP concentration compared to aerobic cultures. Simulated DOT gradients also affected the transcription of genes of the glyoxylate shunt (aceA), of global regulators of aerobic and anaerobic metabolism (fnr, arcA, and arcB), and other relevant genes (luxS, sodA, fumA, and sdhB). Transcriptional changes explained the observed alterations in overall stoichiometric and kinetic parameters, and production of ethanol and organic acids. Differences in transcription levels between aerobic and anaerobic compartments were also observed, indicating that E. coli can respond very fast to intermittent DOT conditions. The transcriptional responses of E. coli to DOT gradients reported here are useful for establishing rational scale-up criteria and

Determining the control circuitry of redox metabolism at the genome-scale.

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Stephen Federowicz

2014-04-01

Full Text Available Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs, ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r(2 (p<1e-6 correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. Finally, we are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.

Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation

DEFF Research Database (Denmark)

Hakim-Weber, Robab; Krogsdam, Anne-M; Jørgensen, Claus

2011-01-01

Although many molecular regulators of adipogenesis have been identified a comprehensive catalogue of components is still missing. Recent studies showed that the retinoblastoma protein (pRb) was expressed in the cell cycle and late cellular differentiation phase during adipogenesis. To investigate...... this dual role of pRb in the early and late stages of adipogenesis we used microarrays to perform a comprehensive systems-level analysis of the common transcriptional program of the classic 3T3-L1 preadipocyte cell line, wild-type mouse embryonic fibroblasts (MEFs), and retinoblastoma gene-deficient MEFs...... of experimental data and computational analyses pinpointed a feedback-loop between Pparg and Foxo1.To analyze the effects of the retinoblastoma protein at the transcriptional level we chose a perturbated system (Rb-/- MEFs) for comparison to the transcriptional program of wild-type MEFs. Gene ontology analysis...

Clinical diagnostic value of determination of plasma ET, Hcy and serum hs-CRP contents in patients with coronary heart diseases

International Nuclear Information System (INIS)

Chu Jingying; Zhu Xueming

2008-01-01

Objective: To study the clinical diagnostic value of determination of plasma ET, Hcy and serum hs-CRP contents in patients with coronary heart disease (CHD). Methods: Plasma ET, Hcy(with RIA) and serum hs-CRP (with immune turbidimetry) contents were determined in 38 patients with CHD and 35 controls. Results: Plasma ET, Hcy and serum hs-CRP concentration were significantly higher in CHD patients (than those in controls P<0.01). Plasma ET levels were significantly positively correlated with those of plasma Hcy and serum hs-CRP (r=0.6122, 0.5842, P<0.01). Conclusion: Detection of changes of plasma ET, Hcy and serum hs-CRP levels might be of prognostic importance in patients with CHD. (authors)

Distinct physiological roles for the two L-asparaginase isozymes of Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Srikhanta, Yogitha N. [Department of Microbiology and Immunology, The University of Melbourne, Victoria 3010 (Australia); Atack, John M.; Beacham, Ifor R. [Institute for Glycomics, Griffith University, Gold Coast, QLD 4222 (Australia); Jennings, Michael P., E-mail: m.jennings@griffith.edu.au [Institute for Glycomics, Griffith University, Gold Coast, QLD 4222 (Australia)

2013-07-05

Highlights: •Escherichia coli contains two L-asparaginase isozymes with distinct localization, kinetics and regulation. •Mutant strains were used to examine the roles of these enzymes in L-asparagine utilization. •We report that L-asparaginase II permits growth on asparagine and glycerol under anaerobic conditions. •We propose that this enzyme is the first step in a co-regulated pathway leading to fumarate. •The pathway is regulated by anaerobiosis and cAMP and provides a terminal elector acceptor. -- Abstract: Escherichia coli expresses two L-asparaginase (EC 3.5.1.1) isozymes: L-asparaginse I, which is a low affinity, cytoplasmic enzyme that is expressed constitutively, and L-asparaginase II, a high affinity periplasmic enzyme that is under complex co-transcriptional regulation by both Fnr and Crp. The distinct localisation and regulation of these enzymes suggest different roles. To define these roles, a set of isogenic mutants was constructed that lacked either or both enzymes. Evidence is provided that L-asparaginase II, in contrast to L-asparaginase I, can be used in the provision of an anaerobic electron acceptor when using a non-fermentable carbon source in the presence of excess nitrogen.

Cell-type specificity of ChIP-predicted transcription factor binding sites

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Håndstad Tony

2012-08-01

Full Text Available Abstract Background Context-dependent transcription factor (TF binding is one reason for differences in gene expression patterns between different cellular states. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identifies genome-wide TF binding sites for one particular context—the cells used in the experiment. But can such ChIP-seq data predict TF binding in other cellular contexts and is it possible to distinguish context-dependent from ubiquitous TF binding? Results We compared ChIP-seq data on TF binding for multiple TFs in two different cell types and found that on average only a third of ChIP-seq peak regions are common to both cell types. Expectedly, common peaks occur more frequently in certain genomic contexts, such as CpG-rich promoters, whereas chromatin differences characterize cell-type specific TF binding. We also find, however, that genotype differences between the cell types can explain differences in binding. Moreover, ChIP-seq signal intensity and peak clustering are the strongest predictors of common peaks. Compared with strong peaks located in regions containing peaks for multiple transcription factors, weak and isolated peaks are less common between the cell types and are less associated with data that indicate regulatory activity. Conclusions Together, the results suggest that experimental noise is prevalent among weak peaks, whereas strong and clustered peaks represent high-confidence binding events that often occur in other cellular contexts. Nevertheless, 30-40% of the strongest and most clustered peaks show context-dependent regulation. We show that by combining signal intensity with additional data—ranging from context independent information such as binding site conservation and position weight matrix scores to context dependent chromatin structure—we can predict whether a ChIP-seq peak is likely to be present in other cellular contexts.

Chemopreventive and renal protective effects for docosahexaenoic acid (DHA: implications of CRP and lipid peroxides

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Darweish MM

2009-04-01

Full Text Available Abstract Background The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA, claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP, lipid peroxidation (measured as malondialdehyde; MDA and leukocytic count (LC. Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein. Results EAC-bearing mice exhibited markedly elevated LC (2-fold, CRP (11-fold and MDA levels (2.7-fold. DHA (125, 250 mg/kg elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively, as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg. Interestingly, DHA (125 mg/kg markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85 and leukocytosis (r = 0.89, thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold, a rise in serum creatinine/urea levels (2–5-fold after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81, TNF-α r = 0.92 and GSH (r = -0

Basic regulatory principles of Escherichia coli's electron transport chain for varying oxygen conditions

NARCIS (Netherlands)

Henkel, S.G.; Ter Beek, A.S.; Steinsiek, S.; Stagge, S.; Bettenbrock, K.; Teixeira De Mattos, M.J.; Sauter, T.; Sawodny, O.; Ederer, M.

2014-01-01

For adaptation between anaerobic, micro-aerobic and aerobic conditions Escherichia coli's metabolism and in particular its electron transport chain (ETC) is highly regulated. Although it is known that the global transcriptional regulators FNR and ArcA are involved in oxygen response it is unclear

The acute effect of cigarette smoking on the high-sensitivity CRP and fibrinogen biomarkers in chronic obstructive pulmonary disease patients.

Science.gov (United States)

van Dijk, Wouter D; Akkermans, Reinier; Heijdra, Yvonne; Weel, Chris van; Schermer, Tjard R J; Scheepers, Paul T J; Lenders, Jacques W M

2013-04-01

The evidence on the acute effects of smoking on biomarkers is limited. Our aim was to study the acute effect of smoking on disease-related biomarkers. The acute effect of smoking on serum high sensitivity CRP (hs-CRP) and plasma fibrinogen and its association with disease severity was studied by challenging 31 chronic obstructive pulmonary disease patients with cigarette smoking and repeatedly measuring these biomarkers before and after smoking. Fibrinogen and hs-CRP increased directly after smoking by 9.4 mg/dl (95% CI: 4.2-14.5) and 0.13 mg/l (95% CI: 0.03-0.23), respectively. Fibrinogen levels remained elevated after 35 min, whereas hs-CRP normalized. Pearson's correlation coefficient between the hs-CRP change and chronic obstructive pulmonary disease severity was 0.25 (p = 0.06). Fibrinogen and hs-CRP increased directly after smoking in the chronic obstructive pulmonary disease patients. Their association with disease risk and/or progression remains to be demonstrated.

Results of the IAEA CRP on studies of advanced reactor technology options for effective incineration of radioactive waste

International Nuclear Information System (INIS)

Maschek, W.; Stanculescu, A.; ); Gopalakrishnan, V.

2007-01-01

The IAEA has initiated a Coordinated Research Project (CRP) on 'Studies of Advanced Reactor Technology Options for Effective Incineration of Radioactive Waste'. The overall objective of the CRP, performed within the framework of IAEA's Nuclear Power Technology Development Section's Technical Working Group on Fast Reactors (TWG-FR), is to increase the capability of Member States in developing and applying advanced technologies in the area of long-lived radioactive waste utilization and transmutation. More specifically, the final goal of the CRP is to deepen the understanding of the dynamics of transmutation systems, especially systems with high minor actinide content. Currently, 20 institutions from 15 member states and one international organization are participating in this CRP. The current author list comprises the participants of the last CRP Vienna meeting. The CRP concentrates on the assessment of the transient behaviour of various transmutation systems. For a sound assessment of the transient and accident behaviour, neutron kinetics and dynamics methods and codes have to be qualified, especially as the margins for the safety relevant neutronics parameters are generally becoming small in a transmutation system. Hence, the availability of adequate and qualified methods for the analysis of the various systems is an important point of the exercise. A benchmarking effort between the codes and nuclear data used for the analyses has been performed, which will help specifying the range of validity of methods, and also formulate requirements for future theoretical and experimental research. Should transient experiments become available during the course of the CRP, experimental benchmarking work will also be pursued

The effect of captopriland amlodipine on C-reactive protein concentrations in type 2 diabetic hypertensive patients

International Nuclear Information System (INIS)

Mahmood, I.H.

2008-01-01

To compare the effects of the ACE inhibitor captopril with the calcium channel blocker amlodipine on serum CRP concentrations in hypertensive type 2 diabetic patients. This is a case control study conducted in Al-Wafa Diabetic Center in Mosul. Serum CRP concentrations were measured in two groups of hypertensive type 2 diabetic patients before and after drug administration (group 1 on captopril therapy, group two on amlodipine therapy). A significant reduction of serum CRP level was demonstrated after treatment with captopril but not with amlodipine. Mean CRP concentration of the control group was statistically lower than those of captopril and amlodipine groups. The present study showed that hypertensive type 2 diabetic patients are associated with increased level of CRP and therapy with captopril but not amlodipine significantly reduced CRP, suggesting a possible anti-inflammatory action of captopril in addition to its BP lowering effects thus captopril may be regarded as the drug of choice in the treatment of BP in diabetic hypertensive patients. (author)

Serum Pentraxin 3 and hs-CRP Levels in Children with Severe Pulmonary Hypertension

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Cemşit Karakurt

2014-09-01

Full Text Available Background: Pulmonary arterial hypertension secondary to untreated left-to-right shunt defects leads to increased pulmonary blood flow, endothelial dysfunction, increased pulmonary vascular resistance, vascular remodelling, neointimal and plexiform lesions. Some recent studies have shown that inflammation has an important role in the pathophysiology of pulmonary arterial hypertension. Aims: The aim of this study is to evaluate serum pentraxin 3 and high sensitive (hs-C reactive protein (hs-CRP levels in children with severe pulmonary arterial hypertension (PAH secondary to untreated congenital heart defects and evaluate the role of inflammation in pulmonary hypertension. Study Design: Cross sectional study. Methods: After ethics committee approval and receiving consent from parents, there were 31 children were selected for the study with severe PAH, mostly with a left-to-right shunt, who had been assessed by cardiac catheterisation and were taking specific pulmonary vasodilators. The control group consisted of 39 age and gender matched healthy children. After recording data about all the patients including age, gender, weight, haemodynamic studies and vasodilator testing, a physical examination was done for all subjects. Blood was taken from patients and the control group using peripheral veins to analyse serum Pentraxin 3, N-terminal pro-Brain Natriuretic Peptide (NT-ProBNP and hs-CRP levels. Serum Pentraxin-3 levels were measured by enzyme linked immunosorbent assay (ELISA and expressed as ng/mL. Serum hs-CRP levels were measured with an immunonephelometric method and expressed as mg/dL. The serum concentration of NT-proBNP was determined by a chemiluminescent immunumetric assay and expressed as pg/mL. Results: Serum Pentraxin- 3 levels were determined to be 1.28±2.12 (0.12-11.43 in the PAH group (group 1 and 0.40±0.72 (0.07-3.45 in group 2. There was a statistically significant difference between the two groups (p<0.01. Serum hs-CRP levels

Association between Periodontopathogens and CRP Levels in Patients with Periodontitis in Serbia

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Ana Pejcic

2011-03-01

Full Text Available Background and aims. Recent epidemiological studies have shown that individuals with periodontitis have a significantly higher risk of developing coronary heart disease, which might be attributed to the complex microbiota in the dental plaque. Periodontopathogens have been reported as risk factors for cardiovascular disease. This study evaluated association of chronic periodontitis and periodontopathogens with CRP in systemically healthy Serbian adults. Materials and methods. Serum C-reactive protein levels were measured in 24 patients with moderate periodontitis, 26 patients with severe periodontitis, and 25 periodontally healthy subjects. Periodontal health indicators included gingival bleeding on probing and periodontal disease status. Patients with moderate periodontitis had low attachment loss and pocket depths of 5 mm. The control group with healthy gingiva had gingival sulcus of 5 mol/L was greater in the higher clinical AL group compared to the group with less attachment loss. Presence of periodontopathogens was also associated with elevated CRP levels and poor periodontal status. Conclusions. PD and subgingival periodontopathogens are associated with increased CRP levels. These findings suggest that periodontal infection may contribute to systemic inflammatory burden in otherwise healthy individuals.

Early prediction of treatment response by serum CRP levels in patients with advanced esophageal cancer who underwent definitive chemoradiotherapy

International Nuclear Information System (INIS)

Yoneda, Masayuki; Fujiwara, Hitoshi; Okamura, Shinichi

2010-01-01

Serum C reactive protein (CRP) has been shown to be associated with the progression of esophageal cancer. The purpose of this study was to examine the relationship between treatment response and serum CRP levels in time course during definitive chemoradiotherapy (CRT) in terms of early prediction of CRT response by serum CRP. The subjects of this study were 36 patients with cT3/cT4 esophageal squamous cell carcinoma who underwent definitive CRT in our hospital. Serum CRP levels during definitive CRT (pretreatment, 1W, 2W and 3W after CRT initiation) were compared between CR and non-CR group. In addition, partition model was constructed to discriminate CR with non-CR and the prediction accuracy was evaluated. The patients were consisted of 28 males and 8 females. At pretreatment diagnosis, tumors were categorized as T3 (n=21) and T4 (n=15). Thirty four patients received FP-based chemotherapy and 2 patients received docetaxel-based chemotherapy. Treatment responses were categorized as CR (n=8), partial response (PR) (n=14), no change (NC) (n=2) and progressive disease (PD) (n=12). Serum CRP levels at the time of 2W after CRT initiation (CRT2W) in CR group were low compared to those in non-CR group (p=0.071). The partition model was constructed based on CRP levels at CRT2W. The prediction accuracies to discriminate CR from non-CR by CRP ≤0.1 were 50%, 82%, and 75% in sensitivity, specificity and accuracy, respectively. Serum CRP is a useful biomarker for an early prediction of CRT response. (author)

Preterm delivery predicted by soluble CD163 and CRP in women with symptoms of preterm delivery

DEFF Research Database (Denmark)

Vogel, Ida; Grove, Jakob; Thorsen, Poul

2005-01-01

: High levels of sCD163 or CRP are associated with an increased risk of preterm delivery in women with symptoms of delivery. Good prediction of preterm delivery before 34 weeks of gestation was obtained by a combination of preterm prelabour rupture of membranes (PPROM), overweight, relaxin, CRP and s...

Diagnostic value of soluble CD163 serum levels in patients suspected of meningitis: comparison with CRP and procalcitonin

DEFF Research Database (Denmark)

Knudsen, Troels Bygum; Larsen, Klaus; Kristiansen, Thomas Birk

2007-01-01

The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected of meningi......The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected...... marker for distinguishing bacterial infection from non-bacterial disease (specificity 0.91; sensitivity 0.47). However, the overall diagnostic accuracy of CRP (AUC =0.91) and PCT (AUC =0.87) were superior (p... infection, the AUC of sCD163 (0.83) did not differ significantly from those of CRP or PCT. All markers had AUCs CRP and PCT had high diagnostic value and were superior as markers of bacterial infection compared to s...

Cooperative DNA binding of heterologous proteins: Evidence for contact between the cyclic AMP receptor protein and RNA polymerase

International Nuclear Information System (INIS)

Ren, Y.L.; Garges, S.; Adhya, S.; Krakow, J.S.

1988-01-01

Four cAMP-independent receptor protein mutants (designated CRP* mutants) isolated previously are able to activate in vivo gene transcription in the absence of cAMP and their activity can be enhanced by cAMP or cGMP. One of the four mutant proteins, CRP*598 (Arg-142 to His, Ala-144 to Thr), has been characterized with regard to its conformational properties and ability to bind to and support abortive initiation from the lac promoter. Binding of wild-type CRP to its site on the lac promoter and activation of abortive initiation by RNA polymerase on this promoter are effected by cAMP but not by cGMP. CRP*598 can activate lacP + -directed abortive initiation in the presence of cAMP and less efficiently in the presence of cGMP or in the absence of cyclic nucleotide. DNase I protection (footprinting) indicates that cAMP-CRP* binds to its site on the lac promoter whereas unliganded CRP* and cGMP-CRP* form a stable complex with the [ 32 P]lacP + fragment only in the presence of RNA polymerase, showing cooperative binding of two heterologous proteins. This cooperative binding provides strong evidence for a contact between CRP and RNA polymerase for activation of transcription. Although cGMP binds to CRP, it cannot replace cAMP in effecting the requisite conformational transition necessary for site-specific promoter binding

The efficacy of radiofrequency ablation in the treatment of pediatric arrhythmia and its effects on serum IL-6 and hs-CRP.

Science.gov (United States)

Li, Chunli; Jia, Libo; Wang, Zhenzhou; Niu, Ling; An, Xinjiang

2017-10-01

The aim of this study was to investigate the efficacy of radiofrequency ablation in the treatment of pediatric arrhythmia and to assess the changes in serum interleukin-6 (IL-6) and hs-CRP levels after treatment. Hundred and six children with tachyarrhythmia who were admitted to Xuzhou Children's Hospital from November, 2014 to December, 2015 were recruited for study. The efficacies of radiofrequency in the treatment of different types of arrhythmia were analyzed. Successful ablation was found in 104 cases (98.11%) and recurrence was found in 7 cases (6.73%). Among 62 cases of atrioventricular reentrant tachycardia (AVRT), successful ablation was found in 60 cases (96.77%) and recurrence was found in 3 cases (4.84%). Among 33 cases of atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation was found in 33 cases (100%) and recurrence was found in 2 cases (6.06%). Among 5 cases of ventricular tachycardia (VT), successful ablation was found in 5 cases (100%) and no recurrence was found. Among 4 cases of atrial tachycardia (AT), successful ablation was found in 4 cases (100%) and recurrence was found in 1 case (25%). Among 2 cases of atrial flutter (AFL), successful ablation was found in both (100%) and recurrence was found in 1 case (50%). After operation, the levels of IL-6 and hs-CRP were increased and were continually increased within 6 h after operation. The levels of IL-6 and hs-CRP at 24 h after operation were reduced but still higher than preoperative levels. The duration of radiofrequency and ablation energy were positively correlated with the levels of IL-6 and hs-CRP, while the number of discharges was not significantly correlated with either. In conclusion, radiofrequency ablation is a safe and effective treatment for pediatric arrhythmia. Postoperative monitoring of IL-6 and hs-CRP levels is conducive to understanding postoperative myocardial injury and inflammatory response.

Clinical significance of determination of changes of serum IGF-II, CRP levels after treatment in pediatric patients with broncho-pneumonia

International Nuclear Information System (INIS)

Chen Chuanbin

2006-01-01

Objective: To investigate the changes of serum insulin-like growth factor-II (IGF-II), CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II levels were measured with RIA and serum CRP levels with immune method both before and after treatment in 33 pediatric patients with bronchopneumonia and 35 controls. Results: Before treatment the serum levels of IGF-II, CRP were significantly higher in the patients than those in controls (P 0.05). Conclusion: Determination of serum IGF-II, CRP levels is clinically useful in the management of pediatric patients with bronchopneumonia. (authors)

Clinical significance of determination of serum hypersensitive C reactive protein (HS-CRP) levels in patients with acute coronary syndrome (ACS)

International Nuclear Information System (INIS)

Zhai Chunxi; Zhang Fengju; Wang Kejun

2005-01-01

Objective: To study the relationship between changes in serum HS-CRP levels and the status of atherosclerotic plaques in patients with ACS. Methods: Serum HS-CRP levels were measured in 35 patients with ACS at admission, 1 week and 1 month later as well as in 30 controls without recent infection. Results: HS-CRP levels in patients with ACS were significantly higher than those in the controls (P<0.01). The levels were highest at admission and fell gradually. Conclusion: HS-CRP could be a marker reflecting the status of atherosclerotic plaques in patients with ACS. (authors)

A BMP responsive transcriptional region in the chicken type X collagen gene.

Science.gov (United States)

Volk, S W; Luvalle, P; Leask, T; Leboy, P S

1998-10-01

Bone morphogenetic proteins (BMPs) were originally identified by their ability to induce ectopic bone formation and have been shown to promote both chondrogenesis and chondrocyte hypertrophy. BMPs have recently been found to activate a membrane serine/threonine kinase signaling mechanism in a variety of cell types, but the downstream effectors of BMP signaling in chondrocyte differentiation remain unidentified. We have previously reported that BMP-2 markedly stimulates type X collagen expression in prehypertrophic chick sternal chondrocytes, and that type X collagen mRNA levels in chondrocytes cultured under serum-free (SF) conditions are elevated 3- to 5-fold within 24 h. To better define the molecular mechanisms of induction of chondrocyte hypertrophy by BMPs, we examined the effect of BMPs on type X collagen production by 15-day chick embryo sternal chondrocytes cultured under SF conditions in the presence or absence of 30 ng/ml BMP-2, BMP-4, or BMP-7. Two populations of chondrocytes were used: one representing resting cartilage isolated from the caudal third of the sterna and the second representing prehypertrophic cartilage from the cephalic third of the sterna. BMP-2, BMP-4, and BMP-7 all effectively promoted chondrocyte maturation of cephalic sternal chondrocytes as measured by high levels of alkaline phosphatase, diminished levels of type II collagen, and induction of the hypertrophic chondrocyte-specific marker, type X collagen. To test whether BMP control of type X collagen expression occurs at the transcriptional level, we utilized plasmid constructs containing the chicken collagen X promoter and 5' flanking regions fused to a reporter gene. Constructs were transiently transfected into sternal chondrocytes cultured under SF conditions in the presence or absence of 30 ng/ml BMP-2, BMP-4, or BMP-7. A 533 bp region located 2.4-2.9 kb upstream from the type X collagen transcriptional start site was both necessary and sufficient for strong BMP responsiveness

Non radioactive precursor import into chloroplasts

International Nuclear Information System (INIS)

Lombardo, V.A.; Ottado, J.

2003-01-01

Full text: Eukaryotic cells have a subcellular organization based on organelles. Protein transport to these organelles is quantitatively important because the majority of cellular proteins are codified in nuclear genes and then delivered to their final destination. Most of the chloroplast proteins are translated on cytoplasmic ribosomes as larger precursors with an amino terminal transit peptide that is necessary and sufficient to direct the precursor to the chloroplast. Once inside the organelle the transit peptide is cleaved and the mature protein adopts its folded form. In this work we developed a system for the expression and purification of the pea ferredoxin-NADP + reductase precursor (preFNR) for its import into chloroplasts in non radioactive conditions. We constructed a preFNR fused in its carboxy terminus to a 6 histidines peptide (preFNR-6xHis) that allows its identification using a commercial specific antibody. The construction was expressed, purified, processed and precipitated, rendering a soluble and active preFNR-6xHis that was used in binding and import into chloroplasts experiments. The reisolated chloroplasts were analyzed by SDS-PAGE, electro-blotting and revealed by immuno-detection using either colorimetric or chemiluminescent reactive. We performed also import experiments labeling preFNR and preFNR-6xHis with radioactive methionine as controls. We conclude that preFNR-6xHis is bound and imported into chloroplasts as the wild type preFNR and that both colorimetric or chemiluminescent detection methods are useful to avoid the manipulation of radioactive material. (author)

Association of the C-Reactive Protein Gene (CRP rs1205 C>T Polymorphism with Aortic Valve Calcification in Patients with Aortic Stenosis

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Ewa Wypasek

2015-10-01

Full Text Available Elevation in C-reactive protein (CRP levels have been shown in patients with aortic valve stenosis (AS. Minor allele of the CRP gene (CRP rs1205 C>T polymorphism has been associated with lower plasma CRP concentrations in cohorts of healthy and atherosclerotic patients. Considering the existing similarities between atherosclerosis and AS, we examined the effect of CRP rs1205 C>T polymorphism on the AS severity. Three hundred consecutive Caucasian patients diagnosed with AS were genotyped for the rs1205 C>T polymorphism using the TaqMan assay. Severity of the AS was assessed using transthoracic echocardiography. The degree of calcification was analyzed semi-quantitatively. Carriers of the rs1205 T allele were characterized by elevated serum CRP levels (2.53 (1.51–3.96 vs. 1.68 (0.98–2.90 mg/L, p < 0.001 and a higher proportion of the severe aortic valve calcification (70.4% vs. 55.1%, p = 0.01 compared with major homozygotes. The effect of CRP rs1205 polymorphism on CRP levels is opposite in AS-affected than in unaffected subjects, suggesting existence of a disease-specific molecular regulatory mechanism. Furthermore, rs1205 variant allele predisposes to larger aortic valve calcification, potentially being a novel genetic risk marker of disease progression.

Validity and predictive ability of the juvenile arthritis disease activity score based on CRP versus ESR in a Nordic population-based setting

DEFF Research Database (Denmark)

Nordal, E B; Zak, M; Aalto, K

2012-01-01

To compare the juvenile arthritis disease activity score (JADAS) based on C reactive protein (CRP) (JADAS-CRP) with JADAS based on erythrocyte sedimentation rate (ESR) (JADAS-ESR) and to validate JADAS in a population-based setting.......To compare the juvenile arthritis disease activity score (JADAS) based on C reactive protein (CRP) (JADAS-CRP) with JADAS based on erythrocyte sedimentation rate (ESR) (JADAS-ESR) and to validate JADAS in a population-based setting....

Study of High Sensitive C-Reactive Protein (HS-CRP) After Cardiac Rehabilitation Program in Patients Undergoing Isolated CABG.

Science.gov (United States)

Johari Moghadam, Adel; Azizinejad, Saied

2016-12-01

Although cardiac rehabilitation is known as a tool to reduce the overall risk of cardiovascular complications, its specific role in the reduction of hs-CRP as a marker of inflammation and a proven marker of cardiovascular risk needs further investigation. The present study aims at elucidating the effects of a full course of conventional cardiac rehabilitation program for the period of eight weeks, on the levels of hs-CRP in patients who underwent isolated coronary artery bypass surgery. In this case study, 30 consecutive patients who underwent isolated coronary artery bypass surgery (isolated CABGS), and a full 8-week cardiac rehabilitation program in Tehran Heart Center, were investigated. A group of 30 similar patients, who enrolled in the same period of rehabilitation program but did not participate in practice, was considered as a control group. Serum levels of hs-CRP in both groups were measured retrospectively and in similar days before the start of rehabilitation program and at the end of it (or 8 weeks after initial registration for the control group). Levels of hs-CRP in the rehabilitation group and control group were 5.9 7.7 and 6.3 6.9 respectively before start of the program which was not statistically meaningful ( P -Value = 0.833). However, after the program, level of hs-CRP in the two tested groups changed to 2.3 5.1 and 5.7 6.1 respectively which showed a meaningful correlation ( P -Value = 0.023). These results also showed that decrease in hs-CRP level in the rehabilitated group but not in the control group was statistically meaningful (with P -Value of 0.037 and 0.0723 respectively). In patients undergoing coronary bypass surgery, participating in a full course of cardiac rehabilitation for 8 weeks has resulted in a significant reduction in hs-CRP levels as a marker of cardiovascular risk.

Multi-Marker Strategy in Heart Failure: Combination of ST2 and CRP Predicts Poor Outcome.

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Anne Marie Dupuy

Full Text Available Natriuretic peptides (BNP and NT-proBNP are recognized as gold-standard predictive markers in Heart Failure (HF. However, currently ST2 (member of the interleukin 1 receptor family has emerged as marker of inflammation, fibrosis and cardiac stress. We evaluated ST2 and CRP as prognostic markers in 178 patients with chronic heart failure in comparison with other classical markers such as clinical established parameters but also biological markers: NT-proBNP, hs-cTnT alone or in combination. In multivariate analysis, subsequent addition of ST2 led to age, CRP and ST2 as the only remaining predictors of all-cause mortality (HR 1.03, HR 1.61 and HR 2.75, respectively as well as of cardiovascular mortality (HR 1.00, HR 2.27 and HR 3.78, respectively. The combined increase of ST2 and CRP was significant for predicting worsened outcomes leading to identify a high risk subgroup that individual assessment of either marker. The same analysis was performed with ST2 in combination with Barcelona score. Overall, our findings extend previous data demonstrating that ST2 in combination with CRP as a valuable tool for identifying patients at risk of death.

A transcriptionally active estrogen receptor mutant is a novel type of dominant negative inhibitor of estrogen action.

Science.gov (United States)

McInerney, E M; Ince, B A; Shapiro, D J; Katzenellenbogen, B S

1996-12-01

We have characterized a human estrogen receptor (ER) mutant, V364E, which has a single amino acid substitution in its hormone-binding domain. This ER mutant is fully active or even superactive at saturating levels of estradiol (10(-8) M E2) yet has the capacity to act as a strong dominant negative inhibitor of the wild type ER. In transient transfection assays using ER-negative Chinese hamster ovary (CHO) cells and two different estrogen response element (ERE)-containing promoter reporter genes, V364E treated with 10(-8) M E2 exhibited approximately 250% and 100% of the activity of the wild type ER with these two promoter contexts, respectively. Despite the high activity of V364E when present alone in cells, coexpression of both V364E and wild type ER causes a significant decrease in overall ER-mediated transcriptional activity. On the TATA promoter, where V364E was more inhibitory, estrogen-stimulated activity was reduced by approximately 50% at a 1:1 ratio of mutant to wild type ER expression vector, and at a 10:1 ratio, 75% of ER activity was inhibited. V364E was expressed at lower levels than wild type ER and has a approximately 40-fold lower affinity for E2 compared with wild type ER. In promoter interference assays, V364E exhibited a strict dependence upon E2 for binding to an ERE. Surprisingly, even when V364E was unable to bind to ERE DNA (i.e. either at low E2 concentration or by mutation of its DNA-binding domain), this mutant retained full dominant negative activity. This highly active ER mutant is, thus, able to repress ER-mediated transcription when the mutant and wild type ER are present together in cells, even without DNA binding. Since competition for ERE binding and the formation of inactive heterodimers cannot fully account for the dominant negative activity of V364E, it is probable that altered interactions with proteins important in ER-mediated transcription play a key role in the repression of transcription by V364E. The properties and probable

Clinical significance of measurement of serum hs-CRP, TNF-α and M-CSF levels after treatment in patients with periodontitis

International Nuclear Information System (INIS)

Zhang Yunming

2007-01-01

Objective: To explore the significance of changes of serum hs-CRP, TNF-α and M-CSF levels after treatment in patients with periodontitis. Methods: Serum TNF-α, M-CSF (with RIA), hs-CRP (with immuneturbitity method) levels were determined in 38 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, the serum hs-CRP, TNF-α and M-CSF levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum hs-CRP, TNF-α and M-CSF levels might reflect the progress of disease in patients with periodontitis. (authors)

Analysis of relationship between blood lipid metabolism levels and hs-CRP levels in patients with chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

You Fengjian

2011-01-01

Objective: To study the relationship between blood lipid metabolism levels and hs-CRP levels in the patients with chronic obstructive pulmonary disease. Methods: The levels of plasma blood lipid (with biochemistry) and serum hs-CRP(with high-sensitive immuno turbidimetry) were determined in 96 patients with chronic obstructive pulmonary disease as well as 68 normal controls. Results: The plasma blood lipid levels in 96 patients with chronic obstructive pulmonary disease were significantly lower than those in 68 controls, plasma TC and LDL-C levels were not much difference (P>0.05), plasma HDL-C level was significantly difference (P<0.05), but TG and Lp (a) levels were very prominently difference (P<0.01). And the plasma hs-CRP level was significantly increased also (P<0.01). The close relationship was between blood lipid and hs-CRP levels. Conclusion: The study of relationship between blood lipid levels and hs-CRP levels in patients with COPD was helpful for understand the disease process as well as possible mechanisms. (authors)

IAEA coordinated research project (CRP) on 'Analytical and experimental benchmark analyses of accelerator driven systems'

Energy Technology Data Exchange (ETDEWEB)

Abanades, Alberto [Universidad Politecnica de Madrid (Spain); Aliberti, Gerardo; Gohar, Yousry; Talamo, Alberto [ANL, Argonne (United States); Bornos, Victor; Kiyavitskaya, Anna [Joint Institute of Power Eng. and Nucl. Research ' Sosny' , Minsk (Belarus); Carta, Mario [ENEA, Casaccia (Italy); Janczyszyn, Jerzy [AGH-University of Science and Technology, Krakow (Poland); Maiorino, Jose [IPEN, Sao Paulo (Brazil); Pyeon, Cheolho [Kyoto University (Japan); Stanculescu, Alexander [IAEA, Vienna (Austria); Titarenko, Yury [ITEP, Moscow (Russian Federation); Westmeier, Wolfram [Wolfram Westmeier GmbH, Ebsdorfergrund (Germany)

2008-07-01

In December 2005, the International Atomic Energy Agency (IAEA) has started a Coordinated Research Project (CRP) on 'Analytical and Experimental Benchmark Analyses of Accelerator Driven Systems'. The overall objective of the CRP, performed within the framework of the Technical Working Group on Fast Reactors (TWGFR) of IAEA's Nuclear Energy Department, is to increase the capability of interested Member States in developing and applying advanced reactor technologies in the area of long-lived radioactive waste utilization and transmutation. The specific objective of the CRP is to improve the present understanding of the coupling of an external neutron source (e.g. spallation source) with a multiplicative sub-critical core. The participants are performing computational and experimental benchmark analyses using integrated calculation schemes and simulation methods. The CRP aims at integrating some of the planned experimental demonstration projects of the coupling between a sub-critical core and an external neutron source (e.g. YALINA Booster in Belarus, and Kyoto University's Critical Assembly (KUCA)). The objective of these experimental programs is to validate computational methods, obtain high energy nuclear data, characterize the performance of sub-critical assemblies driven by external sources, and to develop and improve techniques for sub-criticality monitoring. The paper summarizes preliminary results obtained to-date for some of the CRP benchmarks. (authors)

Identification of a novel herpes simplex virus type 1 transcript and protein (AL3) expressed during latency.

Science.gov (United States)

Jaber, Tareq; Henderson, Gail; Li, Sumin; Perng, Guey-Chuen; Carpenter, Dale; Wechsler, Steven L; Jones, Clinton

2009-10-01

The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is abundantly expressed in latently infected sensory neurons. In small animal models of infection, expression of the first 1.5 kb of LAT coding sequences is necessary and sufficient for wild-type reactivation from latency. The ability of LAT to inhibit apoptosis is important for reactivation from latency. Within the first 1.5 kb of LAT coding sequences and LAT promoter sequences, additional transcripts have been identified. For example, the anti-sense to LAT transcript (AL) is expressed in the opposite direction to LAT from the 5' end of LAT and LAT promoter sequences. In addition, the upstream of LAT (UOL) transcript is expressed in the LAT direction from sequences in the LAT promoter. Further examination of the first 1.5 kb of LAT coding sequences revealed two small ORFs that are anti-sense with respect to LAT (AL2 and AL3). A transcript spanning AL3 was detected in productively infected cells, mouse neuroblastoma cells stably expressing LAT and trigeminal ganglia (TG) of latently infected mice. Peptide-specific IgG directed against AL3 specifically recognized a protein migrating near 15 kDa in cells stably transfected with LAT, mouse neuroblastoma cells transfected with a plasmid containing the AL3 ORF and TG of latently infected mice. The inability to detect the AL3 protein during productive infection may have been because the 5' terminus of the AL3 transcript was downstream of the first in-frame methionine of the AL3 ORF during productive infection.

Specificity of the E. coli LysR-type transcriptional regulators.

Directory of Open Access Journals (Sweden)

Gwendowlyn S Knapp

2010-12-01

Full Text Available Families of paralogous oligomeric proteins are common in biology. How the specificity of assembly evolves is a fundamental question of biology. The LysR-Type Transcriptional Regulators (LTTR form perhaps the largest family of transcriptional regulators in bacteria. Because genomes often encode many LTTR family members, it is assumed that many distinct homooligomers are formed simultaneously in the same cell without interfering with each other's activities, suggesting specificity in the interactions. However, this assumption has not been systematically tested.A negative-dominant assay with λcI repressor fusions was used to evaluate the assembly of the LTTRs in E. coli K-12. Thioredoxin (Trx-LTTR fusions were used to challenge the homooligomeric interactions of λcI-LTTR fusions. Eight cI-LTTR fusions were challenged with twenty-eight Trx fusions. LTTRs could be divided into three classes based on their interactions with other LTTRs.Multimerization of LTTRs in E. coli K-12 is mostly specific. However, under the conditions of the assay, many LTTRs interact with more than one noncognate partner. The physiological significance and physical basis for these interactions are not known.

High-sensitive CRP as a predictive marker of long-term outcome in juvenile idiopathic arthritis

DEFF Research Database (Denmark)

Alberdi-Saugstrup, Mikel; Zak, Marek; Nielsen, Susan

2017-01-01

To evaluate whether C-reactive protein (CRP), including variation within the normal range, is predictive of long-term disease outcome in Juvenile Idiopathic Arthritis (JIA). Consecutive patients with newly diagnosed JIA were included prospectively from defined geographic areas of the Nordic...... countries from 1997 to 2000. Inclusion criteria were availability of a baseline serum sample within 12 months after disease onset and 8-year clinical assessment data. Systemic onset JIA was not included. CRP was measured by high-sensitive ELISA (detection limit of 0.2 mg/l). One hundred and thirty...... participants with a median follow-up time of 97 months (range 95–100) were included. At follow-up, 38% of the patients were in remission off medication. Absence of remission was associated with elevated level of CRP at baseline (odds ratio (OR) 1.33, confidence interval (CI) 1.08–1.63, p = 0.007). By applying...

Design principles of a conditional futile cycle exploited for regulation.

Science.gov (United States)

Tolla, Dean A; Kiley, Patricia J; Lomnitz, Jason G; Savageau, Michael A

2015-07-01

In this report, we characterize the design principles of futile cycling in providing rapid adaptation by regulatory proteins that act as environmental sensors. In contrast to the energetically wasteful futile cycles that are avoided in metabolic pathways, here we describe a conditional futile cycle exploited for a regulatory benefit. The FNR (fumarate and nitrate reduction) cycle in Escherichia coli operates under two regimes - a strictly futile cycle in the presence of O2 and as a pathway under anoxic conditions. The computational results presented here use FNR as a model system and provide evidence that cycling of this transcription factor and its labile sensory cofactor between active and inactive states affords rapid signaling and adaptation. We modify a previously developed mechanistic model to examine a family of FNR models each with different cycling speeds but mathematically constrained to be otherwise equivalent, and we identify a trade-off between energy expenditure and response time that can be tuned by evolution to optimize cycling rate of the FNR system for a particular ecological context. Simulations mimicking experiments with proposed double mutant strains offer suggestions for experimentally testing our predictions and identifying potential fitness effects. Our approach provides a computational framework for analyzing other conditional futile cycles, which when placed in their larger biological context may be found to confer advantages to the organism.

Correlation of Serum Levels of Vitronectin, Malondialdehyde and Hs-CRP With Disease Severity in Coronary Artery Disease

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Alireza Yaghoubi

2015-09-01

Conclusion: The association and correlation between VN, MDA and hs-CRP indicate their involvement in the atherosclerosis process that may lead to progression of CAD. Also, these findings suggested that serum levels of VN, MDA and hs-CRP can help as diagnostic and monitoring markers in CAD patients and as markers of disease severity.

Integrated microfluidic system for rapid screening of CRP aptamers utilizing systematic evolution of ligands by exponential enrichment (SELEX).

Science.gov (United States)

Huang, Chao-June; Lin, Hsin-I; Shiesh, Shu-Chu; Lee, Gwo-Bin

2010-03-15

The systematic evolution of ligands by exponential enrichment (SELEX) is an experimental procedure that allows screening of given molecular targets by desired binding affinities from an initial random pool of oligonucleotides and oligomers. The final products of SELEX are usually referred as aptamers, which are recognized as promising molecules for a variety of biomedical applications. However, SELEX is an iterative process requiring multiple rounds of extraction and amplification that demands significant time and labor. Therefore, this study presents a novel, automatic, miniature SELEX platform. As a demonstration, the rapid screening of C-reactive protein (CRP) aptamers was performed. By utilizing microfluidic technologies and magnetic beads conjugated with CRP, aptamers with a high affinity to CRP were extracted from a random single-strand deoxyribonucleic acid (ssDNA) pool. These aptamers were further amplified by an on-chip polymerase chain reaction (PCR) process. After five consecutive extraction and amplification cycles, a specific aptamer with the highest affinity was screened automatically. The screened aptamers were used as a recognition molecule for the detection of CRP. The developed microsystem demonstrated fast screening of CRP aptamers and can be used as a powerful tool to select analyte-specific aptamers for biomedical applications. (c) 2009 Elsevier B.V. All rights reserved.

Concentration-dependent oligomerization of cross-linked complexes between ferredoxin and ferredoxin–NADP+ reductase

International Nuclear Information System (INIS)

Kimata-Ariga, Yoko; Kubota-Kawai, Hisako; Lee, Young-Ho; Muraki, Norifumi; Ikegami, Takahisa; Kurisu, Genji; Hase, Toshiharu

2013-01-01

Highlights: •Cross-linked complexes of ferredoxin (Fd) and Fd–NADP + reductase form oligomers. •In the crystal structures, Fd- and FNR moieties swap across the molecules. •The complexes exhibit concentration-dependent oligomerization at sub-milimolar order. -- Abstract: Ferredoxin–NADP + reductase (FNR) forms a 1:1 complex with ferredoxin (Fd), and catalyzes the electron transfer between Fd and NADP + . In our previous study, we prepared a series of site-specifically cross-linked complexes of Fd and FNR, which showed diverse electron transfer properties. Here, we show that X-ray crystal structures of the two different Fd–FNR cross-linked complexes form oligomers by swapping Fd and FNR moieties across the molecules; one complex is a dimer from, and the other is a successive multimeric form. In order to verify whether these oligomeric structures are formed only in crystal, we investigated the possibility of the oligomerization of these complexes in solution. The mean values of the particle size of these cross-linked complexes were shown to increase with the rise of protein concentration at sub-milimolar order, whereas the size of dissociable wild-type Fd:FNR complex was unchanged as analyzed by dynamic light scattering measurement. The oligomerization products were detected by SDS–PAGE after chemical cross-linking of these complexes at the sub-milimolar concentrations. The extent and concentration-dependent profile of the oligomerizaion were differentiated between the two cross-linked complexes. These results show that these Fd–FNR cross-linked complexes exhibit concentration-dependent oligomerization, possibly through swapping of Fd and FNR moieties also in solution. These findings lead to the possibility that some native multi-domain proteins may present similar phenomenon in vivo

Induction of specific neuron types by overexpression of single transcription factors.

Science.gov (United States)

Teratani-Ota, Yusuke; Yamamizu, Kohei; Piao, Yulan; Sharova, Lioudmila; Amano, Misa; Yu, Hong; Schlessinger, David; Ko, Minoru S H; Sharov, Alexei A

2016-10-01

Specific neuronal types derived from embryonic stem cells (ESCs) can facilitate mechanistic studies and potentially aid in regenerative medicine. Existing induction methods, however, mostly rely on the effects of the combined action of multiple added growth factors, which generally tend to result in mixed populations of neurons. Here, we report that overexpression of specific transcription factors (TFs) in ESCs can rather guide the differentiation of ESCs towards specific neuron lineages. Analysis of data on gene expression changes 2 d after induction of each of 185 TFs implicated candidate TFs for further ESC differentiation studies. Induction of 23 TFs (out of 49 TFs tested) for 6 d facilitated neural differentiation of ESCs as inferred from increased proportion of cells with neural progenitor marker PSA-NCAM. We identified early activation of the Notch signaling pathway as a common feature of most potent inducers of neural differentiation. The majority of neuron-like cells generated by induction of Ascl1, Smad7, Nr2f1, Dlx2, Dlx4, Nr2f2, Barhl2, and Lhx1 were GABA-positive and expressed other markers of GABAergic neurons. In the same way, we identified Lmx1a and Nr4a2 as inducers for neurons bearing dopaminergic markers and Isl1, Fezf2, and St18 for cholinergic motor neurons. A time-course experiment with induction of Ascl1 showed early upregulation of most neural-specific messenger RNA (mRNA) and microRNAs (miRNAs). Sets of Ascl1-induced mRNAs and miRNAs were enriched in Ascl1 targets. In further studies, enrichment of cells obtained with the induction of Ascl1, Smad7, and Nr2f1 using microbeads resulted in essentially pure population of neuron-like cells with expression profiles similar to neural tissues and expressed markers of GABAergic neurons. In summary, this study indicates that induction of transcription factors is a promising approach to generate cultures that show the transcription profiles characteristic of specific neural cell types.

CLINICAL AND MORPHOLOGICAL RESEARCH INTO THE ROLE OF THE TRANSCRIPTION FACTOR NEUROD1 IN VARIOUS TYPES OF PITUITARY ADENOMAS

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O. M. Raspopova

2017-01-01

Full Text Available The role of transcription factors in the pathogenesis of pituitary adenomas is extremely controversial.The aim of the study was to investigate the role of the transcription factor Neuro D1 in various types of pituitary adenomas.Materials and methods. A comparative clinico-morphological study was carried out with immunohistochemical analysis and confocal microscopy of the expression of the transcription factor NeuroD1, six adenohypophysis hormones and Ki-67 in 40 pituitary adenomas and 9 normal pituitary glands.Results. NeuroD1 was expressed in all cases and types of adenomas. The expression level of the transcription factor in adenomas was significantly different from that in the normal pituitary gland (p = 0.006. The average number of cells with expression of NeuroD1 in all tumors was higher than in the normal pituitary gland.Conclusion. NeuroD1 plays one of the key roles in the pathogenesis of pituitary adenomas, regardless of their hormonal status.

Report on the Development of a Close Range Photogrammetry (CRP) Educational Technician Program (Museum and Archive Use).

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Kobelin, Joel

A close range photogrammetry (CRP) technician training program was developed at Miami-Dade Community College and used to teach the technology to 16 students. Although the results of the study show that it is possible to teach CRP in a two-year program, the technology is too new in the United States to support a sustaining educational program. The…

Time dependent transition of the levels of protein-conjugated acrolein (PC-Acro), IL-6 and CRP in plasma during stroke.

Science.gov (United States)

Yoshida, Madoka; Kato, Naoki; Uemura, Takeshi; Mizoi, Mutsumi; Nakamura, Mizuho; Saiki, Ryotaro; Hatano, Keisuke; Sato, Kunitomo; Kakizaki, Shota; Nakamura, Aya; Ishii, Takuya; Terao, Tohru; Murayama, Yuichi; Kashiwagi, Keiko; Igarashi, Kazuei

2017-06-01

Measurement of plasma levels of protein-conjugated acrolein (PC-Acro) together with IL-6 and CRP can be used to identify silent brain infarction (SBI) with high sensitivity and specificity. The aim of this study was to determine how these biomarkers vary during stroke. Levels of PC-Acro, IL-6 and CRP in plasma were measured on day 0, 2, 7 and 14 after the onset of ischemic or hemorrhagic stroke. After the onset of stroke, the level of PC-Acro in plasma was elevated corresponding to the size of stroke. It returned to near control levels by day 2, and remained similar through day 14. The degree of the decrease in PC-Acro on day 2 was greater when the size of brain infarction or hemorrhage was larger. An increase in IL-6 and CRP occurred after the increase in PC-Acro, and it was well correlated with the size of the injury following infarction or hemorrhage. The results suggest that acrolein becomes a trigger for the production of IL-6 and CRP, as previously observed in a mouse model of stroke and in cell culture systems. The increase in IL-6 and CRP was also correlated with poor outcome judging from mRS. The results indicate that the degree of the decrease in PC-Acro and the increase in IL-6 and CRP from day 0 to day 2 was correlated with the size of brain infarction, and the increase in IL-6 and CRP with poor outcome at discharge.

ADA 和 CRP 在结核性脑膜炎和化脓性脑膜炎诊断中的应用%Application of ADA and CRP in the Diagnosis of Tuberculous Meningitis and Purulent Meningitis

Institute of Scientific and Technical Information of China (English)

黄赟; 黄仕辉; 徐荣金

2016-01-01

Objective Through the detection of meningitis patients blood and CSF (cerebrospinal fluid)in Ada (ADA)con-tent detected at the same time,blood CRP (C -reactive protein)content,for differential diagnosis of tuberculous meningitis and purulent meningitis.Method The blood and cerebrospinal fluid of patients with tuberculous meningitis and purulent meningitis in our hospital were detected by ADA and CRP.Meanwhile,The detection results of ADA and CRP were compared and analyzed with the control group of virus and other meningitis.Results By comparing the tuberculous and pyogenic meningitis and the con-trol group,blood and CSF of ADA content was significantly higher in patients with tuberculous meningitis,and the difference was quite obvious.When P <0.05,there was statistic significance;compared with tuberculousmeningitis and matched groups,CPR content in the blood of Purulen meningitis patient was obviously higher and the difference was quite distinctive.When P <0.05, there was statistic significance.Conclusion ADA joint CRP detection of early differential diagnosis of tuberculous and pyogenic meningitis has great value.%目的：通过检测脑膜炎患者血液和 CSF（脑脊液）中的 ADA（腺苷脱氨酶）含量，同时检测患者血液中的CRP（C －反应蛋白）含量，用以鉴别结核性脑膜炎和化脓性脑膜炎。方法：选取儿科结核性脑膜炎和化脓性脑膜炎患者的血及脑脊液作 ADA 和血 CRP 进行生化检测，同时以病毒性及其他脑膜炎作对照组，对 ADA 和 CRP 的检测结果进行比对分析。结果：通过对结核性和化脓性及对照组脑膜炎的比较，结核性脑膜炎患者血和 CSF 中的 ADA 含量明显增高，差异明显，具有统计学意义（P ＜0.05）；CRP 在化脓性脑膜炎患者血液中的含量较结核性和对照组明显增加，差异明显，具有统计学意义（P ＜0.05）。结论：ADA 联合 CRP 检测对早期鉴别诊断结核性与化脓性脑膜炎有较大价值。

Clinical application of combined detection of serum hs-CRP, GMP-140 and cTnI in patients with coronary heart diseases

International Nuclear Information System (INIS)

Qin Jibao; Wu Zhaozeng

2010-01-01

Objective: To explore the clinical significance of changes of serum hs-CRP, GMP-140 and cTnI levels in patients with coronary heart diseases. Methods: Serum GMP-140 (with RIA), cTnI (with ELISA) and hs-CRP (with immuno turbidity method) levels were determined in 91 patients with coronary heart diseases (42 SAP, 34UAP, 15AMI) and 35 controls. Results: Serum hs-CRP, GMP-140, cTnI levels in patients with coronary heart diseases were significantly higher than those in controls (P <0.01). Among the patients with of coronary heart diseases, the magnitude of changes of the levels of serum hs-CRP, GMP-140 and cTnI levels in AMI and UAP groups were significantly larger than those in SAP group (P < 0.05). Serum hs-CRP levels were positively correlated with serum GMP-140 and cTnI levels (r = 0.6214, 0.6023, P < 0.01). Conclusion: Serum hs-CRP, GMP140 and cTnI levels were closely related to the diseases process of coronary heart diseases and were of great clinical importance for assessment of the disease and outcome prediction. (authors)

Is DAS28-CRP with three and four variables interchangeable in individual patients selected for biological treatment in daily clinical practice?

DEFF Research Database (Denmark)

Madsen, Ole Rintek

2011-01-01

DAS28 is a widely used composite score for the assessment of disease activity in patients with rheumatoid arthritis (RA) and is often used as a treatment decision tool in the daily clinic. Different versions of DAS28 are available. DAS28-CRP(3) is calculated based on three variables: swollen...... and tender joint counts and CRP. DAS28-CRP(4) also includes patient global assessment. Thresholds for low and high disease activity are the same for the two scores. Based on the Bland-Altman method, the interchangeability between DAS28-CRP with three and four variables was examined in 319 RA patients...... selected for initiating biological treatment. Data were extracted from the Danish registry for biological treatment in rheumatology (DANBIO). Multiple regression analysis was used to assess the predictability of the DAS28 scores by several measures of disease activity. The overall mean DAS28-CRP was 4...

Arabidopsis Root-Type Ferredoxin:NADP(H) Oxidoreductase 2 is Involved in Detoxification of Nitrite in Roots.

Science.gov (United States)

Hachiya, Takushi; Ueda, Nanae; Kitagawa, Munenori; Hanke, Guy; Suzuki, Akira; Hase, Toshiharu; Sakakibara, Hitoshi

2016-11-01

Ferredoxin:NADP(H) oxidoreductase (FNR) plays a key role in redox metabolism in plastids. Whereas leaf FNR (LFNR) is required for photosynthesis, root FNR (RFNR) is believed to provide electrons to ferredoxin (Fd)-dependent enzymes, including nitrite reductase (NiR) and Fd-glutamine-oxoglutarate aminotransferase (Fd-GOGAT) in non-photosynthetic conditions. In some herbal species, however, most nitrate reductase activity is located in photosynthetic organs, and ammonium in roots is assimilated mainly by Fd-independent NADH-GOGAT. Therefore, RFNR might have a limited impact on N assimilation in roots grown with nitrate or ammonium nitrogen sources. AtRFNR genes are rapidly induced by application of toxic nitrite. Thus, we tested the hypothesis that RFNR could contribute to nitrite reduction in roots by comparing Arabidopsis thaliana seedlings of the wild type with loss-of-function mutants of RFNR2 When these seedlings were grown under nitrate, nitrite or ammonium, only nitrite nutrition caused impaired growth and nitrite accumulation in roots of rfnr2 Supplementation of nitrite with nitrate or ammonium as N sources did not restore the root growth in rfnr2 Also, a scavenger for nitric oxide (NO) could not effectively rescue the growth impairment. Thus, nitrite toxicity, rather than N depletion or nitrite-dependent NO production, probably causes the rfnr2 root growth defect. Our results strongly suggest that RFNR2 has a major role in reduction of toxic nitrite in roots. A specific set of genes related to nitrite reduction and the supply of reducing power responded to nitrite concomitantly, suggesting that the products of these genes act co-operatively with RFNR2 to reduce nitrite in roots. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Clinical significance of changes of serum hs-CRP, IL-6 and TNF-α levels after treatment in patients with polycystic ovary syndrome

International Nuclear Information System (INIS)

Yang Wen; Wang Ying

2010-01-01

Objective: To explore the clinical significance of changes of serum hs-CRP, IL-6 and TNF-α levels in patients with polycystic ovary syndrome. Methods: Serum hs-CRP (with immuno turbidity method), IL-6, TNF-α (with RIA) levels were determined in 31 patients with polycystic ovary syndrome both before and after six, month's treatment as well as 35 controls. Results: Before treatment, the serum hs-CRP, IL-6 and TNF-α levels in the 31 patients with polycystic ovary syndrome were significantly higher than those in controls (P 0.05). Serum hs-CRP levels were positive correlate with serum IL-6, TNF-α levels (r=0.6014, 0.5982, P<0.01). Conclusion: Serum hs-CRP, IL-6 and TNF-α levels were correlated to the development of polycystic ovary syndrome (PCOS). (authors)

Transcriptome Analysis of Polyhydroxybutyrate Cycle Mutants Reveals Discrete Loci Connecting Nitrogen Utilization and Carbon Storage in Sinorhizobium meliloti.

Science.gov (United States)

D'Alessio, Maya; Nordeste, Ricardo; Doxey, Andrew C; Charles, Trevor C

2017-01-01

Polyhydroxybutyrate (PHB) and glycogen polymers are produced by bacteria as carbon storage compounds under unbalanced growth conditions. To gain insights into the transcriptional mechanisms controlling carbon storage in Sinorhizobium meliloti , we investigated the global transcriptomic response to the genetic disruption of key genes in PHB synthesis and degradation and in glycogen synthesis. Under both nitrogen-limited and balanced growth conditions, transcriptomic analysis was performed with genetic mutants deficient in PHB synthesis ( phbA , phbB , phbAB , and phbC ), PHB degradation ( bdhA , phaZ , and acsA2 ), and glycogen synthesis ( glgA1 ). Three distinct genomic regions of the pSymA megaplasmid exhibited altered expression in the wild type and the PHB cycle mutants that was not seen in the glycogen synthesis mutant. An Fnr family transcriptional motif was identified in the upstream regions of a cluster of genes showing similar transcriptional patterns across the mutants. This motif was found at the highest density in the genomic regions with the strongest transcriptional effect, and the presence of this motif upstream of genes in these regions was significantly correlated with decreased transcript abundance. Analysis of the genes in the pSymA regions revealed that they contain a genomic overrepresentation of Fnr family transcription factor-encoding genes. We hypothesize that these loci, containing mostly nitrogen utilization, denitrification, and nitrogen fixation genes, are regulated in response to the intracellular carbon/nitrogen balance. These results indicate a transcriptional regulatory association between intracellular carbon levels (mediated through the functionality of the PHB cycle) and the expression of nitrogen metabolism genes. IMPORTANCE The ability of bacteria to store carbon and energy as intracellular polymers uncouples cell growth and replication from nutrient uptake and provides flexibility in the use of resources as they are available to

Differential 3’ processing of specific transcripts expands regulatory and protein diversity across neuronal cell types

Science.gov (United States)

Jereb, Saša; Hwang, Hun-Way; Van Otterloo, Eric; Govek, Eve-Ellen; Fak, John J; Yuan, Yuan; Hatten, Mary E

2018-01-01

Alternative polyadenylation (APA) regulates mRNA translation, stability, and protein localization. However, it is unclear to what extent APA regulates these processes uniquely in specific cell types. Using a new technique, cTag-PAPERCLIP, we discovered significant differences in APA between the principal types of mouse cerebellar neurons, the Purkinje and granule cells, as well as between proliferating and differentiated granule cells. Transcripts that differed in APA in these comparisons were enriched in key neuronal functions and many differed in coding sequence in addition to 3’UTR length. We characterize Memo1, a transcript that shifted from expressing a short 3’UTR isoform to a longer one during granule cell differentiation. We show that Memo1 regulates granule cell precursor proliferation and that its long 3’UTR isoform is targeted by miR-124, contributing to its downregulation during development. Our findings provide insight into roles for APA in specific cell types and establish a platform for further functional studies. PMID:29578408

Elevated levels of Hs-CRP and IL-6 after delivery are associated with depression during the 6 months post partum.

Science.gov (United States)

Liu, Hao; Zhang, Yang; Gao, Yutao; Zhang, Zhenyu

2016-09-30

The objective of this study is to determine whether inflammatory markers (high-sensitivity C-reactive protein (Hs-CRP) and interleukin (IL)-6) early in the postpartum period contribute to the development of postpartum depression (PPD). From 4 May 2014 to 30 June 2014, all eligible women not on medication for depression giving birth at the Beijing Chao-Yang hospital were consecutively recruited and followed up for 6 months. Depression symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS), and inflammatory biomarkers (Hs-CRP and IL-6) were tested. During the study period, 296 women were enrolled and completed follow-up. In these women, 45 (15.2%) were considered as meeting the criteria for PPD. Serum levels of Hs-CRP and IL-6 in women with PPD were significantly higher than those without PPD (all P<0.0001). Receiver operating characteristics to predict PPD demonstrated areas under the curve of IL-6 of 0.861 (95% confidence interval (CI), 0.801-0.922), which was superior to Hs-CRP (0.837 (95% CI, 0.781-0.894), P<0.01). In multivariate logistic regression analysis, IL-6 and Hs-CRP were independent predictors of PPD. The present study demonstrates a strong relationship between elevated serum Hs-CRP and IL-6 levels at admission and the development of PPD within 6 months. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Association of Irisin and CRP Levels with the Radiographic Severity of Knee Osteoarthritis.

Science.gov (United States)

Mao, Yongtao; Xu, Wei; Xie, Zonggang; Dong, Qirong

2016-02-01

Irisin, a recently identified myokine, is implicated in protecting mice from obesity. This study was designed to examine the relation of irisin levels in serum and synovial fluid (SF) with the radiographic severity of osteoarthritis (OA). Our study included 215 patients with knee OA. Irisin levels in serum and SF were evaluated using an enzyme-linked immunosorbent assay. The progression of OA was assessed using Kellgren-Lawrence grading system. Knee OA patients had lower serum irisin concentrations and increased serum C-reactive protein (CRP) levels compared with healthy controls. There were markedly decreased irisin levels in both the serum and the SF, as well as increased serum CRP levels of knee OA patients with Kellgren and Lawrence (KL) grade 4 compared with patients classified as KL grade 2 and 3. Furthermore, patients with KL grade 3 showed markedly reduced serum and SF levels of irisin, as well as increased serum CRP levels compared with patients classified as KL grade 2. Irisin levels in serum and SF of knee OA patients were negatively correlated with disease severity evaluated by KL grading criteria. Irisin levels in the serum and SF of knee OA patients were negatively correlated with disease severity evaluated by the radiographic KL grading criteria.

The association of C-reactive protein and CRP genotype with coronary heart disease: findings from five studies with 4,610 cases amongst 18,637 participants.

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Debbie A Lawlor

Full Text Available BACKGROUND: It is unclear whether C-reactive protein (CRP is causally related to coronary heart disease (CHD. Genetic variants that are known to be associated with CRP levels can be used to provide causal inference of the effect of CRP on CHD. Our objective was to examine the association between CRP genetic variant +1444C>T (rs1130864 and CHD risk in the largest study to date of this association. METHODS AND RESULTS: We estimated the association of CRP genetic variant +1444C>T (rs1130864 with CRP levels and with CHD in five studies and then pooled these analyses (N = 18,637 participants amongst whom there were 4,610 cases. CRP was associated with potential confounding factors (socioeconomic position, physical activity, smoking and body mass whereas genotype (rs1130864 was not associated with these confounders. The pooled odds ratio of CHD per doubling of circulating CRP level after adjustment for age and sex was 1.13 (95%CI: 1.06, 1.21, and after further adjustment for confounding factors it was 1.07 (95%CI: 1.02, 1.13. Genotype (rs1130864 was associated with circulating CRP; the pooled ratio of geometric means of CRP level among individuals with the TT genotype compared to those with the CT/CC genotype was 1.21 (95%CI: 1.15, 1.28 and the pooled ratio of geometric means of CRP level per additional T allele was 1.14 (95%CI: 1.11, 1.18, with no strong evidence in either analyses of between study heterogeneity (I(2 = 0%, p>0.9 for both analyses. There was no association of genotype (rs1130864 with CHD: pooled odds ratio 1.01 (95%CI: 0.88, 1.16 comparing individuals with TT genotype to those with CT/CC genotype and 0.96 (95%CI: 0.90, 1.03 per additional T allele (I(20.6 for both meta-analyses. An instrumental variables analysis (in which the proportion of CRP levels explained by rs1130864 was related to CHD suggested that circulating CRP was not associated with CHD: the odds ratio for a doubling of CRP level was 1.04 (95%CI: 0.61, 1.80. CONCLUSIONS

Osteoprotegerin improves risk detection by traditional cardiovascular risk factors and hsCRP

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Mogelvang, Rasmus; Haahr-Pedersen, Sune Ammentorp; Bjerre, Mette

2013-01-01

To evaluate the association of plasma osteoprotegerin (OPG) to hospitalisation for ischaemic heart disease (IHD), ischaemic stroke and all-cause mortality, and the effect of combining plasma OPG and high-sensitivity C-reactive protein (hsCRP)....

Clinical significance of determination of serum hypersensitive C-reactive protein (hs-CRP) and E-selectin levels in patients with coronary heart diseases

International Nuclear Information System (INIS)

Yang Chunxiu

2007-01-01

Objective: To investigate the significance of determination of serum contents of hs-CRP and E-Selectin in patients with coronary heart diseases (CHD). Methods: Serum hs-CRP Contents were determined with immuno-turbidity and E-Selectin contents were determined with ELISA in 58 patients with CHD (35SAP, 20UAP, 13AMI) and 35 controls. Results: Serum levels of hs-CRP and E-Selectin in CHD patients were significantly higher than those in controls (P 0.05). Conclusion: The serum levels of hs-CRP and E-Selectin were correlated to the development of CHD, but not to the coronary artery calibers. (authors)

5' diversity of human hepatic PXR (NR1I2) transcripts and identification of the major transcription initiation site.

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Kurose, Kouichi; Koyano, Satoru; Ikeda, Shinobu; Tohkin, Masahiro; Hasegawa, Ryuichi; Sawada, Jun-Ichi

2005-05-01

The human pregnane X receptor (PXR) is a crucial regulator of the genes encoding several major cytochrome P450 enzymes and transporters, such as CYP3A4 and MDR1, but its own transcriptional regulation remains unclear. To elucidate the transcriptional mechanisms of human PXR gene, we first endeavored to identify the transcription initiation site of human PXR using 5'-RACE. Five types of 5'-variable transcripts (a, b, c, d, and e) with common exon 2 sequence were found, and comparison of these sequences with the genomic sequence suggested that their 5' diversity is derived from initiation by alternative promoters and alternative splicing. None of the exons found in our study contain any new in-frame coding regions. Newly identified introns IVS-a and IVS-b were found to have CT-AC splice sites that do not follow the GT-AG rule of conventional donor and acceptor splice sites. Of the five types of 5' variable transcripts identified, RT-PCR showed that type-a was the major transcript type. Four transcription initiation sites (A-D) for type-a transcript were identified by 5'-RACE using GeneRacer RACE Ready cDNA (human liver) constructed by the oligo-capping method. Putative TATA boxes were located approximately 30 bp upstream from the transcriptional start sites of the major transcript (C) and the longest minor transcript (A) expressed in the human liver. These results indicate that the initiation of transcription of human PXR is more complex than previously reported.

High-sensitivity c-reactive protein (hs-CRP) value with 90 days mortality in patients with heart failure

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Nursyamsiah; Hasan, R.

2018-03-01

Hospitalization in patients with chronic heart failure is associated with high rates of mortality and morbidity that during treatment and post-treatment. Despite the various therapies available today, mortality and re-hospitalization rates within 60 to 90 days post-hospitalization are still quite high. This period is known as the vulnerable phase. With the prognostic evaluation tools in patients with heart failure are expected to help identify high-risk individuals, then more rigorous monitoring and interventions can be undertaken. To determine whether hs-CRP have an impact on mortality within 90 days in hospitalized patients with heart failure, an observational cohort study was conducted in 39 patients with heart failure who were hospitalized due to worsening chronic heart failure. Patients were followed for up to 90 days after initial evaluation with the primary endpoint is death. Hs-CRP value >4.25 mg/L we found 70% was dead and hs-CRP value <4.25 mg/L only 6.9% was dead whereas the survival within 90 days. p:0.000.In conclusion, there were differences in hs-CRP values between in patients with heart failure who died and survival within 90 days.

The analysis of high sensitive C-reactive protein and diabetic nephropathy in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Xu Yan

2007-01-01

Objective: To investigate the changes of serum high sensitive C-reactive protein (hs-CRP) in different stages of diabetic nephropathy and their clinical significance. Methods: Serum hs-CRP was measured by enzyme-linked immunosorbent assay (ELISA), U-Alb was measured by radioimmunoassay(RIA). According to their urinary albumin excretion rate(UAER), 102 patients with type 2 diabetes mellitus were divided into three groups: 40 patients with normal UAER, 32 patients with microalbuminuria and 30 patients with clinical proteinuria, and 32 healthy subjects were taken as the controls control. Results: hs-CRP concentrations were significantly higher in patients with type 2 diabetes mellitus than those in healthy controls and increased with increment of UAER and serum creatinine. Conclusions: The level of hs-CRP is correlated with the extend of diabetic nephropathy in patients with type 2 diabetic patients.The concentration of hs-CRP can in some degree serve as a predictor for diabetic rephropathy and its progression. (authors)

Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

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Wang, Xianwei; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L.

2012-01-01

Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22 phox , p47 phox , p67 phox , NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H 2 O 2 . Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac fibroblast growth and collagen

Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription

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Wang, Xianwei, E-mail: XWang2@UAMS.edu; Lu, Jingjun; Khaidakov, Magomed; Mitra, Sona; Ding, Zufeng; Raina, Sameer; Goyal, Tanu; Mehta, Jawahar L., E-mail: MehtaJL@UAMS.edu

2012-03-15

Aspirin (acetyl salicylic acid, ASA) is a common drug used for its analgesic and antipyretic effects. Recent studies show that ASA not only blocks cyclooxygenase, but also inhibits NADPH oxidase and resultant reactive oxygen species (ROS) generation, a pathway that underlies pathogenesis of several ailments, including hypertension and tissue remodeling after injury. In these disease states, angiotensin II (Ang II) activates NADPH oxidase via its type 1 receptor (AT1R) and leads to fibroblast growth and collagen synthesis. In this study, we examined if ASA would inhibit NADPH oxidase activation, upregulation of AT1R transcription, and subsequent collagen generation in mouse cardiac fibroblasts challenged with Ang II. Mouse heart fibroblasts were isolated and treated with Ang II with or without ASA. As expected, Ang II induced AT1R expression, and stimulated cardiac fibroblast growth and collagen synthesis. The AT1R blocker losartan attenuated these effects of Ang II. Similarly to losartan, ASA, and its SA moiety suppressed Ang II-mediated AT1R transcription and fibroblast proliferation as well as expression of collagens and MMPs. ASA also suppressed the expression of NADPH oxidase subunits (p22{sup phox}, p47{sup phox}, p67{sup phox}, NOX2 and NOX4) and ROS generation. ASA did not affect total NF-κB p65, but inhibited its phosphorylation and activation. These observations suggest that ASA inhibits Ang II-induced NADPH oxidase expression, NF-κB activation and AT1R transcription in cardiac fibroblasts, and fibroblast proliferation and collagen expression. The critical role of NADPH oxidase activity in stimulation of AT1R transcription became apparent in experiments where ASA also inhibited AT1R transcription in cardiac fibroblasts challenged with H{sub 2}O{sub 2}. Since SA had similar effect as ASA on AT1R expression, we suggest that ASA's effect is mediated by its SA moiety. -- Highlights: ► Aspirin in therapeutic concentrations decreases mouse cardiac

Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population

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Rajendran Karthick

2012-08-01

Full Text Available Abstract Background Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6 and high sensitivity - C reactive protein (hs-CRP. Results Serum leptin levels were significantly higher in AMI patients when compared to Non-CVD controls. IL-6 and hs-CRP were also elevated in the AMI group and leptin correlated positively with IL-6 and hs-CRP. Incidentally this is the first report from Chennai based population, India. Conclusions The strong correlation between serum levels of leptin and IL-6 implicates an involvement of leptin in the upregulation of inflammatory cytokines during AMI. We hypothesise that the increase in values of IL-6, hs-CRP and their correlation to leptin in AMI patients could be due to participation of leptin in the signaling cascade after myocardial ischemia.

Obesity, Inflammation and Acute Myocardial Infarction - Expression of leptin, IL-6 and high sensitivity-CRP in Chennai based population.

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Rajendran, Karthick; Devarajan, Nalini; Ganesan, Manohar; Ragunathan, Malathi

2012-08-14

Obesity, characterised by increased fat mass and is currently regarded as a pro-inflammatory state and often associated with increased risk of cardiovascular diseases (CVD) including Myocardial infarction. There is an upregulation of inflammatory markers such as interleukin-6, interleukin-6 receptor and acute phase protein CRP in Acute Myocardial Infarction (AMI) patients but the exact mechanism linking obesity and inflammation is not known. It is of our interest to investigate if serum leptin (ob gene product) is associated with AMI and correlated with inflammatory proteins namely Interleukin-6 (IL-6) and high sensitivity - C reactive protein (hs-CRP). Serum leptin levels were significantly higher in AMI patients when compared to Non-CVD controls. IL-6 and hs-CRP were also elevated in the AMI group and leptin correlated positively with IL-6 and hs-CRP. Incidentally this is the first report from Chennai based population, India. The strong correlation between serum levels of leptin and IL-6 implicates an involvement of leptin in the upregulation of inflammatory cytokines during AMI. We hypothesise that the increase in values of IL-6, hs-CRP and their correlation to leptin in AMI patients could be due to participation of leptin in the signaling cascade after myocardial ischemia.

The End of the Line: Can Ferredoxin and Ferredoxin NADP(H) Oxidoreductase Determine the Fate of Photosynthetic Electrons?

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Goss, Tatjana; Hanke, Guy

2014-01-01

At the end of the linear photosynthetic electron transfer (PET) chain, the small soluble protein ferredoxin (Fd) transfers electrons to Fd:NADP(H) oxidoreductase (FNR), which can then reduce NADP+ to support C assimilation. In addition to this linear electron flow (LEF), Fd is also thought to mediate electron flow back to the membrane complexes by different cyclic electron flow (CEF) pathways: either antimycin A sensitive, NAD(P)H complex dependent, or through FNR located at the cytochrome b6f complex. Both Fd and FNR are present in higher plant genomes as multiple gene copies, and it is now known that specific Fd iso-proteins can promote CEF. In addition, FNR iso-proteins vary in their ability to dynamically interact with thylakoid membrane complexes, and it has been suggested that this may also play a role in CEF. We will highlight work on the different Fd-isoproteins and FNR-membrane association found in the bundle sheath (BSC) and mesophyll (MC) cell chloroplasts of the C4 plant maize. These two cell types perform predominantly CEF and LEF, and the properties and activities of Fd and FNR in the BSC and MC are therefore specialized for CEF and LEF respectively. A diversity of Fd isoproteins and dynamic FNR location has also been recorded in C3 plants, algae and cyanobacteria. This indicates that the principles learned from the extreme electron transport situations in the BSC and MC of maize might be usefully applied to understanding the dynamic transition between these states in other systems. PMID:24678667

Glycemic Index and Glycemic Load and Their Association with C-Reactive Protein and Incident Type 2 Diabetes

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Geertruida J. van Woudenbergh

2011-01-01

Full Text Available Objective. To investigate whether the Glycemic Index (GI or Glycemic Load (GL of a diet is associated with C-reactive Protein (CRP and risk of type 2 diabetes in a prospective study. Materials and Methods. Our analysis included 4,366 participants who did not have diabetes at baseline. During follow-up 456 diabetes cases were confirmed. Dietary GI and GL were derived from a food-frequency questionnaire and its association with CRP was examined cross-sectionally using linear regression models. The association of GI and GL with diabetes incidence was examined using Cox proportional hazard models. Results. GL, but not GI, was associated with lnCRP at baseline (bGL=0.11 per 50 units; P=.01. When comparing the highest to the lowest tertile of GI with respect to diabetes incidence, a Relative Risk (RR of 0.95 [95%CI 0.75, 1.21] was found after adjustment for lifestyle and nutritional factors. For GL the RR for diabetes incidence was 1.00 [95%CI 0.74, 1.36]. Additional adjustment for CRP did not change RRs. Conclusion. Since GI was not associated with CRP and risk of type 2 diabetes, it is unlikely that a high GI diet induces the previously shown positive association between CRP and risk of type 2 diabetes by increasing CRP concentrations.

Lifestyle and clinical factors associated with elevated C-reactive protein among newly diagnosed Type 2 diabetes mellitus patients: a cross-sectional study from the nationwide DD2 cohort.

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Svensson, Elisabeth; Mor, Anil; Rungby, Jørgen; Berencsi, Klara; Nielsen, Jens Steen; Stidsen, Jacob V; Friborg, Søren; Brandslund, Ivan; Christiansen, Jens Sandahl; Beck-Nielsen, Henning; Sørensen, Henrik Toft; Thomsen, Reimar W

2014-08-28

We aimed to examine the prevalence of and modifiable factors associated with elevated C-reactive Protein (CRP), a marker of inflammation, in men and women with newly diagnosed Type 2 Diabetes mellitus (DM) in a population-based setting. CRP was measured in 1,037 patients (57% male) with newly diagnosed Type 2 DM included in the prospective nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) project. We assessed the prevalence of elevated CRP and calculated relative risks (RR) examining the association of CRP with lifestyle and clinical factors by Poisson regression, stratified by gender. We used linear regression to examine the association of CRP with other biomarkers. The median CRP value was 2.1 mg/L (interquartile range, 1.0 - 4.8 mg/L). In total, 405 out of the 1,037 Type 2 DM patients (40%) had elevated CRP levels (>3.0 mg/L). More women (46%) than men (34%) had elevated CRP. Among women, a lower risk of elevated CRP was observed in patients receiving statins (adjusted RR (aRR) 0.7 (95% confidence interval (CI) 0.6-0.9)), whereas a higher risk was seen in patients with central obesity (aRR 2.3 (95% CI 1.0-5.3)). For men, CRP was primarily elevated among patients with no regular physical activity (aRR 1.5 (95% CI 1.1-1.9)), previous cardiovascular disease (aRR1.5 (95% CI 1.2-1.9) and other comorbidity. For both genders, elevated CRP was 1.4-fold increased in those with weight gain >30 kg since age 20 years. Sensitivity analyses showed consistent results with the full analysis. The linear regression analysis conveyed an association between high CRP and increased fasting blood glucose. Among newly diagnosed Type 2 DM patients, 40% had elevated CRP levels. Important modifiable risk factors for elevated CRP may vary by gender, and include low physical activity for men and central obesity and absence of statin use for women.

Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms

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Mueller Nancy

2005-10-01

Full Text Available Abstract Background Human T-cell leukemia virus type I (HTLV-I causes adult T-cell leukemia (ATL after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome. Results The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells. Conclusion These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone.

In vitro activation of transcription by the human T-cell leukemia virus type I Tax protein.

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Matthews, M A; Markowitz, R B; Dynan, W S

1992-05-01

The human T-cell leukemia virus type I (HTLV-I) regulatory protein Tax activates transcription of the proviral long terminal repeats and a number of cellular promoters. We have developed an in vitro system to characterize the mechanism by which Tax interacts with the host cell transcription machinery. Tax was purified from cells infected with a baculovirus expression vector. Addition of these Tax preparations to nuclear extracts from uninfected human T lymphocytes activated transcription of the HTLV-I long terminal repeat approximately 10-fold. Transcription-stimulatory activity copurified with the immunoreactive 40-kDa Tax polypeptide on gel filtration chromatography, and, as expected, the effect of recombinant Tax was diminished in HTLV-I-infected T-lymphocyte extracts containing endogenous Tax. Tax-mediated transactivation in vivo has been previously shown to require 21-bp-repeat Tax-responsive elements (TxREs) in the promoter DNA. Stimulation of transcription in vitro was also strongly dependent on these sequences. To investigate the mechanism of Tax transactivation, cellular proteins that bind the 21-bp-repeat TxREs were prepared by DNA affinity chromatography. Recombinant Tax markedly increased the formation of a specific host protein-DNA complex detected in an electrophoretic mobility shift assay. These data suggest that Tax activates transcription through a direct interaction with cellular proteins that bind to the 21-bp-repeat TxREs.

CRP genotype and haplotype associations with serum C-reactive protein level and DAS28 in untreated early rheumatoid arthritis patients

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Ammitzbøll, Christian Gytz; Steffensen, Rudi; Bøgsted, Martin

2014-01-01

investigated: rs11265257, rs1130864, rs1205, rs1800947, rs2808632, rs3093077 and rs876538. The genotype and haplotype associations with CRP and DAS28 levels were evaluated using linear regression analysis adjusted for age, sex and treatment. RESULTS: The minor allele of rs1205 C > T was associated......INTRODUCTION: Single-nucleotide polymorphisms (SNPs) in the CRP gene are implicated in the regulation of the constitutional C-reactive protein (CRP) expression and its response to proinflammatory stimuli. Previous reports suggest that these effects may have an impact on clinical decision...

There Is No Further Gain from Calculating Disease Activity Score in 28 Joints with High Sensitivity Assays of C-Reactive Protein Because of High Intraindividual Variability of CRP

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Jensen Hansen, Inger Marie; Asmussen Andreasen, Rikke; Antonsen, Steen

2016-01-01

Background/Purpose: The threshold for reporting of C-reactive protein (CRP) differs from laboratory to laboratory. Moreover, CRP values are affected by the intra individual biological variability.[1] With respect to disease activity score in 28 joints (DAS28) and Rheumatoid Arthritis (RA), precise...... threshold for reporting CRP is important due to the direct effects of CRP on calculating DAS28, patient classification and subsequent treatment decisions[2] Methods: This study consists of two sections: a theoretical consideration discussing the performance of CRP in calculating DAS28 with regard...... to the biological variation and reporting limit for CRP and a cross sectional study of all RA patients from our department (n=876) applying our theoretical results. In the second section, we calculate DAS28 twice with actual CRP and CRP=9, the latter to elucidate the positive consequences of changing the lower...

Test–retest reliability of the Disease Activity Score 28 CRP (DAS28-CRP), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) in rheumatoid arthritis when based on patient self-assessment of tender and swollen joints

DEFF Research Database (Denmark)

Heegaard, Cecilie; Dreyer, Lene; Egsmose, Charlotte

2013-01-01

and physician-derived scores. Thirty out-clinic RA patients with stable disease were included. A joint count was performed two times 1 week apart by the patient and by an experienced physician. Test-retest reliability was expressed as the least significant difference (LSD), as the LSD in percent of the mean...... score (%LSD) and as intra-individual coefficients of variation (CVi). Mean scores based on physician vs. patient joint counts (visit 1) were: DAS28-CRP(4v) 3.5 ± 1.0 vs. 3.6 ± 1.1 (not significant (NS)), DAS28-CRP(3v) 3.4 ± 0.9 vs. 3.5 ± 0.9 (NS), SDAI 14.2 ± 9.4 vs.14.1 ± 9.4 (NS) and CDAI 13.4 ± 9.......3 vs. 13.3 ± 9.4 (NS). The LSDs (%LSD) for duplicate assessments of patient-derived scores (visit 2 vs. 1) were: DAS28-CRP(4v) 0.8 (23.2), DAS28-CRP(3v) 0.9 (25.2), SDAI 8.3 (59.9) and CDAI 8.4 (63.8). Similar LSDs were found for differences between duplicate assessments of physician-derived scores...

DC-SIGN activation mediates the differential effects of SAP and CRP on the innate immune system and inhibits fibrosis in mice.

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Cox, Nehemiah; Pilling, Darrell; Gomer, Richard H

2015-07-07

Fibrosis is caused by scar tissue formation in internal organs and is associated with 45% of deaths in the United States. Two closely related human serum proteins, serum amyloid P (SAP) and C-reactive protein (CRP), strongly affect fibrosis. In multiple animal models, and in Phase 1 and Phase 2 clinical trials, SAP affects several aspects of the innate immune system to reduce fibrosis, whereas CRP appears to potentiate fibrosis. However, SAP and CRP bind the same Fcγ receptors (FcγR) with similar affinities, and why SAP and CRP have opposing effects is unknown. Here, we report that SAP but not CRP binds the receptor DC-SIGN (SIGN-R1) to affect the innate immune system, and that FcγR are not necessary for SAP function. A polycyclic aminothiazole DC-SIGN ligand and anti-DC-SIGN antibodies mimic SAP effects in vitro. In mice, the aminothiazole reduces neutrophil accumulation in a model of acute lung inflammation and, at 0.001 mg/kg, alleviates pulmonary fibrosis by increasing levels of the immunosuppressant IL-10. DC-SIGN (SIGN-R1) is present on mouse lung epithelial cells, and SAP and the aminothiazole potentiate IL-10 production from these cells. Our data suggest that SAP activates DC-SIGN to regulate the innate immune system differently from CRP, and that DC-SIGN is a target for antifibrotics.

Calculations of IAEA-CRP-6 Benchmark Case 1 through 7 for a TRISO-Coated Fuel Particle

International Nuclear Information System (INIS)

Kim, Young Min; Lee, Y. W.; Chang, J. H.

2005-01-01

IAEA-CRP-6 is a coordinated research program of IAEA on Advances in HTGR fuel technology. The CRP examines aspects of HTGR fuel technology, ranging from design and fabrication to characterization, irradiation testing, performance modeling, as well as licensing and quality control issues. The benchmark section of the program treats simple analytical cases, pyrocarbon layer behavior, single TRISO-coated fuel particle behavior, and benchmark calculations of some irradiation experiments performed and planned. There are totally seventeen benchmark cases in the program. Member countries are participating in the benchmark calculations of the CRP with their own developed fuel performance analysis computer codes. Korea is also taking part in the benchmark calculations using a fuel performance analysis code, COPA (COated PArticle), which is being developed in Korea Atomic Energy Research Institute. The study shows the calculational results of IAEACRP- 6 benchmark cases 1 through 7 which describe the structural behaviors for a single fuel particle

Association of serum hs-CRP and lipids with obesity in school children in a 12-month follow-up study in Japan.

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Nishide, Ritsuko; Ando, Michiko; Funabashi, Hidemitsu; Yoda, Yoshiko; Nakano, Masataka; Shima, Masayuki

2015-03-01

To investigate the association of serum lipids and high-sensitivity C-reactive protein (hs-CRP) with obesity in school children and to explore whether hs-CRP levels could be used to predict the presence or absence of obesity 12 months later. The subjects were school children (6-11 years old) in Japan. Blood sampling and physical measurements were performed in school (2001); low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and hs-CRP levels were measured. Data from children who could be followed 12 months later were analyzed. Subjects weighing 20% or more over his/her standard weight were regarded as obese, and the association of obesity with serum parameters was analyzed. Data from 612 subjects were analyzed (follow-up rate, 75.4%). The mean of each serum parameter was significantly higher (inverse for HDL-C; lower) in obese than that in non-obese children. Logistic regression analysis for obesity at baseline showed that the odds ratio (OR) of hs-CRP was the highest [OR, 2.15; 95% confidence interval (CI), 1.65-2.78 for an interquartile rage (IQR) increase]; the association with triglycerides and LDL-C/HDL-C was significant. At the 12-month follow-up, the OR of high hs-CRP remained the highest of all serum parameters (2.09; 95% CI, 1.63-2.69 for an IQR increase). High levels of triglycerides, LDL-C/HDL-C, and hs-CRP increased the risk of obesity in school children. Hs-CRP is considered to be a better predictor of obesity 12 months later than is LDL-C/HDL-C.

Television imaging system for fast neutron radiography using baby cyclotron

International Nuclear Information System (INIS)

Yoshii, Koji; Miya, Kenzo; Katoh, Norihiko.

1993-01-01

A television imaging system for fast neutron radiography (FNR-TV) developed using the fast neutron source reactor YAYOI was applied to the baby-cyclotron based fast neutron source to get images of thick objects quickly. In the system the same technique as a current television imaging system of thermal neutron radiography was applied, while the luminescent converter was used to detect fast neutrons. Using the CR39 track etch method it took about 7 h to get an image, while the FNR-TV only 20 s enough for taking the same object. However the FNR-TV imaging result of the simulation model of a large explosive device for the space launch vehicle of H-2 type was not so good as the image taken with the CR39 track etch method. The reason was that the luminescence intensity of the FNR-TV converter was a quarter of that in the YAYOI. (author)

Transcriptional activation of the tad type IVb pilus operon by PypB in Yersinia enterocolitica.

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Schilling, Jennifer; Wagner, Karin; Seekircher, Stephanie; Greune, Lilo; Humberg, Verena; Schmidt, M Alexander; Heusipp, Gerhard

2010-07-01

Type IV pili are virulence factors in various bacteria and mediate, among other functions, the colonization of diverse surfaces. Various subclasses of type IV pili have been identified, but information on pilus expression, biogenesis, and the associated phenotypes is sparse for the genus Yersinia. We recently described the identification of PypB as a transcriptional regulator in Yersinia enterocolitica. Here we show that the pypB gene is associated with the tad locus, a genomic island that is widespread among bacterial and archaeal species. The genetic linkage of pypB with the tad locus is conserved throughout the yersiniae but is not found among other bacteria carrying the tad locus. We show that the genes of the tad locus form an operon in Y. enterocolitica that is controlled by PypB and that pypB is part of this operon. The tad genes encode functions necessary for the biogenesis of the Flp subfamily of type IVb pili initially described for Aggregatibacter actinomycetemcomitans to mediate a tight-adherence phenotype. In Y. enterocolitica, the Flp pilin protein shows some peculiarities in its amino acid sequence that imply similarities as well as differences compared to typical motifs found in the Flp subtype of type IVb pili. Flp is expressed and processed after PypB overproduction, resulting in microcolony formation but not in increased adherence to biotic or abiotic surfaces. Our data describe the transcriptional regulation of the tad type IVb pilus operon by PypB in Y. enterocolitica but fail to show most previously described phenotypes associated with this type of pilus in other bacteria.

Fumaric acid esters can block pro-inflammatory actions of human CRP and ameliorate metabolic disturbances in transgenic spontaneously hypertensive rats.

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Jan Šilhavý

Full Text Available Inflammation and oxidative stress have been implicated in the pathogenesis of metabolic disturbances. Esters of fumaric acid, mainly dimethyl fumarate, exhibit immunomodulatory, anti-inflammatory, and anti-oxidative effects. In the current study, we tested the hypothesis that fumaric acid ester (FAE treatment of an animal model of inflammation and metabolic syndrome, the spontaneously hypertensive rat transgenically expressing human C-reactive protein (SHR-CRP, will ameliorate inflammation, oxidative stress, and metabolic disturbances. We studied the effects of FAE treatment by administering Fumaderm, 10 mg/kg body weight for 4 weeks, to male SHR-CRP. Untreated male SHR-CRP rats were used as controls. All rats were fed a high sucrose diet. Compared to untreated controls, rats treated with FAE showed significantly lower levels of endogenous CRP but not transgenic human CRP, and amelioration of inflammation (reduced levels of serum IL6 and TNFα and oxidative stress (reduced levels of lipoperoxidation products in liver, heart, kidney, and plasma. FAE treatment was also associated with lower visceral fat weight and less ectopic fat accumulation in liver and muscle, greater levels of lipolysis, and greater incorporation of glucose into adipose tissue lipids. Analysis of gene expression profiles in the liver with Affymetrix arrays revealed that FAE treatment was associated with differential expression of genes in pathways that involve the regulation of inflammation and oxidative stress. These findings suggest potentially important anti-inflammatory, anti-oxidative, and metabolic effects of FAE in a model of inflammation and metabolic disturbances induced by human CRP.

Post-MI depression and levels of serum IL-6 and CRP in AMI patients

International Nuclear Information System (INIS)

Huang Tiejun

2004-01-01

Objective: To explore the relationship between the presence and severity of post-MI depression and the increased inflammatory activity, as marked by the serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) after myocardial infarction. Methods: Serum IL-6 and CRP levels were measured in 58 AMI patients within 36 hours after onset of event. Depression was evaluated by self-reporting standardized questionnaire, using a validated Chinese version of Hospiatla Anxiety and Depression Scale (HADS)-Depression Subscale (7 items) within 7 days. Demographic and medical data including LVEF, NYHA cardiac function grading, atherosclerosis severity shown from angiography as well as cardiac risk factors were recorded. Results: Serum levels of IL-6 and CRP were higher in depressive AMI patients than those in non-depressive ones (0.93 ± 0.64 vs 0.48 ± 0.37 ng/L, P<0.05 and 0.96 ± 0.41 vs 0.47 ± 0.26 mg/dL, P<0.05). Neither levels of IL-6 nor HADS-D scores were found to be correlated to the severity of atherosclerosis shown in angiography. Conclusion: Presence and severity of post-MI depression is associated with increased activity of inflammation in patients after myocardial infarction. (authors)

Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction.

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Fitch, J M; Gordon, M K; Gibney, E P; Linsenmayer, T F

1995-01-01

The genes for the alpha 1(IX), alpha 1(II), and alpha 2(I) collagen chains can give rise to different isoforms of mRNA, generated by alternative promotor usage [for alpha 1(IX) and alpha 2(I)] or alternative splicing [for alpha 1(II)]. In this study, we employed competitive reverse transcriptase PCR to quantitate the amounts of transcriptional isoforms for these genes in the embryonic avian cornea from its inception (about 3 1/2 days of development) to 11 days. In order to compare values at different time points, the results were normalized to those obtained for the "housekeeping" enzyme, glycerol-3-phosphate dehydrogenase (G3PDH). These values were compared to those obtained from other tissues (anterior optic cup and cartilage) that synthesize different combinations of the collagen isoforms. We found that, in the cornea, transcripts from the upstream promotor of alpha 1(IX) collagen (termed "long IX") were predominant at stage 18-20 (about 3 1/2 days), but then fell rapidly, and remained at a low level. By 5 days (just before stromal swelling) the major mRNA isoform of alpha 1(IX) was from the downstream promoter (termed "short IX"). The relative amount of transcript for the short form of type IX collagen rose to a peak at about 6 days of development, and then declined. Throughout this period, the predominant transcriptional isoform of the collagen type II gene was IIA (i.e., containing the alternatively spliced exon 2). This indicates that the molecules of type II collagen that are assembled into heterotypic fibrils with type I collagen possess, at least transiently, an amino-terminal globular domain similar to that found in collagen types I, III, and V. For type I, the "bone/tendon" mRNA isoform of the alpha 2(I) collagen gene was predominant; transcripts from the downstream promotor were at basal levels. In other tissues expressing collagen types IX and II, long IX was expressed predominantly with the IIA form in the anterior optic cup at stage 22/23; in 14 1

Clinical significance of measurment of changes of serum IGF-I, hs-CRP levels after treatment in patients with hyperthyroidism and hypothyroidism

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Zhu Conggang

2009-01-01

Objective: To explore the clinical significance of changes of serum IGF-I,hs-CRP levels after treatment in patients with hyperthyroidism and hypothyroidism. Methods: Serum IGF-I, hs-CRP(with RIA), and serum hs-CRP with immuno-turbidity methods levels were determined both before and after treatment in 36 cases of hyperthyroidism 30 cases of hypothyroidism as well as 35 controls. Results: Before treatment, the serum IGF-I levels in patients with hyperthyroidism were significantly higher and the levels in patients with hypothyroidism were significantly lower than those in controls (both P<0.01). After treatment for 3 months,the levels were much corrected, but still remained significantly different from those in controls (P<0.05). Before treatment serum hs-CRP levels in both groups of patients were significantly higher than those in controls (P<0.01), but after treatment,the levels were not much different from those in controls. Conclusion: Serum levels of IGF-I and hs-CRP were closely related to the disease process in patients with hyperthyroidism as well as in patients with hypothyroidism, and were much corrected after trentment.(authors)

Calculations of the IAEA-CRP-6 Benchmark Cases by Using the ABAQUS FE Model for a Comparison with the COPA Results

International Nuclear Information System (INIS)

Cho, Moon-Sung; Kim, Y. M.; Lee, Y. W.; Jeong, K. C.; Kim, Y. K.; Oh, S. C.

2006-01-01

The fundamental design for a gas-cooled reactor relies on an understanding of the behavior of a coated particle fuel. KAERI, which has been carrying out the Korean VHTR (Very High Temperature modular gas cooled Reactor) Project since 2004, is developing a fuel performance analysis code for a VHTR named COPA (COated Particle fuel Analysis). COPA predicts temperatures, stresses, a fission gas release and failure probabilities of a coated particle fuel in normal operating conditions. Validation of COPA in the process of its development is realized partly by participating in the benchmark section of the international CRP-6 program led by IAEA which provides comprehensive benchmark problems and analysis results obtained from the CRP-6 member countries. Apart from the validation effort through the CRP-6, a validation of COPA was attempted by comparing its benchmark results with the visco-elastic solutions obtained from the ABAQUS code calculations for the same CRP-6 TRISO coated particle benchmark problems involving creep, swelling, and pressure. The study shows the calculation results of the IAEA-CRP-6 benchmark cases 5 through 7 by using the ABAQUS FE model for a comparison with the COPA results

Uncoupling protein 2 G(-866A polymorphism: a new gene polymorphism associated with C-reactive protein in type 2 diabetic patients C-reactive protein in type 2 diabetic patients

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Cocozza Sergio

2010-10-01

Full Text Available Abstract Background This study evaluated the relationship between the G(-866A polymorphism of the uncoupling protein 2 (UCP2 gene and high-sensitivity C reactive protein (hs-CRP plasma levels in diabetic patients. Methods We studied 383 unrelated people with type 2 diabetes aged 40-70 years. Anthropometry, fasting lipids, glucose, HbA1c, and hs-CRP were measured. Participants were genotyped for the G (-866A polymorphism of the uncoupling protein 2 gene. Results Hs-CRP (mg/L increased progressively across the three genotype groups AA, AG, or GG, being respectively 3.0 ± 3.2, 3.6 ± 5.0, and 4.8 ± 5.3 (p for trend = 0.03. Since hs-CRP values were not significantly different between AA and AG genotype, these two groups were pooled for further analyses. Compared to participants with the AA/AG genotypes, homozygotes for the G allele (GG genotype had significantly higher hs-CRP levels (4.8 ± 5.3 vs 3.5 ± 4.7 mg/L, p = 0.01 and a larger proportion (53.9% vs 46.1%, p = 0.013 of elevated hs-CRP (> 2 mg/L. This was not explained by major confounders such as age, gender, BMI, waist circumference, HbA1c, smoking, or medications use which were comparable in the two genotype groups. Conclusions The study shows for the first time, in type 2 diabetic patients, a significant association of hs-CRP levels with the G(-866A polymorphism of UCP2 beyond the effect of major confounders.

A localized surface plasmon resonance (LSPR) immunosensor for CRP detection using 4-chloro-1-naphtol (4-CN) precipitation

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Ha, Su-Ji; Park, Jin-Ho; Byun, Ju-Young; Ahn, Young-Deok; Kim, Min-Gon

2017-07-01

In this study, C-reactive protein (CRP) was detected by monitoring of LSPR shift promoted by precipitation of 4-chloro-1-naphthol (4-CN). The precipitation occurred by horseradish peroxide (HRP) catalyst which is modified at CRP-detection antibody utilized in sandwich enzyme-linked immunosorbent assay (ELISA) on gold nano bipyramid (GNBP) substrate. Due to 4-CN precipitates which are located nearby the surface of GNBP, local refractive index (RI) and molecular density were greatly increased. This phenomenon eventually induced strong spectral red-shift of absorption band of GNBP. An excellent linear relationship (R2=0.9895) between the LSPR shift and CRP concentration was obtained in the range from 100 pg/mL to 100 ng/mL and limit of detection (LOD) was reached to 87 pg/mL.

Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19-9) in gastric cancer.

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Lukaszewicz-Zając, Marta; Mroczko, Barbara; Gryko, Mariusz; Kędra, Bogusław; Szmitkowski, Maciej

2011-06-01

Gastric cancer (GC) is a second most common cause of cancer-related death and represents an inflammation-driven malignancy. It has been suggested that interleukin 6 (IL-6) and C-reactive protein (CRP) play a potential role in the growth and progression of GC. The aim of the present study was to compare clinical significance of IL-6 and CRP with classic tumor markers-carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in GC patients. The study included 92 patients with GC and 70 healthy subjects. The serum concentrations of IL-6, CEA and CA 19-9 were determined using immunoenzyme assays, whereas CRP using immunoturbidimetric method. We defined the diagnostic criteria and prognostic value for proteins tested. In GC patients, the serum concentrations of all the proteins tested were significantly higher than in healthy subjects. The IL-6, CEA and CA 19-9 levels correlated with nodal metastases, while CRP with tumor stage, gastric wall invasion, presence of nodal and distant metastases. Diagnostic sensitivity of IL-6 was higher (85%) than those of other markers (CRP 66%, CA 19-9 34%, CEA 22%) and increased in combined use with CRP or CEA (88%). The area under ROC curve for IL-6 was larger than those of CRP and classic tumor markers (CEA and CA 19-9). None of the proteins tested was independent prognostic factor for the survival of GC patients. Our findings indicate better usefulness of serum proinflammatory proteins-IL-6 and CRP than classic tumor markers-CEA and CA 19-9 in the diagnosis of GC.

Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity

International Nuclear Information System (INIS)

Liu Wenjin; Sun Maoyun; Jiang Jianhai; Shen Xiaoyun; Sun Qing; Liu Weicheng; Shen Hailian; Gu Jianxin

2004-01-01

The Cyclin D3 protein is a member of the D-type cyclins. Besides serving as cell cycle regulators, D-type cyclins have been reported to be able to interact with several transcription factors and modulate their transcriptional activations. Here we report that human activating transcription factor 5 (hATF5) is a new interacting partner of Cyclin D3. The interaction was confirmed by in vivo coimmunoprecipitation and in vitro binding analysis. Neither interaction between Cyclin D1 and hATF5 nor interaction between Cyclin D2 and hATF5 was observed. Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. Cyclin D3 could potentiate hATF5 transcriptional activity independently of its Cdk4 partner. But Cyclin D1 and Cyclin D2 had no effect on hATF5 transcriptional activity. These data provide a new clue to understand the new role of Cyclin D3 as a transcriptional regulator

Time dependent transition of the levels of protein-conjugated acrolein (PC-Acro, IL-6 and CRP in plasma during stroke

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Madoka Yoshida

2017-06-01

Conclusion: The results indicate that the degree of the decrease in PC-Acro and the increase in IL-6 and CRP from day 0 to day 2 was correlated with the size of brain infarction, and the increase in IL-6 and CRP with poor outcome at discharge.

Agreement between the DAS28-CRP assessed with 3 and 4 variables in patients with rheumatoid arthritis treated with biological agents in the daily clinic

DEFF Research Database (Denmark)

Madsen, Ole Rintek

2013-01-01

The Disease Activity Score-28-C-reactive Protein 4 [DAS28-CRP(4)] composite measure for rheumatoid arthritis (RA) is based on 4 variables: tender and swollen joint counts, CRP, and patient global assessment. DAS28-CRP(3) includes only 3 variables, because patient global assessment has been omitted...

Clinical significance of determination of changes of serum hs-CRP, sICAM-1 and TNF-α levels in patients with gestational diabetes mellitus

International Nuclear Information System (INIS)

Yu Qiuyue

2009-01-01

Objective: To study the relationship between changes of serum sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and soluble intercellular adhesion molecule-1 (sICAM-1) levels and development of the disease in patients with gestational diabetes mellitus(GDM). Methods: Serum levels of TNF-α and sICAM-1(with RIA) and hs-CRP(with immunoturbidimetry) were measured in 30 patients with GDM and 30 normal pregnant women as controls. Results: The serum hs-CRP, sICAM-1 and TNF-α contents in the patients with GDM were all significantly higher than those in normal pregnant women (all P<0.01).The serum hs-CRP levels were mutually positivety correlated with TNF-α and sICAM-1 levels (r=0.6097, 0.7213, all P<0.01). Conclusion: Determination of changes of serum hs-CRP, TNF-α and sICAM-1 levels in patients with gestational diabetes mellitus would be helpful for outcome prediction. (authors)

Metabolic Network Topology Reveals Transcriptional Regulatory Signatures of Type 2 Diabetes

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Zelezniak, Aleksej; Pers, Tune Hannes; Pinho Soares, Simao Pedro

2010-01-01

mechanisms underlying these transcriptional changes and their impact on the cellular metabolic phenotype is a challenging task due to the complexity of transcriptional regulation and the highly interconnected nature of the metabolic network. In this study we integrate skeletal muscle gene expression datasets...... with human metabolic network reconstructions to identify key metabolic regulatory features of T2DM. These features include reporter metabolites—metabolites with significant collective transcriptional response in the associated enzyme-coding genes, and transcription factors with significant enrichment...... factor regulatory network connecting several parts of metabolism. The identified transcription factors include members of the CREB, NRF1 and PPAR family, among others, and represent regulatory targets for further experimental analysis. Overall, our results provide a holistic picture of key metabolic...

The impact of diurnal fasting during Ramadan on the lipid profile, hs-CRP, and serum leptin in stable cardiac patients.

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Khafaji, Hadi Abdul Ridha Hadi; Bener, Abdulbari; Osman, Mohammed; Al Merri, Ajayeb; Al Suwaidi, Jassim

2012-01-01

To study the effect of strict prolonged fasting on lipid profile, serum leptin, and high- sensitivity C-reactive protein (hs-CRP) in patients with different stable cardiac illnesses and look for associated new cardiac events and any correlation between entire variables. A total of 56 patients of different stable cardiac illnesses were followed in our cardiology outpatient for 3 months. Data concerning their ability to fast were collected: New York Heart Association class of congestive cardiac failure, angina class, previous myocardial infarction, previous coronary artery bypass graft, percutaneous coronary intervention, severity of valvular lesion, metallic prosthetic valve, and traditional risk factors (diabetes mellitus, insulin requirement, hypertension, hypercholesterolemia, smoking habit, and obesity). Detailed clinical examination and electrocardiography were performed in all patients in three consecutive visits before, during, and after Ramadan. Echocardiographic and angiographic findings and medication plans were collected from patient records. Lipid profile, serum leptin, and hs-CRP were assessed before, during, and after Ramadan. All patients fasted during Ramadan: 80.4% were male, 67.9% were aged >50 years, 71.4% had no change in their symptoms during fasting while 28.6% felt better. No patient has deteriorated. 91.1% of the patients were compliant with medicine during Ramadan, 73.2% after. 89.3% were compliant with diet during Ramadan with no significant change in body weight in the follow-up period. No cardiac or noncardiac morbidity or mortality was reported. High- density lipoprotein-cholesterol (HDL-C) decreased significantly during compared to before fasting (P = 0.012). Low-density lipoprotein-cholesterol (LDL-C) significantly increased during compared to before fasting (P = 0.022). No statistically significant changes were observed in total cholesterol (TC), triglycerides (TG), serum leptin, or hs-CRP. Significant correlation was observed between

Clinical significance of measurement of changes of serum hs-CRP, IL-6, IL-8 M-CSF levels after treatment in patients with endometriosis

International Nuclear Information System (INIS)

Chen Xiaochao; Zhou Dongxia; Zhang Limin; Liu Hongshu

2008-01-01

Objective: To explore the significance of changes of serum hs-CRP, IL-6, IL-8 and M-CSF levels after treatment in patients with endometriosis. Methods: Serum IL-6, IL-8, M -CSF(with RIA), hs-CRP(with immuneturbidity method)levels were determined in 33 patients with endometriosis both before and after treatment as well as in 35 controls. Results: Before treatment, the serum hs-CRP, IL-6, IL-8 and M-CSF levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum hs-CRP, IL-6, IL-8 and M-CSF levels might reflect the progress of diseases in patients with endometriosis. (authors)

Investigating possible biological targets of Bj-CRP, the first cysteine-rich secretory protein (CRISP) isolated from Bothrops jararaca snake venom.

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Lodovicho, Marina E; Costa, Tássia R; Bernardes, Carolina P; Menaldo, Danilo L; Zoccal, Karina F; Carone, Sante E; Rosa, José C; Pucca, Manuela B; Cerni, Felipe A; Arantes, Eliane C; Tytgat, Jan; Faccioli, Lúcia H; Pereira-Crott, Luciana S; Sampaio, Suely V

2017-01-04

Cysteine-rich secretory proteins (CRISPs) are commonly described as part of the protein content of snake venoms, nevertheless, so far, little is known about their biological targets and functions. Our study describes the isolation and characterization of Bj-CRP, the first CRISP isolated from Bothrops jararaca snake venom, also aiming at the identification of possible targets for its actions. Bj-CRP was purified using three chromatographic steps (Sephacryl S-200, Source 15Q and C18) and showed to be an acidic protein of 24.6kDa with high sequence identity to other snake venom CRISPs. This CRISP was devoid of proteolytic, hemorrhagic or coagulant activities, and it did not affect the currents from 13 voltage-gated potassium channel isoforms. Conversely, Bj-CRP induced inflammatory responses characterized by increase of leukocytes, mainly neutrophils, after 1 and 4h of its injection in the peritoneal cavity of mice, also stimulating the production of IL-6. Bj-CRP also acted on the human complement system, modulating some of the activation pathways and acting directly on important components (C3 and C4), thus inducing the generation of anaphylatoxins (C3a, C4a and C5a). Therefore, our results for Bj-CRP open up prospects for better understanding this class of toxins and its biological actions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Wild type p53 transcriptionally represses the SALL2 transcription factor under genotoxic stress.

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Carlos Farkas

Full Text Available SALL2- a member of the Spalt gene family- is a poorly characterized transcription factor found deregulated in various cancers, which suggests it plays a role in the disease. We previously identified SALL2 as a novel interacting protein of neurotrophin receptors and showed that it plays a role in neuronal function, which does not necessarily explain why or how SALL2 is deregulated in cancer. Previous evidences indicate that SALL2 gene is regulated by the WT1 and AP4 transcription factors. Here, we identified SALL2 as a novel downstream target of the p53 tumor suppressor protein. Bioinformatic analysis of the SALL2 gene revealed several putative p53 half sites along the promoter region. Either overexpression of wild-type p53 or induction of the endogenous p53 by the genotoxic agent doxorubicin repressed SALL2 promoter activity in various cell lines. However R175H, R249S, and R248W p53 mutants, frequently found in the tumors of cancer patients, were unable to repress SALL2 promoter activity, suggesting that p53 specific binding to DNA is important for the regulation of SALL2. Electrophoretic mobility shift assay demonstrated binding of p53 to one of the identified p53 half sites in the Sall2 promoter, and chromatin immunoprecipitation analysis confirmed in vivo interaction of p53 with the promoter region of Sall2 containing this half site. Importantly, by using a p53ER (TAM knockin model expressing a variant of p53 that is completely dependent on 4-hydroxy-tamoxifen for its activity, we show that p53 activation diminished SALL2 RNA and protein levels during genotoxic cellular stress in primary mouse embryo fibroblasts (MEFs and radiosensitive tissues in vivo. Thus, our finding indicates that p53 represses SALL2 expression in a context-specific manner, adding knowledge to the understanding of SALL2 gene regulation, and to a potential mechanism for its deregulation in cancer.

Effects of oxaliplatin, leucovorin and fluorouracil on serum tumor markers, VEGF, CRP and matrix metalloproteinases in patients with advanced esophageal cancer

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Lei Lei

2017-08-01

Full Text Available Objective: To investigate the effects of oxaliplatin, leucovorin and fluorouracil on serum tumor markers, VEGF, CRP and matrix metalloproteinases in patients with advanced esophageal cancer. Methods: From March 2012 to March 2017 a total of 248 patients with advanced esophageal cancer were selected as the study subjects. According to random data table, they were divided into control group (n=123 and observation group (n=125 according to random data table. The control group was treated with cisplatin combined with fluorouracil, leucovorin chemotherapy, and patients in the observation group received oxaliplatin, leucovorin and fluorouracil chemotherapy, all patients were treated for 2 cycles. The changes of serum tumor markers, VEGF, CRP and matrix metalloproteinase levels in the two groups before and after treatment was compared. Results: Before treatment, there was no significant difference of the levels of serum CA125, CA19-9, CEA, VEGF, CRP, MMP-2 and MMP-9 between the control group and the observation group. Compared with the group before treatment, the levels of CA125, CA19-9, CEA, VEGF, CRP, MMP-2 and MMP-9 in the two groups were significantly lower. After treatment, the level of CA125, CA19-9, CEA, VEGF, CRP, MMP-2 and MMP-9 in the observation group was significantly lower than those of the control group. Conclusion: Oxaliplatin, leucovorin and fluorouracil chemotherapy can effectively reduce the levels of serum tumor markers, VEGF, CRP and matrix metalloproteinase in patients with advanced esophageal cancer, it has important clinical value.

Association Between Free Fatty Acid (FFA and Insulin Resistance: The Role of Inflammation (Adiponectin and high sensivity C-reactive Protein/hs-CRP and Stress Oxidative (Superoxide Dismutase/SOD in Obese Non-Diabetic Individual

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Indriyanti Rafi Sukmawati

2009-12-01

Full Text Available BACKGROUND: Obesity is highly related to insulin resistance, therefore, the increased number of obesity is followed by the increased prevalence of type 2 Diabetes Melitus. Obesity is associated with increased of reactive oxygen species (ROS in muscle, liver and endothelial cells. The increase of ROS would lead to insulin resistance (IR and increased pro-inflammatory protein. FFA plays an important role in IR by inhibiting muscle glucose transport and oxidation via effects on serine/threonine phosphorylation of IRS-1. The aim of this study was discover the existence of SOD, hs-CRP and and adiponectin levels towards the occurrence of insulin resistance which was caused by elevated level of FFA and to discover the interaction between SOD, hs-CRP and adiponectin in non diabetic obese adult male. METHODS: This was observational study with cross sectional design. There were 65 obese male non diabetic subjects and 45 non obese male non diabetic subjects who met the criteria. In this study, measurements were done on body mass index (BMI, fasting glucose, insulin, adiponectin, hs-CRP and SOD. Obese was defined as BMI >25 kg/m2, normal weight was defined as BMI 18.5-23 kh/m2 and Insulin Resistance was defined as HOMA-IR >1. RESULTS: This study showed that Hypoadiponectinemia condition, decreased SOD level and high level of hs-CRP is associated with insulin resistance in obese non diabetic subject. Adiponectin and SOD were correlated negatively with insulin resistance in obese non diabetic (Adiponectin, r=-0.455, p<0.001; SOD, r=-0.262, p=0.003, hs-CRP was positively correlated with insulin resistance in obese non diabetic (r=0.592, p<0.001. FFA levels was increased in obese insulin resistance compared with non obese non insulin resistance. The Odds Ratio of Adiponectin, hs-CRP and SOD in this study was analyzed by logistic binary. The OR for SOD 3.6 (p=0.001, hs-CRP 9.1 (p<0.001 and Adiponectin 7.2 (p<0.001. CONCLUSIONS: This study suggested that FFA

Morphological and genetic characterization of group I Clostridium botulinum type B strain 111 and the transcriptional regulator spoIIID gene knockout mutant in sporulation.

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Hosomi, Koji; Kuwana, Ritsuko; Takamatsu, Hiromu; Kohda, Tomoko; Kozaki, Shunji; Mukamoto, Masafumi

2015-06-01

Clostridium botulinum is a heat-resistant spore-forming bacterium that causes the serious paralytic illness botulism. Heat-resistant spores may cause food sanitation hazards and sporulation plays a central role in the survival of C. botulinum. We observed morphological changes and investigated the role of the transcriptional regulator SpoIIID in the sporulation of C. botulinum type B strain 111 in order to elucidate the molecular mechanism in C. botulinum. C. botulinum type B formed heat-resistant spores through successive morphological changes corresponding to those of Bacillus subtilis, a spore-forming model organism. An analysis of the spoIIID gene knockout mutant revealed that the transcriptional regulator SpoIIID contributed to heat-resistant spore formation by C. botulinum type B and activated the transcription of the sigK gene later during sporulation. Transcription of the spoIIID gene, which differed from that in B. subtilis and Clostridium difficile, was observed in the sigE gene knockout mutant of C. botulinum type B. An analysis of the sigF gene knockout mutant showed that the sporulation-specific sigma factor SigF was essential for transcription of the spoIIID gene in C. botulinum type B. These results suggest that the regulation of sporulation in C. botulinum is not similar to that in B. subtilis and other clostridia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Studies on the relationship between plasma CRP and TNF-α, IL-1β levels in aged patients with acute coronary syndrome

International Nuclear Information System (INIS)

Luo Nanping; Wang Xiangang; Hu Chengjin; Wang Ruishan

2002-01-01

Objective: To investigate the relationship between plasma TNF-α, IL-1β and CRP levels in aged patients with coronary heart disease and to define the inflammation marker which might recognize and predict acute coronary syndrome. Methods: Radioimmunoassay was used to detect plasma levels of TNF-α, IL-1β and CRP. Results: Plasma levels of TNF-α and IL-β in patients with acute coronary syndrome (ACS) were significantly higher than those in controls (p<0.05; p<0.01) and stable coronary heart disease (SCHD) (p<0.05; p<0.01). Plasma CRP levels in patients with ACS (7.99 +- 11.9 ml/L) were also significantly higher than those in controls (0.99 +- 1.5 mg/L; p<0.01) and patients with SCHD (2.71 +- 5.45 mg/L; p<0.05). There was positive correlation between CRP level and TNF-α (r=0.0545; p<0.01) as well as IL-β (r=0.31, p<0.05). Conclusion: The abnormal expression of cytokines in aged patients with coronary heart disease was correlative to inflammation marker CRP, which suggested that the abnormal expression to the occurrence of acute coronary syndrome and might serve as a marker of unstable atherosclerosis plaque

Transcription factor 7-like 2 gene links increased in vivo insulin synthesis to type 2 diabetes

NARCIS (Netherlands)

S. Jainandunsing (Sjaam); Koole, H.R. (H. Rita); van Miert, J.N.I. (Joram N.I.); T. Rietveld (Trinet); J.L.D. Wattimena (Josias); E.J.G. Sijbrands (Eric); F.W.M. de Rooij (Felix)

2018-01-01

textabstractTranscription factor 7-like 2 (TCF7L2) is the main susceptibility gene for type 2 diabetes, primarily through impairing the insulin secretion by pancreatic β cells. However, the exact in vivo mechanisms remain poorly understood. We performed a family study and determined if the T risk

Change in levels of C-reactive protein (CRP) and serum cortisol in morbidly obese patients after laparoscopic sleeve gastrectomy.

Science.gov (United States)

Ruiz-Tovar, Jaime; Oller, Inmaculada; Galindo, Isabel; Llavero, Carolina; Arroyo, Antonio; Calero, Alicia; Diez, María; Zubiaga, Lorea; Calpena, Rafael

2013-06-01

C-Reactive protein (CRP) has been associated with the macro- and microvascular effects of hypertension and diabetes mellitus. Referring to serum cortisol, it has been proposed to contribute to the pathogenesis of metabolic syndrome, and it has been demonstrated that weight loss normalizes cortisol levels and improves insulin resistance. The aims of this study were to analyze CRP and cortisol levels pre- and postoperatively in morbidly obese patients undergoing a laparoscopic sleeve gastrectomy and to correlate them with weight loss and parameters associated with cardiovascular risk. A prospective study of all the morbidly obese patients undergoing laparoscopic sleeve gastrectomy as bariatric procedure between October 2007 and May 2011 was performed. A total of 40 patients were included in the study. CRP levels decreased significantly 12 months after surgery (median reduction of 8.9 mg/l; p = 0.001). Serum cortisol levels decreased significantly 6 months after surgery (median reduction of 34.9 μg/dl; p = 0.001). CRP values reached the normal range (cortisol, a significant association was observed with the cardiovascular risk predictor (triglyceride/high-density lipoprotein cholesterol ratio) from the 6th month after surgery onward (Pearson correlation coefficient, 0.559; p = 0.008). CRP levels are increased preoperatively and in the postoperative course up to 1 year after surgery. Serum cortisol levels remain elevated until the 6th month after surgery. From this moment onward, serum cortisol is associated with the cardiovascular risk predictor reflecting the cardiovascular risk decreasement during the weight loss.

Transcriptional regulatory elements in the noncoding region of human papillomavirus type 6

International Nuclear Information System (INIS)

Wu, Tzyy-Choou.

1989-01-01

The structure and function of the transcriptional regulatory region of human papillomavirus type 6 (HPV-6) has been investigated. To investigate tissue specific gene expression, a sensitive method to detect and localize HPV-6 viral DNA, mRNA and protein in plastic-embedded tissue sections of genital and respiratory tract papillomata by using in situ hybridization and immunoperoxidase assays has been developed. This method, using ultrathin sections and strand-specific 3 H labeled riboprobes, offers the advantages of superior morphological preservation and detection of viral genomes at low copy number with good resolution, and the modified immunocytochemistry provides better sensitivity. The results suggest that genital tract epithelium is more permissive for HPV-6 replication than respiratory tract epithelium. To study the tissue tropism of HPV-6 at the level of regulation of viral gene expression, the polymerase chain reaction was used to isolate the noncoding region (NCR) of HPV-6 in independent isolates. Nucleotide sequence analysis of molecularly cloned DNA identified base substitutions, deletions/insertions and tandem duplications. Transcriptional regulatory elements in the NCR were assayed in recombinant plasmids containing the bacterial gene for chloramphenicol acetyl transferase

Coordinated research project (CRP) on studies of advanced reactor technology options for effective incineration of radioactive waste - Scope and objectives

International Nuclear Information System (INIS)

Stanculescu, A.

2002-01-01

The overall objective of the CRP is to perform R and D tasks contributing towards the proof of practicality for long-lived waste transmutation. For a sound assessment of the transient and accident behaviour, the neutron kinetics and dynamics have to be qualified, especially as the margins for the safety relevant neutronics parameters are becoming small in a 'dedicated' transmuter. The CRP will integrate benchmarking of transient/accident simulation codes focussing on the phenomena and effects relevant to various critical and sub-critical systems under severe neutron flux changes and rearrangements. The CRP will investigate future needs both for theoretical means (data, codes) and experimental information related to the various transmutation systems. The final goals of the CRP are to (a) deepen the understanding of the dynamics of transmutation systems, e.g., the accelerator driven system, especially systems with deteriorated safety parameters, (b) qualify the available methods and specify their range of validity, and (c) formulate requirements for future theoretical developments. Should transient experiments be available, the CRP might also pursue experimental benchmarking work. In any case, based on the results, the CRP will conclude on the potential need of transient experiments and make appropriate proposals for experimental programs. The CRP will consider various transmuter and actinides incinerator concepts, from traditional to very advanced, both critical and sub-critical. No optimization will be performed, experience and good engineering judgment is used to define the design parameters of the various concepts. The generic dynamic behavior of the different systems will be assessed and inter-comparisons will be performed. The concepts are derived from those proposed by the participants in this RCM. Later additions might be considered. The studies will include static, kinetics and dynamics calculations. Influence of burnup on transient behavior will be

Deregulation of sucrose-controlled translation of a bZIP-type transcription factor results in sucrose accumulation in leaves.

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Sunil Kumar Thalor

Full Text Available Sucrose is known to repress the translation of Arabidopsis thaliana AtbZIP11 transcript which encodes a protein belonging to the group of S (S--stands for small basic region-leucine zipper (bZIP-type transcription factor. This repression is called sucrose-induced repression of translation (SIRT. It is mediated through the sucrose-controlled upstream open reading frame (SC-uORF found in the AtbZIP11 transcript. The SIRT is reported for 4 other genes belonging to the group of S bZIP in Arabidopsis. Tobacco tbz17 is phylogenetically closely related to AtbZIP11 and carries a putative SC-uORF in its 5'-leader region. Here we demonstrate that tbz17 exhibits SIRT mediated by its SC-uORF in a manner similar to genes belonging to the S bZIP group of the Arabidopsis genus. Furthermore, constitutive transgenic expression of tbz17 lacking its 5'-leader region containing the SC-uORF leads to production of tobacco plants with thicker leaves composed of enlarged cells with 3-4 times higher sucrose content compared to wild type plants. Our finding provides a novel strategy to generate plants with high sucrose content.

Deregulation of sucrose-controlled translation of a bZIP-type transcription factor results in sucrose accumulation in leaves.

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Thalor, Sunil Kumar; Berberich, Thomas; Lee, Sung Shin; Yang, Seung Hwan; Zhu, Xujun; Imai, Ryozo; Takahashi, Yoshihiro; Kusano, Tomonobu

2012-01-01

Sucrose is known to repress the translation of Arabidopsis thaliana AtbZIP11 transcript which encodes a protein belonging to the group of S (S--stands for small) basic region-leucine zipper (bZIP)-type transcription factor. This repression is called sucrose-induced repression of translation (SIRT). It is mediated through the sucrose-controlled upstream open reading frame (SC-uORF) found in the AtbZIP11 transcript. The SIRT is reported for 4 other genes belonging to the group of S bZIP in Arabidopsis. Tobacco tbz17 is phylogenetically closely related to AtbZIP11 and carries a putative SC-uORF in its 5'-leader region. Here we demonstrate that tbz17 exhibits SIRT mediated by its SC-uORF in a manner similar to genes belonging to the S bZIP group of the Arabidopsis genus. Furthermore, constitutive transgenic expression of tbz17 lacking its 5'-leader region containing the SC-uORF leads to production of tobacco plants with thicker leaves composed of enlarged cells with 3-4 times higher sucrose content compared to wild type plants. Our finding provides a novel strategy to generate plants with high sucrose content.

Metagenomic screening for aromatic compound-responsive transcriptional regulators.

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Taku Uchiyama

Full Text Available We applied a metagenomics approach to screen for transcriptional regulators that sense aromatic compounds. The library was constructed by cloning environmental DNA fragments into a promoter-less vector containing green fluorescence protein. Fluorescence-based screening was then performed in the presence of various aromatic compounds. A total of 12 clones were isolated that fluoresced in response to salicylate, 3-methyl catechol, 4-chlorocatechol and chlorohydroquinone. Sequence analysis revealed at least 1 putative transcriptional regulator, excluding 1 clone (CHLO8F. Deletion analysis identified compound-specific transcriptional regulators; namely, 8 LysR-types, 2 two-component-types and 1 AraC-type. Of these, 9 representative clones were selected and their reaction specificities to 18 aromatic compounds were investigated. Overall, our transcriptional regulators were functionally diverse in terms of both specificity and induction rates. LysR- and AraC- type regulators had relatively narrow specificities with high induction rates (5-50 fold, whereas two-component-types had wide specificities with low induction rates (3 fold. Numerous transcriptional regulators have been deposited in sequence databases, but their functions remain largely unknown. Thus, our results add valuable information regarding the sequence-function relationship of transcriptional regulators.

Relationship of obesity with serum concentrations of leptin, CRP and IL-6 in breast cancer survivors

International Nuclear Information System (INIS)

Babaei, Z; Mosapour, A.; Moslemi, D.; Parsian, H.; Pouramir, M.; Khafri, S.

2015-01-01

Introduction: Several mechanisms have been proposed to explain the adverse effect of obesity on quality of life among women with breast cancer, including alteration in some inflammatory markers. The aim of this study was to determine the status of serum levels of leptin, IL-6 and CRP in obese, overweight and normal weight breast cancer survivors in order to determine the relationship between inflammatory markers’ levels and obesity. Materials and methods: This cross-sectional study was done on 75 women with breast cancer, 30 obese, 15 overweight and 30 normal weight patients. Serum leptin, IL-6, CRP, total protein, albumin and lipid profile as well as anthropometric parameters were measured in three groups. Results: Serum leptin levels of obese patients were significantly higher than those of overweight and normal weight patients ( P < 0.05). Higher serum CRP and lower albumin levels were observed in obese patients in comparison with normal weight patients ( P < 0.05). HDL-C level was significantly different between overweight and normal weight patients ( P < 0.05). Significant differences in serum IL-6 levels were not observed between the study groups ( P > 0.05). Moreover, multiple regression analysis showed that leptin was significantly associated with BMI ( P < 0.001), while albumin was negatively correlated with BMI ( P < 0.05). CRP levels were significantly correlated with BMI and waist-to-hip ratio (WHR) ( P < 0.05). Conclusions: In conclusion, high leptin levels and alteration in acute phase proteins in obese patients may exaggerate the inflammation status. As inflammation has the potential to increase the susceptibility of the patients to metastasis development, it is necessary to decline its rate.

Effects of the whole-body cryotherapy on NTproBNP, hsCRP and troponin I in athletes.

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Banfi, Giuseppe; Melegati, Gianluca; Barassi, Alessandra; d'Eril, Gianlodovico Melzi

2009-11-01

Whole-body cryotherapy refers to brief exposure to very cold air for treating symptoms of various illnesses. In sports medicine, whole-body cryotherapy is administered to improve recovery from muscular trauma. As specific studies are lacking, we measured cardiac markers in 10 top-level rugby players of the Italian National team before and after a 1-week course of daily sessions of whole-body cryotherapy. All subjects continued with the same training workload as that of the previous weeks. N-terminal pro B-type natriuretic peptide (NTproBNP) levels increased but remained within the normal range, whilst troponin I (TnI) and high sensitivity C-reactive protein (hsCRP) were unchanged. Whole-body cryotherapy did not impair cardiac function in this sample of elite athletes.

The murine cytomegalovirus M35 protein antagonizes type I IFN induction downstream of pattern recognition receptors by targeting NF-κB mediated transcription.

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Baca Chan

2017-05-01

Full Text Available The type I interferon (IFN response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV that shuts down signaling following pattern recognition receptor (PRR sensing. Screening of an MCMV open reading frame (ORF library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR. Using a series of luciferase-based reporters with specific transcription factor binding sites, we determined that M35 targets NF-κB-, but not IRF-mediated, transcription. Expression of M35 upon retroviral transduction of immortalized bone marrow-derived macrophages (iBMDM led to reduced IFNβ transcription and secretion upon activation of stimulator of IFN genes (STING-dependent signaling. On the other hand, M35 does not antagonize interferon-stimulated gene (ISG 56 promoter induction or ISG transcription upon exogenous stimulation of the type I IFN receptor (IFNAR. M35 is present in the viral particle and, upon MCMV infection of fibroblasts, is immediately shuttled to the nucleus where it exerts its immunomodulatory effects. Deletion of M35 from the MCMV genome and hence from the viral particle resulted in elevated type I IFN transcription and secretion in vitro and in vivo. In the absence of M35, lower viral titers are observed during acute infection of the host, and productive infection in the salivary glands was not detected. In conclusion, the M35 protein is released by MCMV immediately upon infection in order to deftly inhibit the antiviral type I IFN response by targeting NF-κB-mediated transcription. The identification of this novel viral protein reinforces the importance of timely countermeasures in the complex relationship between virus and host.

Insulin resistance in Chinese patients with type 2 diabetes is associated with C-reactive protein independent of abdominal obesity

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Feng Xiaocheng

2010-12-01

Full Text Available Abstract Background There is debate as to whether the association between C-reactive protein (CRP and insulin resistance is independent of body fatness, particularly central obesity. Therefore, the association among CRP, insulin resistance and obesity was analyzed in Chinese patients with type 2 diabetes. Methods The study included 520 Chinese patients diagnosed with type 2 diabetes with CRP levels not exceeding 10 mg/L. The degree of insulin resistance was determined with the homeostasis model assessment of insulin resistance (HOMA-IR. The CRP levels were categorized into quartiles from the lowest to the highest concentrations (Q1-Q4. Results Body mass index (BMI and waist circumference (WC were both higher in Q4, Q3 and Q2 than those in Q1. HOMA-IR was higher in Q2, Q3 and Q4 than that in Q1 (Q1 vs Q4, P Conclusion These findings showed that insulin resistance was associated with CRP levels independent of abdominal obesity in Chinese patients with type 2 diabetes, suggesting that abdominal obesity could only partly explain the link between subclinical inflammation and insulin resistance.

Regulation of cessation of respiration and killing by cyclic 3',5'-adenosine monophosphate and its receptor protein after far-ultraviolet irradiation of Escherichia coli

International Nuclear Information System (INIS)

Swenson, P.A.; Schenley, R.L.; Joshi, J.G.

1978-01-01

When Escherichia coli B/r cultures are irradiated with ultraviolet light (UV) (254 nm), those cells that are killed stop respiring by 60 min after irradiation. Post-UV treatment with cyclic adenosine 3',5'-adenosine monophosphate (cAMP) causes more cells to stop respiring and to die. We have studied these effects at a UV fluence of 52 I/m 2 in a a wild-type E. coli K 12 strain and in mutants defective in cAMP metabolism. Strain CA 8,000 has crp + and cya + genes for the cAMP receptor protein (CRP) (required for transcription of operons regulated by cAMP) and for adenylate cyclase, respectively; CA 7901 is crp - ; and CA 8306 is a cya deletion (Δ). The wild-type culture showed a small transient cessation of respiration, and addition of cAMP caused cessation to be nearly complete. The crp - culture showed no evidence of cessation of respiration, and cAMP had no effect. The Δ cya mutant also showed no cessation of respiration, but cAMP (5 mM) caused as complete inhibition as in the wild type. cAMP caused a 10-fold loss in viability of UV-irradiated wild-type and Δ cya liquid cultures but had no effect on the cpr - culture. Respiration and viability changes were also studied in a double mutant, CA8404 Δ cya crp*, which has an altered CRP that is, with respect to the lac operon, independent of cAMP. The respiration response to UV was similar to that of the wild-type culture, and both respiration and viability of cells in liquid culture were sensitive to cAMP. The survival data, obtained by plating immediately after irradiation, show the wild type, Δ cya strains, and Δ cya crp* to be equally sensitive and the crp - strain to be more resistant. We conclude that cessation of respiration and cell killing after UV irradiation are regulated by cAMP and the CRP. (orig.) [de

DMPD: Type I interferon [corrected] gene induction by the interferon regulatory factorfamily of transcription factors. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 16979567 Type I interferon [corrected] gene induction by the interferon regulatory factorfamily...ng) (.svg) (.html) (.csml) Show Type I interferon [corrected] gene induction by the interferon regulatory factorfamily...orrected] gene induction by the interferon regulatory factorfamily of transcription factors. Authors Honda K

Influence of glucoregulation quality on c-reactive protein, interleukin-6 and tumor necrosis factor-α level in patients with diabetes type 1

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Mitrović Milena

2011-01-01

Full Text Available Background/Aim. Results of studies which have proved an increased inflammatory activity in diabetes type 1, have been published over recent years. One of possible mechanisms that are used to explain chronic inflammation in diabetes is the state of hyperglycemia leading to the enhanced synthesis of glycosylation end products (AGEs which activate macrophages, increase the oxidative stress and affect the synthesis of interleukins (IL-1, IL-6, tumor necrosis factor-α (TNF-α and C-reactive protein (CRP. The aim of the study was to determine the inflammatory markers (CRP, IL-6, TNF-α in patients with diabetes type 1 and to establish their correlation with glucoregulation parameters and other cardiovascular risk factors as well as to compare them with the healthy controls. Methods. The study included 76 patients with diabetes type 1 and 30 healthy controls. We determined values of inflammatory markers (CRP, IL-6, TNF-α and glucoregulation parameters (fasting glucose HbA1c. Results. The values of CRP (p = 0.014, IL-6 (p = 0.020 and TNF-α (p = 0.037 were statistically significantly higher in the diabetic patients than in the healthy controls. There was a positive correlation between CRP with postprandial glycemia (p = 0.004; the multivariate regression analysis revealed a statistically significant correlation between CRP and age (p = 0.001, smoking (p = 0.055, fasting glucose (p = 0.021 and triglycerides (p = 0.048 as well as between IL-6 and LDLcholesterol (p = 0,009. No statistically significant correlations were found between glycosilated hemoglobin (HbA1c and the inflammatory markers (CRP, IL-6 and TNF-α. Conclusion. The patients with type 1 diabetes were found to have a low level of inflammatory activity manifested by the increased values of CRP, IL-6 and TNF-α.

Influence of glucoregulation quality on C-reactive protein, interleukin-6 and tumor necrosis factor-alpha level in patients with diabetes type 1.

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Mitrović, Milena; Ilić, Tatjana; Stokić, Edita; Paro, Jovanka Novaković; Naglić, Dragana Tomić; Bajkin, Ivana; Icin, Tijana

2011-09-01

Results of studies which have proved an increased inflammatory activity in diabetes type 1, have been published over recent years. One of possible mechanisms that are used to explain chronic inflammation in diabetes is the state of hyperglycemia leading to the enhanced synthesis of glycosylation end products (AGEs) which activate macrophages, increase the oxidative stress and affect the synthesis of interleukins (IL-1, IL-6), tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP). The aim of the study was to determine the inflammatory markers (CRP, IL-6, TNF-alpha) in patients with diabetes type 1 and to establish their correlation with glucoregulation parameters and other cardiovascular risk factors as well as to compare them with the healthy controls. The study included 76 patients with diabetes type 1 and 30 healthy controls. We determined values of inflammatory markers (CRP, IL-6, TNF-alpha) and glucoregulation parameters (fasting glucose HbA(1c)). The values of CRP (p = 0.014), IL-6 (p = 0.020) and TNF-alpha (p = 0.037) were statistically significantly higher in the diabetic patients than in the healthy controls. There was a positive correlation between CRP with postprandial glycemia (p = 0.004); the multivariate regression analysis revealed a statistically significant correlation between CRP and age (p = 0.001), smoking (p = 0.055), fasting glucose (p = 0.021) and triglycerides (p = 0.048) as well as between IL-6 and LDL-cholesterol (p = 0.009). No statistically significant correlations were found between glycosilated hemoglobin (HbA(1c)) and the inflammatory markers (CRP, IL-6 and TNF-alpha). The patients with type 1 diabetes were found to have a low level of inflammatory activity manifested by the increased values of CRP, IL-6 and TNF-alpha.

M1 Macrophages but Not M2 Macrophages Are Characterized by Upregulation of CRP Expression via Activation of NFκB: a Possible Role for Ox-LDL in Macrophage Polarization.

Science.gov (United States)

Kaplan, Marielle; Shur, Anna; Tendler, Yvgeny

2018-04-23

Arterial macrophages comprise a heterogeneous population: pro-inflammatory (M1) and anti-inflammatory (M2). Since C-reactive protein (CRP) is produced by macrophages in atherosclerotic lesions, understanding of CRP regulation in macrophages could be crucial to decipher inflammatory patterns in atherogenesis. We aimed to analyze CRP expression in M1/M2 macrophages and to question whether it involves NFκB signaling pathway. Furthermore, we questioned whether oxidative stress affect macrophage phenotype and modulate macrophage CRP expression. M1/M2 macrophage polarization was validated using THP-1 macrophages. CRP mRNA and protein expression were determined using real-time PCR and immunohistochemistry. Involvement of NFκB was determined by nuclear translocation of p50 subunit and the use of NFκB inhibitor. Involvement of oxidative stress in macrophage phenotypes induction was studied using oxidized-LDL (Ox-LDL) and antioxidants. M1 macrophages were characterized by elevated CRP mRNA expression (by 67%), CRP protein levels (by 108%), and upregulation of NFκB activation compared to control, but these features were not shared by M2 macrophages. Macrophages incubation with Ox-LDL led to a moderate M1 phenotype combined with a M2 phenotype, correlated with increased CRP mRNA expression. Antioxidants inhibited by up to 86% IL6 expression but did not significantly affect IL10 secretion. Antioxidants significantly inhibited CRP expression in M1 macrophages, but not in M2 macrophages. Elevated expression of CRP was characteristic of M1 macrophages rather than M2 through NFκB activation. Oxidative stress could be one of the endogenous triggers for macrophage activation to a mixed M1 and M2 phenotype, in association with increased expression of CRP.

CRP-ductin, the mouse homologue of gp-340/deleted in malignant brain tumors 1 (DMBT1), binds gram-positive and gram-negative bacteria and interacts with lung surfactant protein D

DEFF Research Database (Denmark)

Madsen, Jens; Tornøe, Ida; Nielsen, Ole

2003-01-01

CRP-ductin is a protein expressed mainly by mucosal epithelial cells in the mouse. Sequence homologies indicate that CRP-ductin is the mouse homologue of human gp-340, a glycoprotein that agglutinates microorganisms and binds the lung mucosal collectin surfactant protein-D (SP-D). Here we report...... that purified CRP-ductin binds human SP-D in a calcium-dependent manner and that the binding is not inhibited by maltose. The same properties have previously been observed for gp-340 binding of SP-D. CRP-ductin also showed calcium-dependent binding to both gram-positive and -negative bacteria. A polyclonal...... antibody raised against gp-340 reacted specifically with CRP-ductin in Western blots. Immunoreactivity to CRP-ductin was found in the exocrine pancreas, in epithelial cells throughout the gastrointestinal tract and in the parotid ducts. A panel of RNA preparations from mouse tissues was screened for CRP...

Interaction between C/EBPβ and Tax down-regulates human T-cell leukemia virus type I transcription

International Nuclear Information System (INIS)

Hivin, P.; Gaudray, G.; Devaux, C.; Mesnard, J.-M.

2004-01-01

The human T-cell leukemia virus type I (HTLV-I) Tax protein trans-activates viral transcription through three imperfect tandem repeats of a 21-bp sequence called Tax-responsive element (TxRE). Tax regulates transcription via direct interaction with some members of the activating transcription factor/CRE-binding protein (ATF/CREB) family including CREM, CREB, and CREB-2. By interacting with their ZIP domain, Tax stimulates the binding of these cellular factors to the CRE-like sequence present in the TxREs. Recent observations have shown that CCAAT/enhancer binding protein β (C/EBPβ) forms stable complexes on the CRE site in the presence of CREB-2. Given that C/EBPβ has also been found to interact with Tax, we analyzed the effects of C/EBPβ on viral Tax-dependent transcription. We show here that C/EBPβ represses viral transcription and that Tax is no more able to form a stable complex with CREB-2 on the TxRE site in the presence of C/EBPβ. We also analyzed the physical interactions between Tax and C/EBPβ and found that the central region of C/EBPβ, excluding its ZIP domain, is required for direct interaction with Tax. It is the first time that Tax is described to interact with a basic leucine-zipper (bZIP) factor without recognizing its ZIP domain. Although unexpected, this result explains why C/EBPβ would be unable to form a stable complex with Tax on the TxRE site and could then down-regulate viral transcription. Lastly, we found that C/EBPβ was able to inhibit Tax expression in vivo from an infectious HTLV-I molecular clone. In conclusion, we propose that during cell activation events, which stimulate the Tax synthesis, C/EBPβ may down-regulate the level of HTLV-I expression to escape the cytotoxic-T-lymphocyte response

Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia

International Nuclear Information System (INIS)

Wang Guanghui; Chen Chuanbing; Wang Xianwu

2009-01-01

Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 (with RIA) and hs-CRP (with immunoturbidity method) levels were determined in 36 pediatric patients with bronchopneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and hs-CRP levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Determination of serum IGF-II, IL-6, IL-8 and hs-CRP levels in pediatric patients with bronchopneumonia was important for diagnosis and outcome prediction. (authors)

Characterization of herpes simplex virus type 2 latency-associated transcription in human sacral ganglia and in cell culture.

Science.gov (United States)

Croen, K D; Ostrove, J M; Dragovic, L; Straus, S E

1991-01-01

The ability of herpes simplex virus type 2 (HSV-2) to establish latency in and reactivate from sacral dorsal root sensory ganglia is the basis for recurrent genital herpes. The expression of HSV-2 genes in latently infected human sacral ganglia was investigated by in situ hybridization. Hybridizations with a probe from the long repeat region of HSV-2 revealed strong nuclear signals overlying neurons in sacral ganglia from five of nine individuals. The RNA detected overlaps with the transcript for infected cell protein O but in the opposite, or "anti-sense," orientation. These observations mimic those made previously with HSV-1 in human trigeminal ganglia and confirm the recent findings during latency in HSV-2-infected mice and guinea pigs. Northern hybridization of RNA from infected Vero cells showed that an HSV-2 latency-associated transcript was similar in size to the larger (1.85 kb) latency transcript of HSV-1. Thus, HSV-1 and HSV-2 latency in human sensory ganglia are similar, if not identical, in terms of their cellular localization and pattern of transcription.

Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli.

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Pannuri, Archana; Vakulskas, Christopher A; Zere, Tesfalem; McGibbon, Louise C; Edwards, Adrianne N; Georgellis, Dimitris; Babitzke, Paul; Romeo, Tony

2016-11-01

Cyclic AMP (cAMP) and the cAMP receptor protein (cAMP-CRP) and CsrA are the principal regulators of the catabolite repression and carbon storage global regulatory systems, respectively. cAMP-CRP controls the transcription of genes for carbohydrate metabolism and other processes in response to carbon nutritional status, while CsrA binds to diverse mRNAs and regulates translation, RNA stability, and/or transcription elongation. CsrA also binds to the regulatory small RNAs (sRNAs) CsrB and CsrC, which antagonize its activity. The BarA-UvrY two-component signal transduction system (TCS) directly activates csrB and csrC (csrB/C) transcription, while CsrA does so indirectly. We show that cAMP-CRP inhibits csrB/C transcription without negatively regulating phosphorylated UvrY (P-UvrY) or CsrA levels. A crp deletion caused an elevation in CsrB/C levels in the stationary phase of growth and increased the expression of csrB-lacZ and csrC-lacZ transcriptional fusions, although modest stimulation of CsrB/C turnover by the crp deletion partially masked the former effects. DNase I footprinting and other studies demonstrated that cAMP-CRP bound specifically to three sites located upstream from the csrC promoter, two of which overlapped the P-UvrY binding site. These two proteins competed for binding at the overlapping sites. In vitro transcription-translation experiments confirmed direct repression of csrC-lacZ expression by cAMP-CRP. In contrast, cAMP-CRP effects on csrB transcription may be mediated indirectly, as it bound nonspecifically to csrB DNA. In the reciprocal direction, CsrA bound to crp mRNA with high affinity and specificity and yet exhibited only modest, conditional effects on expression. Our findings are incorporated into an emerging model for the response of Csr circuitry to carbon nutritional status. Csr (Rsm) noncoding small RNAs (sRNAs) CsrB and CsrC of Escherichia coli use molecular mimicry to sequester the RNA binding protein CsrA (RsmA) away from lower

Prognostic Impact of Neutrophil/Lymphocyte Ratio, Platelet Count, CRP, and Albumin Levels in Metastatic Colorectal Cancer Patients Treated with FOLFIRI-Bevacizumab.

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Artaç, Mehmet; Uysal, Mükremin; Karaağaç, Mustafa; Korkmaz, Levent; Er, Zehra; Güler, Tunç; Börüban, Melih Cem; Bozcuk, Hakan

2017-06-01

Metastatic colorectal cancer (mCRC) is a lethal disease and fluorouracil-leucovorin-irinotecan (FOLFIRI) plus bevacizumab (bev) is a standard approach. Hence, there is a strong need for identifying new prognostic factors to show the efficacy of FOLFIRI-bev. This is a retrospective study including patients (n = 90) with mCRC from two centers in Turkey. Neutrophil/lymphocyte (N/L) ratio, platelet count, albumin, and C-reactive protein (CRP) were recorded before FOLFIRI-bev therapy. The efficacy of these factors on progression-free survival (PFS) was analyzed with Kaplan Meier and Cox regression analysis. And the cutoff value of N/L ratio was analyzed with ROC analysis. The median age was 56 years (range 21-80). Forty-seven percent of patients with N/L ratio >2.5 showed progressive disease versus 43 % in patients with N/L ratio ratio >2.5 versus 13.5 months for the patients with N/L ratio analysis, high baseline neutrophil count, LDH, N/L ratio, and CRP were all significantly associated with poor prognosis. At multivariate Cox regression analysis, CRP was confirmed to be a better independent prognostic factor. CRP variable was divided into above the upper limit of normal (ULN) and normal value. The median PFSs of the patients with normal and above ULN were 11.3 versus 5.8 months, respectively (p = 0.022). CRP and N/L ratio are potential predictors for advanced mCRC treated with FOLFIRI-bev.

Clinical significance of determination of changes of serum hs-CRP, TNF-α and E2 levels in female children with simple obesity

International Nuclear Information System (INIS)

Xue Jie; Xu Weiqin; Zhou Hong; Liu Hongshu

2008-01-01

Objective: To explore the clinical significance of changes of serum hs-CRP, TNF-α and E 2 levels in female children with simple obesity. Methods: Serum levels of TNF-α, E 2 (with RIA) and hs-CRP (with immunity turbidity) were detected in 34 female children with simple obesity and 35 controls. Results: In the children with simple obesity, the serum hs-CRP, TNF- α and E 2 levels were significantly higher than those in controls (P 2 levels were mutually positively correlated (r=0.6182, 0.5784, P 2 levels is of help for assessment of severity of obesity as well as outcome prediction in female children. (authors)

MrkH, a novel c-di-GMP-dependent transcriptional activator, controls Klebsiella pneumoniae biofilm formation by regulating type 3 fimbriae expression.

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Jonathan J Wilksch

2011-08-01

Full Text Available Klebsiella pneumoniae causes significant morbidity and mortality worldwide, particularly amongst hospitalized individuals. The principle mechanism for pathogenesis in hospital environments involves the formation of biofilms, primarily on implanted medical devices. In this study, we constructed a transposon mutant library in a clinical isolate, K. pneumoniae AJ218, to identify the genes and pathways implicated in biofilm formation. Three mutants severely defective in biofilm formation contained insertions within the mrkABCDF genes encoding the main structural subunit and assembly machinery for type 3 fimbriae. Two other mutants carried insertions within the yfiN and mrkJ genes, which encode GGDEF domain- and EAL domain-containing c-di-GMP turnover enzymes, respectively. The remaining two isolates contained insertions that inactivated the mrkH and mrkI genes, which encode for novel proteins with a c-di-GMP-binding PilZ domain and a LuxR-type transcriptional regulator, respectively. Biochemical and functional assays indicated that the effects of these factors on biofilm formation accompany concomitant changes in type 3 fimbriae expression. We mapped the transcriptional start site of mrkA, demonstrated that MrkH directly activates transcription of the mrkA promoter and showed that MrkH binds strongly to the mrkA regulatory region only in the presence of c-di-GMP. Furthermore, a point mutation in the putative c-di-GMP-binding domain of MrkH completely abolished its function as a transcriptional activator. In vivo analysis of the yfiN and mrkJ genes strongly indicated their c-di-GMP-specific function as diguanylate cyclase and phosphodiesterase, respectively. In addition, in vitro assays showed that purified MrkJ protein has strong c-di-GMP phosphodiesterase activity. These results demonstrate for the first time that c-di-GMP can function as an effector to stimulate the activity of a transcriptional activator, and explain how type 3 fimbriae

Transcriptional expression of type I interferon response genes and stability of housekeeping genes in the human endometrium and endometriosis

DEFF Research Database (Denmark)

Vestergaard, Anna L; Knudsen, Ulla B; Munk, Torben

2011-01-01

Endometriosis is a painful chronic female disease defined by the presence of endometrial tissue implants in ectopic locations. The pathogenesis is much debated, and type I interferons could be involved. The expression of genes of the type I interferon response were profiled by a specific PCR Array...... of RNA obtained from ectopic and eutopic endometrium collected from 9 endometriosis patients and 9 healthy control women. Transcriptional expression levels of selected interferon-regulated and housekeeping genes were investigated by real-time quantitative reverse transcriptase PCR (qRT-PCR). Stably...... expressed housekeeping genes for valid normalization of transcriptional studies of endometrium and endometriosis have not yet been published. Here, seven housekeeping genes were evaluated for stability using the GeNorm and NormFinder software. A normalization factor based on HMBS, TBP, and YWHAZ expression...

Proinsulin, adiponectin and hsCRP in reproductive age women with polycystic ovary syndrome (PCOS)--the effect of metformin treatment.

Science.gov (United States)

Kruszyńska, Aleksandra; Słowińska-Srzednicka, Jadwiga; Jeske, Wojciech; Zgliczyński, Wojciech

2014-01-01

Women with polycystic ovary syndrome (PCOS) often suffer from obesity and insulin resistance. The role of proinsulin, which is known to be an indicator of fertility outcomes in PCOS women, and that of adiponectin, in the pathogenesis of PCOS is not well elucidated. Our objective was to determine proinsulin, adiponectin, hsCRP and other hormonal and metabolic parameters in PCOS women before and after metformin treatment. Two PCOS groups of patients of reproductive age (90 lean and 88 obese or overweight) with two control groups, adjusted for body mass index (BMI), were compared at baseline. 32 PCOS women were studied at baseline, after three and six months of metformin (1,000 mg/day) treatment. Clinical, anthropometric, biochemical and hormonal parameters were assessed. Proinsulin and hsCRP levels were the highest in obese PCOS women and were statistically different than in lean PCOS women (proinsulin: 11.4 v. 6.9 pmol/L; hsCRP 2.46 v. 0.47 mg/L, p treatment only in obese PCOS women. PCOS, when accompanied by obesity, is associated with elevated proinsulin concentrations, which correlates with higher hsCRP and increased FAI. Proinsulin level decreases due to metformin treatment. Our results suggest that obese or overweight PCOS and lean PCOS are characterised by different hormonal and metabolic parameters and have a different response to metformin treatment.

Traffic exposure in a population with high prevalence type 2 diabetes - Do medications influence concentrations of C-reactive protein?

International Nuclear Information System (INIS)

Rioux, Christine L.; Tucker, Katherine L.; Brugge, Doug; Gute, David M.; Mwamburi, Mkaya

2011-01-01

Type 2 Diabetes (T2D) and particulate air pollution are associated with inflammatory dysregulation. We assessed the modifying effects of diabetes medications on the association of C-reactive protein (CRP), a marker of inflammation, and traffic exposure in adults with T2D (n = 379). CRP concentrations were significantly positively associated with residence ≤100 m of a roadway, >100 m and ≤200 m of a roadway and increased traffic density for individuals using insulin. For individuals using oral hypoglycemic medications (OHAs), CRP was significantly negatively associated with residence >100 m - ≤200 m of a roadway and multiple roadway exposure in an interaction model. Among people with diabetes, individuals on insulin appear to be most vulnerable to the effects of traffic exposure. Disease severity among insulin users may promote the pro-inflammatory response to traffic exposure, though diabetes medications may also modify the response. Possible anti-inflammatory effects of OHAs with traffic exposure merit further evaluation. - Highlights: →We examine traffic exposure in a population with high rates of Type 2 Diabetes. →Differences in CRP were evaluated by traffic levels, medication use and type. →Those on insulin had significantly higher CRP with traffic exposure. →Interaction models demonstrated lower CRP with traffic exposure and OHA use. →Diabetes medications may modify the response to traffic exposure. - Among people with diabetes, individuals on insulin appear to be most vulnerable to the effects of traffic exposure. Diabetes medications may modify the response to traffic.

Traffic exposure in a population with high prevalence type 2 diabetes - Do medications influence concentrations of C-reactive protein?

Energy Technology Data Exchange (ETDEWEB)

Rioux, Christine L., E-mail: christine.rioux@tufts.edu [Department of Public Health and Community Medicine, Tufts University, 136 Harrison Avenue, Boston, MA 02111 (United States); Tucker, Katherine L. [Department of Health Science, Northeastern University, Boston, MA (United States); Brugge, Doug [Department of Public Health and Community Medicine, Tufts University, 136 Harrison Avenue, Boston, MA 02111 (United States); Gute, David M. [Department of Civil and Environmental Engineering, Tufts University, Medford, MA (United States); Mwamburi, Mkaya [Department of Public Health and Community Medicine, Tufts University, 136 Harrison Avenue, Boston, MA 02111 (United States)

2011-08-15

Type 2 Diabetes (T2D) and particulate air pollution are associated with inflammatory dysregulation. We assessed the modifying effects of diabetes medications on the association of C-reactive protein (CRP), a marker of inflammation, and traffic exposure in adults with T2D (n = 379). CRP concentrations were significantly positively associated with residence {<=}100 m of a roadway, >100 m and {<=}200 m of a roadway and increased traffic density for individuals using insulin. For individuals using oral hypoglycemic medications (OHAs), CRP was significantly negatively associated with residence >100 m - {<=}200 m of a roadway and multiple roadway exposure in an interaction model. Among people with diabetes, individuals on insulin appear to be most vulnerable to the effects of traffic exposure. Disease severity among insulin users may promote the pro-inflammatory response to traffic exposure, though diabetes medications may also modify the response. Possible anti-inflammatory effects of OHAs with traffic exposure merit further evaluation. - Highlights: >We examine traffic exposure in a population with high rates of Type 2 Diabetes. >Differences in CRP were evaluated by traffic levels, medication use and type. >Those on insulin had significantly higher CRP with traffic exposure. >Interaction models demonstrated lower CRP with traffic exposure and OHA use. >Diabetes medications may modify the response to traffic exposure. - Among people with diabetes, individuals on insulin appear to be most vulnerable to the effects of traffic exposure. Diabetes medications may modify the response to traffic.

Investigating the Effect of Inflammation on Atrial Fibrillation Occurrence by Measuring Highly Sensitive C-reactive Protein (hs-CRP

Directory of Open Access Journals (Sweden)

Mahdi Hassanzadeh Delui

2014-05-01

Full Text Available Introduction: Atrial fibrillation (AF is the most prevalent cardiac arrhythmias that cardiologists and internists encounter. The goal of this article is to clarify an overview of the evidence linking inflammation to AF existence, which may highlight the effect of some pharmacological agents that have genuine potential to reduce the clinical burden of AF by modulating inflammatory pathways. Materials and Methods: In a case-control study, 50 patients with atrial fibrillation (AF with different etiologies and 50 patients with sinus rhythm and similar bases were selected. Sampling for highly sensitive c-reactive (hs-CRP was done on the patients presenting with AF to the Ghaem hospital between October 2006 and June 2007. Results: Mean age of the patients was 62 years with maximum of 90 and minimum of 36 and standard deviation of 13.80. The most frequent age group was 71-80years. Fifty-four percent of patients were male and 46% were female. Mean serum hs-CRP levels in AF patients with hypertension (HTN ,Ischemic heart disease(IHD, Valvular heart disease (VHD, HTN+IHD and hyperthyroidism were 8.10, 9.40, 8.68, 10.16 and 5.98 mg/Lit; respectively. There was significant difference between hs-CRP levels in hypertensive patients in the two groups (P=0.010. Similar results were observed in IHD patients, VHD patients and HTN+IHD patients in two groups (P=0.015, P=0.037, P=0.000. Conclusion: In addition to some risk factors like baseline cardiac diseases, aging, thyrotoxicosis, pulmonary embolism, pneumonia and cardiac surgery, there also appears to be consistent links between hs-CRP, a marker of inflammation, and the pathogenesis of AF. Introduction: Atrial fibrillation (AF is the most prevalent cardiac arrhythmias that cardiologists and internists encounter. The goal of this article is to clarify an overview of the evidence linking inflammation to AF existence, which may highlight the effect of some pharmacological agents that have genuine potential to

Clinical significance of determination of changes in serum hs-CRP, IL-6, IL-10, and IL-18 levels after treatment in patients with acute conjunctivitis

International Nuclear Information System (INIS)

Liu Jun

2007-01-01

Objective: To study the clinical significance of changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels in patients with acute conjunctivitis after treatment. Methods: Serum IL-6, IL-10 (with RIA) hs-CRP (with Immuno-turbidity) and IL-18 (with ELISA) levels were measured in 38 patients with acute conjunctivitis both before and after treatment as well as in 35 controls. Results: The serum hs-CRP, IL-6, IL-10 and IL-18 levels in the patients before treatment were significantly higher than those in the controls (P 0.05). Conclusion: Measurement of the changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels after treatment might be inportant for outcome prediction in patients with acute conjunctivitis. (authors)

Early Transcriptional Responses of Bovine Chorioallantoic Membrane Explants to Wild Type, ΔvirB2 or ΔbtpB Brucella abortus Infection

Science.gov (United States)

Mol, Juliana P. S.; Costa, Erica A.; Carvalho, Alex F.; Sun, Yao-Hui; Tsolis, Reneé M.; Paixão, Tatiane A.; Santos, Renato L.

2014-01-01

The pathogenesis of the Brucella-induced inflammatory response in the bovine placenta is not completely understood. In this study we evaluated the role of the B. abortus Type IV secretion system and the anti-inflammatory factor BtpB in early interactions with bovine placental tissues. Transcription profiles of chorioallantoic membrane (CAM) explants inoculated with wild type (strain 2308), ΔvirB2 or ΔbtpB Brucella abortus were compared by microarray analysis at 4 hours post infection. Transcripts with significant variation (>2 fold change; Pabortus resulted in slightly more genes with decreased than increased transcription levels. Conversely, infection of trophoblastic cells with the ΔvirB2 or the ΔbtpB mutant strains, that lack a functional T4SS or that has impaired inhibition of TLR signaling, respectively, induced more upregulated than downregulated genes. Wild type Brucella abortus impaired transcription of host genes related to immune response when compared to ΔvirB and ΔbtpB mutants. Our findings suggest that proinflammatory genes are negatively modulated in bovine trophoblastic cells at early stages of infection. The virB operon and btpB are directly or indirectly related to modulation of these host genes. These results shed light on the early interactions between B. abortus and placental tissue that ultimately culminate in inflammatory pathology and abortion. PMID:25259715

The C2H2-type transcription factor, FlbC, is involved in the transcriptional regulation of Aspergillus oryzae glucoamylase and protease genes specifically expressed in solid-state culture.

Science.gov (United States)

Tanaka, Mizuki; Yoshimura, Midori; Ogawa, Masahiro; Koyama, Yasuji; Shintani, Takahiro; Gomi, Katsuya

2016-07-01

Aspergillus oryzae produces a large amount of secreted proteins in solid-state culture, and some proteins such as glucoamylase (GlaB) and acid protease (PepA) are specifically produced in solid-state culture, but rarely in submerged culture. From the disruption mutant library of A. oryzae transcriptional regulators, we successfully identified a disruption mutant showing an extremely low production level of GlaB but a normal level of α-amylase production. This strain was a disruption mutant of the C2H2-type transcription factor, FlbC, which is reported to be involved in the regulation of conidiospore development. Disruption mutants of other upstream regulators comprising a conidiation regulatory network had no apparent effect on GlaB production in solid-state culture. In addition to GlaB, the production of acid protease in solid-state culture was also markedly decreased by flbC disruption. Northern blot analyses revealed that transcripts of glaB and pepA were significantly decreased in the flbC disruption strain. These results suggested that FlbC is involved in the transcriptional regulation of genes specifically expressed under solid-state cultivation conditions, possibly independent of the conidiation regulatory network.

The Trends of CRP Levels at Different Waist-to-Hip Ratios Among Normotensive Overweight and Obese Patients: A Pilot Study

International Nuclear Information System (INIS)

Firdous, S.

2016-01-01

Objective: To determine the correlation between CRP (C-reactive protein) and Waist to Hip Ratio (WHR) among over weight and obese patients with normal blood pressure. Study Design: An analytical study. Place and Duration of Study: Medical indoor and outpatient clinics of Mayo Hospital, Lahore, from March to August 2013. Methodology: Willing patients with Body Mass Index (BMI) of > 23 kg/m2, normal blood pressures, and age between 18 - 65 years were inducted in the study. Patients with signs of fluid retention, collagen vascular disease, CAD, on corticosteroids, immunomodulators or lipid lowering medications, hypertensives and febrile patients were excluded. Patients were considered to be at low risk for cardiovascular events if WHR among males and females was < 0.95 and < 0.80, respectively. Similarly, males and females with WHR > 1 and > 0.85, respectively were taken as high risk. Levels in-between these ranges were taken as moderate risk. Data was analyzed on SPSS 15. Descriptive statistics were determined. The p-value was calculated by ANOVA and independent sample t-test among males and females respectively, to compare WHR in relation to different CRP levels and < 0.05 was taken as significant. Results: There were 34 male and 74 female patients. The gender-wise mean WHR did not show statistically significant difference categorized CRP levels (p=0.072 in male, and 0.052 in females). There was an increasing trend in CRP levels as WHR increased among females, but this was statistically insignificant (p=0.05). Conclusion: Although the impact of central obesity on cardiac health is well known, however, WHR alone is an unreliable indicator of systemic inflammation and raised CRP level. (author)

A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts.

Science.gov (United States)

Fox, Hannah L; Dembowski, Jill A; DeLuca, Neal A

2017-06-13

Herpes simplex virus 1 (HSV-1) genes are transcribed by cellular RNA polymerase II (RNA Pol II). While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22) function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16) was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes. We further demonstrated that the FACT complex interacts with ICP22 throughout infection. We therefore hypothesized that ICP22 recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes. We reevaluated the phenotype of an ICP22 mutant virus by determining the abundance of all viral mRNAs throughout infection by transcriptome sequencing (RNA-seq). The accumulation of almost all viral mRNAs late in infection was reduced compared to the wild type, regardless of kinetic class. Using chromatin immunoprecipitation sequencing (ChIP-seq), we mapped the location of RNA Pol II on viral genes and found that RNA Pol II levels on the bodies of viral genes were reduced in the ICP22 mutant compared to wild-type virus. In contrast, the association of RNA Pol II with transcription start sites in the mutant was not reduced. Taken together, our results indicate that ICP22 plays a role in recruiting elongation factors like the FACT complex to the HSV-1 genome to allow for efficient viral transcription elongation late in viral infection and ultimately infectious virion production. IMPORTANCE HSV-1 interacts with many cellular proteins throughout productive infection. Here, we demonstrate the interaction of a viral protein, ICP22, with a subset of cellular proteins known to be involved in transcription elongation. We determined that ICP22 is required to recruit the FACT complex and other transcription

Value of a step-up diagnosis plan: CRP and CT-scan to diagnose and manage postoperative complications after major abdominal surgery

Directory of Open Access Journals (Sweden)

Jennifer Straatman

2014-12-01

Full Text Available Postoperative complications frequently follow major abdominal surgery and are associated with increased morbidity and mortality. Early diagnosis and treatment of complications is associated with improved patient outcome. In this study we assessed the value of a step-up diagnosis plan by C-reactive protein and CT-scan (computed tomography-scan imaging for detection of postoperative complications following major abdominal surgery. An observational cohort study was conducted of 399 consecutive patients undergoing major abdominal surgery between January 2009 and January 2011. Indication for operation, type of surgery, postoperative morbidity, complications according to the Clavien-Dindo classification and mortality were recorded. Clinical parameters were recorded until 14 days postoperatively or until discharge. Regular C-reactive protein (CPR measurements in peripheral blood and on indication -enhanced CT-scans were performed. Eighty-three out of 399 (20.6 % patients developed a major complication in the postoperative course after a median of seven days (IQR 4-9 days. One hundred and thirty two patients received additional examination consisting of enhanced CT-scan imaging, and treatment by surgical reintervention or intensive care observation. CRP levels were significantly higher in patients with postoperative complications. On the second postoperative day CRP levels were on average 197.4 mg/L in the uncomplicated group, 220.9 mg/L in patients with a minor complication and 280.1 mg/L in patients with major complications (p < 0,001. CT-scan imaging showed a sensitivity of 91.7 % and specificity of 100 % in diagnosis of major complications. Based on clinical deterioration and the increase of CRP, an additional enhanced CT-scan offered clear discrimination between patients with major abdominal complications and uncomplicated patients. Adequate treatment could then be accomplished.

3. Research Coordination Meeting (RCM) of the Coordinated Research Project (CRP) on 'Studies of advanced reactor technology options for effective incineration of radioactive waste'. Working material

International Nuclear Information System (INIS)

2007-01-01

To meet expressed Member States' needs, the IAEA has initiated a Coordinated Research Project (CRP) on 'Studies of Advanced Reactor Technology Options for Effective Incineration of Radioactive Waste'. The final goal of the CRP is to deepen the understanding of the dynamics of transmutation systems, e.g. the accelerator driven system, especially systems with deteriorated safety parameters, qualify the available methods, specify the range of validity of methods, and formulate requirements for future theoretical developments. Should transient experiments be available, the CRP will pursue experimental benchmarking work. In any case, based on the results, the CRP will conclude on the potential need of transient experiments and make appropriate proposals for experimental programs. The Technical Meeting in Chennai was the 3rd Research Coordination Meeting (RCM) of the CRP The man objectives of the RCM were to: - Discuss and perform inter-comparisons of the various benchmark results; - Prepare the first draft of the final CRP Report Status of the analyses and inter-comparisons of the results. The main objective of the CRP was to study innovative technology options for incinerating/utilizing radioactive wastes. The CRP's benchmarking exercises focused on eight innovative transmutation 'Domains', which correspond to different critical and sub-critical concepts or groups of concepts: I. Critical fast reactor, solid fuel, with fertile; II. Critical fast reactor, solid fuel, fertile-free; III. ADS, solid fuel, with fertile; IV. ADS, solid fuel, fertile-free; V. Critical reactor and ADS, molten salt fuel, with fertile; VI. Critical reactor and ADS, molten salt fuel, fertile-free; VII. Critical fast reactor and ADS, gas cooled; VIII. Fusion/fission hybrid system. For each of these Domains, the discussions and inter-comparisons considered the following issues: - Reactor-models; - Scenarios/phenomena; - Static analyses; - Dynamic analyses; - Methods; - Codes; - Neutronic data base

Association of variants of transcription factor 7-like 2 (TCF7L2) with susceptibility to type 2 diabetes in the Dutch Breda cohort

NARCIS (Netherlands)

van Vliet-Ostaptchouk, J.V.; Shiri-Sverdlov, R.; Zhernakova, A.; Strengman, E.; van Haeften, T.W.; Hofker, M.H.; Wijmenga, C.

Aim/hypothesis A strong association between susceptibility to type 2 diabetes and common variants of transcription factor 7-like 2 (TCF7L2), encoding an enteroendocrine transcription factor involved in glucose homeostasis, has been reported in three different populations (Iceland, Denmark and USA)

Typing of Poultry Influenza Virus (H5 and H7 by Reverse Transcription- Polymerase Chain Reaction

Directory of Open Access Journals (Sweden)

Cesare Bonacina

2010-01-01

Full Text Available The ability of the influenza Orthomixovirus to undergo to continually antigenically changes that can affect its pathogenicity and its diffusion, explains the growing seriousness of this disease and the recent epizoozies in various parts of the world. There have been 15 HA and 9 NA type A sub-types of the influenza virus identified all of which are present in birds. Until now the very virulent avian influenza viruses identified were all included to the H5 and H7 sub-types. We here show that is possible to identify the H5 and H7 sub-types with reverse transcription-polymerase chain reaction (RT-PCR by using a set of specific primers for each HA sub-type. The RT-PCR is a quick and sensitive method of identifying the HA sub-types of the influenza virus directly from homogenised organs.

Effect of CRP value on 18F-FDG PET vascular positivity in Takayasu arteritis: a systematic review and per-patient based meta-analysis.

Science.gov (United States)

Gomez, Léa; Chaumet-Riffaud, Philippe; Noel, Nicolas; Lambotte, Olivier; Goujard, Cécile; Durand, Emmanuel; Besson, Florent L

2018-04-01

The aim of this study was to quantify the association between the CRP value and 18 F-FDG PET vascular positivity in Takayasu arteritis (TAK) through a structured dedicated systematic review and meta-analysis. From January 2000 to December 2016, the PubMed/MEDLINE database was searched for articles specifically dealing with the assessment of vascular inflammation using 18 F-FDG PET and CRP biomarkers in TAK. Inclusion criteria for the qualitative analysis were (1) 18 F-FDG PET used to assess the disease activity, (2) The use of the ACR criteria for the diagnosis of TAK, (3) No case mixed vasculitis (i.e., no giant cell arteritis), and (4) CRP concentration and clinical disease activity available. For the meta-analysis, PET-positive and PET-negative subgroups with the corresponding CRP concentrations were generated based on per patient data. The standard mean difference, which represents the effect of the CRP concentrations on the 18 F-FDG PET vascular uptake, was computed for all studies, and then the results were pooled together. Among the 33 initial citations, nine complete articles including 210 patients fulfilled the inclusion criteria. Five studies found a significant correlation between the 18 F-FDG PET and CRP concentration, one provided a trend towards association and three did not find any association between the two biomarkers. Six studies found a significant association between 18 F-FDG PET and clinical disease activity, one found a trend towards association and the last two studies did not evaluate this correlation. The meta-analysis (121 patients) provided the following results: Standard Mean Deviation = 0.54 [0.15;0.92]; Chi 2  = 3.35; I 2  = 0%; Test for overall effect: Z = 2.70 (P = 0.007). The CRP concentration only moderately reflects the 18 F-FDG PET vascular positivity in TAK, suggesting dissociated information. Standardized longitudinal prospective studies are necessary to assess the value of 18 F-FDG PET as an independent biomarker for

TACO: a general-purpose tool for predicting cell-type-specific transcription factor dimers.

Science.gov (United States)

Jankowski, Aleksander; Prabhakar, Shyam; Tiuryn, Jerzy

2014-03-19

Cooperative binding of transcription factor (TF) dimers to DNA is increasingly recognized as a major contributor to binding specificity. However, it is likely that the set of known TF dimers is highly incomplete, given that they were discovered using ad hoc approaches, or through computational analyses of limited datasets. Here, we present TACO (Transcription factor Association from Complex Overrepresentation), a general-purpose standalone software tool that takes as input any genome-wide set of regulatory elements and predicts cell-type-specific TF dimers based on enrichment of motif complexes. TACO is the first tool that can accommodate motif complexes composed of overlapping motifs, a characteristic feature of many known TF dimers. Our method comprehensively outperforms existing tools when benchmarked on a reference set of 29 known dimers. We demonstrate the utility and consistency of TACO by applying it to 152 DNase-seq datasets and 94 ChIP-seq datasets. Based on these results, we uncover a general principle governing the structure of TF-TF-DNA ternary complexes, namely that the flexibility of the complex is correlated with, and most likely a consequence of, inter-motif spacing.

A Herpesviral Immediate Early Protein Promotes Transcription Elongation of Viral Transcripts

Directory of Open Access Journals (Sweden)

Hannah L. Fox

2017-06-01

Full Text Available Herpes simplex virus 1 (HSV-1 genes are transcribed by cellular RNA polymerase II (RNA Pol II. While four viral immediate early proteins (ICP4, ICP0, ICP27, and ICP22 function in some capacity in viral transcription, the mechanism by which ICP22 functions remains unclear. We observed that the FACT complex (comprised of SSRP1 and Spt16 was relocalized in infected cells as a function of ICP22. ICP22 was also required for the association of FACT and the transcription elongation factors SPT5 and SPT6 with viral genomes. We further demonstrated that the FACT complex interacts with ICP22 throughout infection. We therefore hypothesized that ICP22 recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes. We reevaluated the phenotype of an ICP22 mutant virus by determining the abundance of all viral mRNAs throughout infection by transcriptome sequencing (RNA-seq. The accumulation of almost all viral mRNAs late in infection was reduced compared to the wild type, regardless of kinetic class. Using chromatin immunoprecipitation sequencing (ChIP-seq, we mapped the location of RNA Pol II on viral genes and found that RNA Pol II levels on the bodies of viral genes were reduced in the ICP22 mutant compared to wild-type virus. In contrast, the association of RNA Pol II with transcription start sites in the mutant was not reduced. Taken together, our results indicate that ICP22 plays a role in recruiting elongation factors like the FACT complex to the HSV-1 genome to allow for efficient viral transcription elongation late in viral infection and ultimately infectious virion production.

Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension

Energy Technology Data Exchange (ETDEWEB)

Moura, Rafaela do Socorro Souza e Silva [Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília, Brasília, DF (Brazil); Vasconcelos, Daniel França [Área de Cardiologia, Faculdade de Medicina, Universidade de Brasília, Brasília, DF (Brazil); Freitas, Eduardo [Departamento de Estatística, Universidade de Brasília, Brasília, DF (Brazil); Moura, Flavio José Dutra de; Rosa, Tânia Torres; Veiga, Joel Paulo Russomano, E-mail: joelprv@unb.br [Área de Clínica Médica, Nefrologia, Faculdade de Medicina, Universidade de Brasília, Brasília, DF (Brazil)

2014-01-15

In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r{sup 2}: 0.277, p < 0.05). CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension.

Cystatin C, CRP, log TG/HDLc and metabolic syndrome are associated with microalbuminuria in hypertension

International Nuclear Information System (INIS)

Moura, Rafaela do Socorro Souza e Silva; Vasconcelos, Daniel França; Freitas, Eduardo; Moura, Flavio José Dutra de; Rosa, Tânia Torres; Veiga, Joel Paulo Russomano

2014-01-01

In patients with systemic hypertension, microalbuminuria is a marker of endothelial damage and is associated with an increased risk for cardiovascular disease. To determine the factors that may lead to the occurrence of microalbuminuria in hypertensive patients with serum creatinine lower than 1.5 mg/dL. This cross-sectional study included 133 Brazilians with essential hypertension followed up at a hypertension outpatient clinic. Those with serum creatinine higher than 1.5 mg/dL, as well as those with diabetes mellitus, were excluded. Systolic and diastolic blood pressures were measured, and body mass index (BMI) and GFR estimated by using the CKD-EPI formula were calculated. The serum levels of the following were assessed: CysC, creatinine, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, C-reactive protein (CRP) and fasting glucose. Microalbuminuria was determined in 24-hour urine. Hypertensive patients were classified according to the presence of one or more criteria for metabolic syndrome. In a multiple regression analysis, the serum levels of CysC and CRP, the atherogenic index log TG/HDLc and the presence of three or more criteria for metabolic syndrome were positively correlated with microalbuminuria (r 2 : 0.277, p < 0.05). CysC, CRP, log TG/HDLc, and the presence of three or more criteria for metabolic syndrome, regardless of serum creatinine, were associated with microalbuminuria, an early marker of kidney damage and cardiovascular risk in patients with essential hypertension

Ferredoxin and ferredoxin-NADP reductase from photosynthetic and nonphotosynthetic tissues of tomato

Science.gov (United States)

Green, L. S.; Yee, B. C.; Buchanan, B. B.; Kamide, K.; Sanada, Y.; Wada, K.

1991-01-01

Ferredoxin and ferredoxin-NADP+ oxidoreductase (FNR) were purified from leaves, roots, and red and green pericarp of tomato (Lycopersicon esculentum, cv VFNT and cv Momotaro). Four different ferredoxins were identified on the basis of N-terminal amino acid sequence and charge. Ferredoxins I and II were the most prevalent forms in leaves and green pericarp, and ferredoxin III was the most prevalent in roots. Red pericarp of the VFNT cv yielded variable amounts of ferredoxins II and III plus a unique form, ferredoxin IV. Red pericarp of the Momotaro cv contained ferredoxins I, II, and IV. This represents the first demonstration of ferredoxin in a chromoplast-containing tissue. There were no major differences among the tomato ferredoxins in absorption spectrum or cytochrome c reduction activity. Two forms of FNR were present in tomato as judged by anion exchange chromatography and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. FNR II had a lower apparent relative molecular weight, a slightly altered absorption spectrum, and a lower specific activity for cytochrome c reduction than FNR I. FNR II could be a partially degraded form of FNR I. The FNRs from the different tissues of tomato plants all showed diaphorase activity, with FNR II being more active than FNR I. The presence of ferredoxin and FNR in heterotrophic tissues of tomato is consistent with the existence of a nonphotosynthetic ferredoxin/FNR redox pathway to support the function of ferredoxin-dependent enzymes.

RNA-guided transcriptional regulation in planta via synthetic dCas9-based transcription factors

KAUST Repository

Piatek, Agnieszka Anna

2014-11-14

Targeted genomic regulation is a powerful approach to accelerate trait discovery and development in agricultural biotechnology. Bacteria and archaea use clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) regulatory systems for adaptive molecular immunity against foreign nucleic acids introduced by invading phages and conjugative plasmids. The type II CRISPR/Cas system has been adapted for genome editing in many cell types and organisms. A recent study used the catalytically inactive Cas9 (dCas9) protein combined with guide-RNAs (gRNAs) as a DNA-targeting platform to modulate gene expression in bacterial, yeast, and human cells. Here, we modified this DNA-targeting platform for targeted transcriptional regulation in planta by developing chimeric dCas9-based transcriptional activators and repressors. To generate transcriptional activators, we fused the dCas9 C-terminus with the activation domains of EDLL and TAL effectors. To generate a transcriptional repressor, we fused the dCas9 C-terminus with the SRDX repression domain. Our data demonstrate that dCas9 fusion with the EDLL activation domain (dCas9:EDLL) and the TAL activation domain (dCas9:TAD), guided by gRNAs complementary to selected promoter elements, induce strong transcriptional activation on Bs3

RNA-guided transcriptional regulation in planta via synthetic dCas9-based transcription factors

KAUST Repository

Piatek, Agnieszka Anna; Ali, Zahir; Baazim, Hatoon; Li, Lixin; Abulfaraj, Aala A.; Alshareef, Sahar; Aouida, Mustapha; Mahfouz, Magdy M.

2014-01-01

Targeted genomic regulation is a powerful approach to accelerate trait discovery and development in agricultural biotechnology. Bacteria and archaea use clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) regulatory systems for adaptive molecular immunity against foreign nucleic acids introduced by invading phages and conjugative plasmids. The type II CRISPR/Cas system has been adapted for genome editing in many cell types and organisms. A recent study used the catalytically inactive Cas9 (dCas9) protein combined with guide-RNAs (gRNAs) as a DNA-targeting platform to modulate gene expression in bacterial, yeast, and human cells. Here, we modified this DNA-targeting platform for targeted transcriptional regulation in planta by developing chimeric dCas9-based transcriptional activators and repressors. To generate transcriptional activators, we fused the dCas9 C-terminus with the activation domains of EDLL and TAL effectors. To generate a transcriptional repressor, we fused the dCas9 C-terminus with the SRDX repression domain. Our data demonstrate that dCas9 fusion with the EDLL activation domain (dCas9:EDLL) and the TAL activation domain (dCas9:TAD), guided by gRNAs complementary to selected promoter elements, induce strong transcriptional activation on Bs3

Transcriptional Silencing of Retroviral Vectors

DEFF Research Database (Denmark)

Lund, Anders Henrik; Duch, M.; Pedersen, F.S.

1996-01-01

. Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral...... transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the t......RNA primer for reverse transcription may have a major influence on transcriptional silencing. Alterations of these elements of the vector backbone as well as the use of internal promoter elements from housekeeping genes may contribute to reduce transcriptional silencing. The use of cell culture and animal...

There Is No Further Gain from Calculating Disease Activity Score in 28 Joints with High Sensitivity Assays of C-Reactive Protein Because of High Intraindividual Variability of CRP: A Cross Sectional Study and Theoretical Consideration

DEFF Research Database (Denmark)

Jensen Hansen, Inger Marie; Asmussen Andreasen, Rikke; Antonsen, Steen

Background/Purpose: The threshold for reporting of C-reactive protein (CRP) differs from laboratory to laboratory. Moreover, CRP values are affected by the intra individual biological variability.[1] With respect to disease activity score in 28 joints (DAS28) and Rheumatoid Arthritis (RA), precise...... threshold for reporting CRP is important due to the direct effects of CRP on calculating DAS28, patient classification and subsequent treatment decisions[2] Methods: This study consists of two sections: a theoretical consideration discussing the performance of CRP in calculating DAS28 with regard...... to the biological variation and reporting limit for CRP and a cross sectional study of all RA patients from our department (n=876) applying our theoretical results. In the second section, we calculate DAS28 twice with actual CRP and CRP=9, the latter to elucidate the positive consequences of changing the lower...

A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians

DEFF Research Database (Denmark)

Wolford, Johanna K; Gruber, Jonathan D; Ossowski, Victoria M

2003-01-01

of diabetes, independent of adiposity. Because CRP is located on 1q21, we considered it a potential positional candidate gene for T2DM. We therefore evaluated CRP and the nearby serum amyloid P-component, APCS, which is structurally similar to CRP, as candidate diabetes susceptibility genes. Approximately 10......Linkage analysis has identified a susceptibility locus for type 2 diabetes mellitus (T2DM) on chromosome 1q21-q23 in several populations. Results from recent prospective studies indicate that increased levels of C-reactive protein (CRP), a marker of immune system activation, are predictive...... disequilibrium clusters. We genotyped representative SNPs in approximately 1300 Pima samples and found a single variant in the CRP promoter (SNP 133552) that was associated with T2DM (P=0.014), as well as a common haplotype (CGCG) that was associated with both T2DM (P=0.029) and corrected insulin response...

Effect of CRP value on {sup 18}F-FDG PET vascular positivity in Takayasu arteritis. A systematic review and per-patient based meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Gomez, Lea; Chaumet-Riffaud, Philippe [Bicetre University Hospital, Department of Biophysics and Nuclear Medicine, Le Kremlin-Bicetre (France); Noel, Nicolas; Lambotte, Olivier [Bicetre University Hospital, Department of Internal Medicine, Le Kremlin-Bicetre (France); Universite Paris Sud, Le Kremlin Bicetre (France); Universite Paris Sud, INSERM UMR 1184, Immunologie des Maladies Virales et Autoimmunes (IMVA), Le Kremlin Bicetre (France); CEA, DSV/iMETI, Division of Immuno-Virology IDMIT, Paris (France); Goujard, Cecile [Bicetre University Hospital, Department of Internal Medicine, Le Kremlin-Bicetre (France); Universite Paris Sud, Le Kremlin Bicetre (France); CEA, DSV/iMETI, Division of Immuno-Virology IDMIT, Paris (France); INSERM U1018, CESP, Le Kremlin Bicetre (France); Durand, Emmanuel; Besson, Florent L. [Bicetre University Hospital, Department of Biophysics and Nuclear Medicine, Le Kremlin-Bicetre (France); Universite Paris Sud, Le Kremlin Bicetre (France); Universite Paris Sud, Universite Paris Saclay, CNRS, IR4M - UMR8081, Orsay (France)

2018-04-15

The aim of this study was to quantify the association between the CRP value and {sup 18}F-FDG PET vascular positivity in Takayasu arteritis (TAK) through a structured dedicated systematic review and meta-analysis. From January 2000 to December 2016, the PubMed/MEDLINE database was searched for articles specifically dealing with the assessment of vascular inflammation using {sup 18}F-FDG PET and CRP biomarkers in TAK. Inclusion criteria for the qualitative analysis were (1) {sup 18}F-FDG PET used to assess the disease activity, (2) The use of the ACR criteria for the diagnosis of TAK, (3) No case mixed vasculitis (i.e., no giant cell arteritis), and (4) CRP concentration and clinical disease activity available. For the meta-analysis, PET-positive and PET-negative subgroups with the corresponding CRP concentrations were generated based on per patient data. The standard mean difference, which represents the effect of the CRP concentrations on the {sup 18}F-FDG PET vascular uptake, was computed for all studies, and then the results were pooled together. Among the 33 initial citations, nine complete articles including 210 patients fulfilled the inclusion criteria. Five studies found a significant correlation between the {sup 18}F-FDG PET and CRP concentration, one provided a trend towards association and three did not find any association between the two biomarkers. Six studies found a significant association between {sup 18}F-FDG PET and clinical disease activity, one found a trend towards association and the last two studies did not evaluate this correlation. The meta-analysis (121 patients) provided the following results: Standard Mean Deviation = 0.54 [0.15;0.92]; Chi{sup 2} = 3.35; I{sup 2} = 0%; Test for overall effect: Z = 2.70 (P = 0.007). The CRP concentration only moderately reflects the {sup 18}F-FDG PET vascular positivity in TAK, suggesting dissociated information. Standardized longitudinal prospective studies are necessary to assess the value of {sup 18}F

Investigating the Effect of Inflammation on Atrial Fibrillation Occurrence by Measuring Highly Sensitive C-reactive Protein (hs-CRP

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Mahdi Hassanzadeh Delui

2014-05-01

Full Text Available Introduction: Atrial fibrillation (AF is the most prevalent cardiac arrhythmias that cardiologists and internists encounter. The goal of this article is to clarify an overview of the evidence linking inflammation to AF existence, which may highlight the effect of some pharmacological agents that have genuine potential to reduce the clinical burden of AF by modulating inflammatory pathways. Materials and Methods: In a case-control study, 50 patients with atrial fibrillation (AF with different etiologies and 50 patients with sinus rhythm and similar bases were selected. Sampling for highly sensitive c-reactive (hs-CRP was done on the patients presenting with AF to the Ghaem hospital between October 2006 and June 2007. Results: Mean age of the patients was 62 years with maximum of 90 and minimum of 36 and standard deviation of 13.80. The most frequent age group was 71-80years. Fifty-four percent of patients were male and 46% were female. Mean serum hs-CRP levels in AF patients with hypertension (HTN ,Ischemic heart disease(IHD, Valvular heart disease (VHD, HTN+IHD and hyperthyroidism were 8.10, 9.40, 8.68, 10.16 and 5.98 mg/Lit; respectively. There was significant difference between hs-CRP levels in hypertensive patients in the two groups (P=0.010. Similar results were observed in IHD patients, VHD patients and HTN+IHD patients in two groups (P=0.015, P=0.037, P=0.000. Conclusion: In addition to some risk factors like baseline cardiac diseases, aging, thyrotoxicosis, pulmonary embolism, pneumonia and cardiac surgery, there also appears to be consistent links between hs-CRP, a marker of inflammation, and the pathogenesis of AF.

Correlation between Interleukin-6 (IL-6, High Sensitivity C-Reactive Protein (hsCRP, Endothelin-1 (ET-1, Asymmetric Dimethylarginine (ADMA and Insulin Resistance (HOMA-IR in Central Obese Men

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Andri Hidayat

2011-04-01

Full Text Available BACKGROUND: Many studies have shown that obesity was closely related to insulin resistance via several pathways such as inflammation, oxidative stress, lipolysis, and endothelial dysfunction. This study was carried out to observe the correlation between inflammation (IL-6 and hsCRP, lipolysis process (ET-1, and endothelial dysfunction (ADMA and insulin resistance (HOMA-IR in centrally obese men. METHODS: This was a cross sectional study on 62 male subjects aged 30–60 years old with waist circumference (WC >90 cm. IL-6, ET-1 and ADMA levels were measured using ELISA method, while hsCRP and insulin were measured using chemiluminescence method. All blood testings were conducted in Prodia Clinical Laboratory. RESULTS: The results showed that WC was significantly correlated with hsCRP (r=0.294, p=0.022, ET-1 (r=0.257, p=0.047 and ADMA (r=0.338, p=0.009. We also found a significant correlation between hsCRP with HOMA-IR (r=0.324, p=0.021, ADMA with HOMA-IR (r=0.280, p=0.045 and IL-6 with hsCRP (r=0.437, p=0.003. CONCLUSIONS: hsCRP and ADMA have significant correlation with HOMA-IR in centrally obese men. HOMA-IR significantly increases in subjects with ADMA above median and either IL-6 or hsCRP above median, as compared to those in the other groups. Inflammation and endothelial dysfunction are important causal pathways of insulin resistance state in centrally obese men. KEYWORDS: obesity, IL-6, hsCRP, ET-1, ADMA, HOMA-IR.

HIGH-SENSITIVITY C-REACTIVE PROTEIN (hsCRP IN YOUNG ADULTS: RELATION TO AEROBIC CAPACITY, PHYSICAL ACTIVITY AND RISK FACTORS FOR CARDIOVASCULAR DISEASES

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K. Mazurek

2011-11-01

Full Text Available Atheromatosis develops as a result of a chronic inflammatory process of the arteries. Inflammatory biomarkers, particularly high-sensitivity C-reactive protein (hsCRP, positively correlate with atheromatosis risk factors and can be used to estimate and predict the risk of cardiovascular events. The purpose of this study was to evaluate the relationship between hsCRP concentration and BMI, body composition, classical risk factors for cardiovascular diseases, energy expenditure for physical activity (WEE and  ·VO2max. 166 volunteers (78 women and 88 men were included in the examinations. Their mean age was 20.2±0.9 years. Health condition was described by the following variables: smoking, WEE,  ·VO2max, body mass index (BMI, waist-to-hip ratio (WHR, fat mass (FM, fat-free mass (FFM, lipid profile, hsCRP, glucose and insulin concentration, and insulin resistance. Between the subgroups created on the basis of hsCRP concentration, in quartiles 1 to 3 and quartile 4, a comparative analysis was carried out. 79.5�0of women and 69.3�0of men had hsCRP values within the references ranges. Moderately high values were found in 14.1�0of women and 22.7�0of men and high in 6.4�0and 7.9�20respectively. Mean values of BMI, FFM, WHR, WEE,  ·VO2max, glucose and triglyceride concentration, and TC/HDL index were significantly lower, while FM and HDL were significantly higher, in women than in men. In the quartile 4 subgroup compared to the quartile 1-3 subgroup, we found significantly lower HDL concentration and a tendency for higher values of BMI (p=0.06 and TC (p=0.07 as well as higher percentages of smoking among men. In young, physically active, healthy persons, serum concentration of hsCRP is not related to physical activity or  ·VO2max.

WTO Compliance Status of the Conservation Security Program (CSP) and the Conservation Reserve Program (CRP)

National Research Council Canada - National Science Library

Schnepf, Randy

2007-01-01

.... This report is not a legal opinion, but describes both the CSP and CRP programs, the WTO Annex II provisions that govern compliance, and the potential issues involved in evaluating the compliance status of the two programs. This report will be updated as events warrant.

Epigenetic control of virulence gene expression in Pseudomonas aeruginosa by a LysR-type transcription regulator.

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Keith H Turner

2009-12-01

Full Text Available Phenotypic variation within an isogenic bacterial population is thought to ensure the survival of a subset of cells in adverse conditions. The opportunistic pathogen Pseudomonas aeruginosa variably expresses several phenotypes, including antibiotic resistance, biofilm formation, and the production of CupA fimbriae. Here we describe a previously unidentified bistable switch in P. aeruginosa. This switch controls the expression of a diverse set of genes, including aprA, which encodes the secreted virulence factor alkaline protease. We present evidence that bistable expression of PA2432, herein named bexR (bistable expression regulator, which encodes a LysR-type transcription regulator, controls this switch. In particular, using DNA microarrays, quantitative RT-PCR analysis, chromatin immunoprecipitation, and reporter gene fusions, we identify genes directly under the control of BexR and show that these genes are bistably expressed. Furthermore, we show that bexR is itself bistably expressed and positively autoregulated. Finally, using single-cell analyses of a GFP reporter fusion, we present evidence that positive autoregulation of bexR is necessary for bistable expression of the BexR regulon. Our findings suggest that a positive feedback loop involving a LysR-type transcription regulator serves as the basis for an epigenetic switch that controls virulence gene expression in P. aeruginosa.

Association between CD8 T-cell subsets and CD4/CD8 ratio with HS-CRP level in HIV-infected patients on antiretroviral therapy

Science.gov (United States)

Isabela, S.; Nugroho, A.; Harijanto, P. N.

2018-03-01

Due to improved access and adherence to antiretroviral therapy (ART), most HIV-infected persons worldwide are predicted to live longer. Nowadays the cause of death for most HIV-infected persons has changed to serious non-AIDS events (SNAEs) which is due to low-grade viremia. HIV patients with ART who had undergone CD4 cell count above 500/uL and there is an increase in hs-CRP despite an undetectable viral load. Some conditions CD8 cells count do not decrease with CD4 cells repairs. We researched in Prof Kandou General Hospital with a total sample of 35 HIV patients who had received ART with the level of CD4>350/uL. CD8 levels, CD4/CD8 ratio, and hs-CRP were assessed. This research is analytic descriptive with cross-sectional study design and analysis uses Spearman correlation. The mean CD8 during the study was 1291.8 (IQR 319-2610cells/uL), the mean ratio of CD4:CD8 was 0.57 (IQR 0.16-1.24) and median hs-CRP is 2.18 (IQR 0.3-6.6mg/dL). There was a significant positive correlation between CD8 and increased hs-CRP (r=0.369, pCD4/CD8 ratio and hs-CRP (r=-0.370, p<0.05).

Evaluation of Hs-CRP levels and interleukin 18 (-137G/C promoter polymorphism in risk prediction of coronary artery disease in first degree relatives.

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Rajesh Kumar G

Full Text Available Coronary Artery Disease (CAD is clearly a multifactorial disease that develops from childhood and ultimately leads to death. Several reports revealed having a First Degree Relatives (FDRS with premature CAD is a significant autonomous risk factor for CAD development. C - reactive protein (CRP is a member of the pentraxin family and is the most widely studied proinflammatory biomarker. IL-18 is a pleiotrophic and proinflammatory cytokine which is produced mainly by macrophages and plays an important role in the inflammatory cascade.Hs-CRP levels were estimated by ELISA and Genotyping of IL-18 gene variant located on promoter -137 (G/C by Allele specific PCR in blood samples of 300 CAD patients and 300 controls and 100 FDRS. Promoter Binding sites and Protein interacting partners were identified by Alibaba 2.1 and Genemania online tools respectively. Hs-CRP levels were significantly high in CAD patients followed by FDRS when compared to controls. In IL-18 -137 (G/C polymorphism homozygous GG is significantly associated with occurrence of CAD and Hs-CRP levels were significantly higher in GG genotype subjects when compared to GC and CC. IL-18 was found to be interacting with 100 protein interactants.Our results indicate that Hs-CRP levels and IL-18-137(G/C polymorphism may help to identify risk of future events of CAD in asymptomatic healthy FDRS.

Evaluation of Hs-CRP levels and interleukin 18 (-137G/C) promoter polymorphism in risk prediction of coronary artery disease in first degree relatives.

Science.gov (United States)

G, Rajesh Kumar; K, Mrudula Spurthi; G, Kishore Kumar; Kurapati, Mohanalatha; M, Saraswati; T, Mohini Aiyengar; P, Chiranjeevi; G, Srilatha Reddy; S, Nivas; P, Kaushik; K, Sanjib Sahu; H, Surekha Rani

2015-01-01

Coronary Artery Disease (CAD) is clearly a multifactorial disease that develops from childhood and ultimately leads to death. Several reports revealed having a First Degree Relatives (FDRS) with premature CAD is a significant autonomous risk factor for CAD development. C - reactive protein (CRP) is a member of the pentraxin family and is the most widely studied proinflammatory biomarker. IL-18 is a pleiotrophic and proinflammatory cytokine which is produced mainly by macrophages and plays an important role in the inflammatory cascade. Hs-CRP levels were estimated by ELISA and Genotyping of IL-18 gene variant located on promoter -137 (G/C) by Allele specific PCR in blood samples of 300 CAD patients and 300 controls and 100 FDRS. Promoter Binding sites and Protein interacting partners were identified by Alibaba 2.1 and Genemania online tools respectively. Hs-CRP levels were significantly high in CAD patients followed by FDRS when compared to controls. In IL-18 -137 (G/C) polymorphism homozygous GG is significantly associated with occurrence of CAD and Hs-CRP levels were significantly higher in GG genotype subjects when compared to GC and CC. IL-18 was found to be interacting with 100 protein interactants. Our results indicate that Hs-CRP levels and IL-18-137(G/C) polymorphism may help to identify risk of future events of CAD in asymptomatic healthy FDRS.

The pat1 protein kinase controls transcription of the mating-type genes in fission yeast

DEFF Research Database (Denmark)

Nielsen, O; Egel, R; Nielsen, Olaf

1990-01-01

. This differentiation process is characterized by a transcriptional induction of the mating-type genes. Conjugation can also be induced in pat1-ts mutants by a shift to a semi-permissive temperature. The pat1 gene encodes a protein kinase, which also functions further downstream in the developmental pathway controlling...... of the mating-type genes in the zygote leads to complete loss of pat1 protein kinase activity causing entry into meiosis. Thus, pat1 can promote its own inactivation. We suggest a model according to which a stepwise inactivation of pat1 leads to sequential derepression of the processes of conjugation......The developmental programme of fission yeast brings about a transition from mitotic cell division to the dormant state of ascospores. In response to nitrogen starvation, two cells of opposite mating type conjugate to form a diploid zygote, which then undergoes meiosis and sporulation...

Overexpression of HMGA2-LPP fusion transcripts promotes expression of the α 2 type XI collagen gene

International Nuclear Information System (INIS)

Kubo, Takahiro; Matsui, Yoshito; Goto, Tomohiro; Yukata, Kiminori; Yasui, Natsuo

2006-01-01

In a subset of human lipomas, a specific t (3; 12) chromosome translocation gives rise to HMGA2-LPP fusion protein, containing the amino (N)-terminal DNA binding domains of HMGA2 fused to the carboxyl (C)-terminal LIM domains of LPP. In addition to its role in adipogenesis, several observations suggest that HMGA2-LPP is linked to chondrogenesis. Here, we analyzed whether HMGA2-LPP promotes chondrogenic differentiation, a marker of which is transactivation of the α 2 type XI collagen gene (Col11a2). Real-time PCR analysis showed that HMGA2-LPP and COL11A2 were co-expressed. Luciferase assay demonstrated that either of HMGA2-LPP, wild-type HMGA2 or the N-terminal HMGA2 transactivated the Col11a2 promoter in HeLa cells, while the C-terminal LPP did not. RT-PCR analysis revealed that HMGA2-LPP transcripts in lipomas with the fusion were 591-fold of full-length HMGA2 transcripts in lipomas without the fusion. These results indicate that in vivo overexpression of HMGA2-LPP promotes chondrogenesis by upregulating cartilage-specific collagen gene expression through the N-terminal DNA binding domains

Relationship between the serum concentrations of C-reactive protein and parameters of adiposity and insulin resistance in patients with type 2 diabetes mellitus

International Nuclear Information System (INIS)

Iwasaki, Tomoyuki; Nakajima, Atsushi; Yoneda, Masato; Terauchi, Yasuo

2006-01-01

Serum C-reactive protein (CRP) concentrations have been reported to be associated with body fat, especially visceral fat accumulation, but most studies up to now have been conducted on non-diabetic subjects. In this study, we investigated the association between the serum CRP concentrations and parameters of adiposity and insulin resistance in both Japanese type 2 diabetes patients and non-diabetic subjects. A total of 248 Japanese subjects (140 type 2 diabetes patients and 108 non-diabetic subjects) were enrolled for the study. The degree of insulin resistance was estimated by the homeostasis model assessment (HOMA-R) method. Fat accumulation was evaluated by measuring visceral and subcutaneous fat areas at the level of the umbilicus in abdominal CT scans. To assess hepatic fat content, the ratio of CT attenuation value of the liver to that of the spleen (L/S ratio) was calculated. Serum CRP was found to be significantly correlated with various indices of adiposity, including L/S ratio, visceral fat area (VFA), subcutaneous fat area (SFA), and HOMA-R, in both the diabetic patients and the non-diabetic subjects. After adjustment for five variables (age, gender, serum CRP, HbAlc, and smoking), serum CRP was still significantly correlated with L/S ratio, VFA, SFA, and HOMA-R in the diabetic patients. We also found that changes in serum CRP concentrations were correlated with changes in the VFA and SFA at 1 year after the baseline in 24 diabetic patients. We conclude that serum CRP may be closely related to the degree of liver steatosis and visceral fat accumulation in Japanese type 2 diabetes mellitus patients. (author)

SUBCLINICAL HYPOTHYROIDISM IN METABOLIC SYNDROME AND ROLE OF CRP IN 50 ADULT PATIENTS

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Pratik Shah

2017-04-01

Full Text Available BACKGROUND Metabolic Syndrome (MetS is generally characterised as a clustering of the abnormal levels of blood lipids (low HDL and high triglycerides, impaired fasting glucose, elevated blood pressure, and excess abdominal obesity. The objectives of the study areTo evaluate presence of Subclinical Hypothyroidism in the study population of the patients with metabolic syndrome. To find out relation between Subclinical Hypothyroidism and different parameters of metabolic syndrome. To evaluate whether patients of metabolic syndrome with raised hs-CRP have an increased risk of having hypothyroidism. MATERIALS AND METHODS A total of 50 adult patients who met with inclusion criteria were selected. Patients with metabolic syndrome (MetS who fulfilled the NCEP-ATP III criteria: 3 out of 5 criteria positive. Patients with liver disorders, renal disorders, congestive cardiac failure, pregnant women, patients on oral contraceptive pills, statins and other medications that alter thyroid functions (e.g. lithium, amiodarone or γ-interferon were excluded from the study. RESULTS A total of 50 patients of metabolic syndrome were enrolled. Out of which 36 were euthyroid, 3 were overt hypothyroid and 11 were subclinical hypothyroid. Out of 11 patients of subclinical hypothyroidism, 9 were female and 2 were male patients. Out of 28 females, 9 (32% were SCH while out of 22 males, 2 (9% were SCH. Out of 50 patients, 3 were overt hypothyroid. All 3 patients had BP >130/85, waist circumference was >88 cm and HDL of 130/85, HDL 150 mg/dL and fasting blood glucose of >100 mg/dL were more associated with male patients. CONCLUSION Subclinical Hypothyroidism was present in 22% of study population and more so in females having metabolic syndrome (32%. Hence, it will be worthwhile to screen female metabolic syndrome patients for thyroid function abnormality. Abnormal blood pressure, triglycerides and HDL cholesterol levels were more associated with subclinical hypothyroidism

CRP-Mediated Carbon Catabolite Regulation of Yersinia pestis Biofilm Formation Is Enhanced by the Carbon Storage Regulator Protein, CsrA.

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Stephan P Willias

Full Text Available The natural transmission of Yersinia pestis is reliant upon biofilm blockage of the flea vector. However, the environmentally-responsive adaptive regulators which facilitate Y. pestis biofilm production in accordance with the flea midgut milieu are not well understood. We seek to establish the impact of available carbon source metabolism and storage upon Y. pestis biofilm production. Our findings demonstrate that Y. pestis biofilm production is subject to carbon catabolite regulation in which the presence of glucose impairs biofilm production; whereas, the sole metabolism of alternate carbon sources promotes robust biofilm formation. This observation is facilitated by the cAMP receptor protein, CRP. In accordance with a stark growth defect, deletion of crp in both CO92 and KIM6+ Y. pestis strains significantly impaired biofilm production when solely utilizing alternate carbon sources. Media supplementation with cAMP, a small-molecule activator of CRP, did not significantly alter Y. pestis biofilm production. Furthermore, CRP did not alter mRNA abundance of previously-characterized hms biofilm synthesis and regulation factors. Therefore, our findings indicate CRP does not confer a direct stimulatory effect, but may indirectly promote Y. pestis biofilm production by facilitating the alternate carbon source expression profile. Additionally, we assessed the impact of the carbon storage regulator protein, CsrA, upon Y. pestis biofilm production. Contrary to what has been described for E. coli, Y. pestis biofilm formation was found to be enhanced by CsrA. Regardless of media composition and available carbon source, deletion of csrA significantly impaired Y. pestis biofilm production. CsrA was found to promote Y. pestis biofilm production independent of glycogen regulation. Loss of csrA did not significantly alter relative hmsH, hmsP, or hmsT mRNA abundance. However, deletion of hmsP in the csrA-deficient mutant enabled excessive biofilm production

Consultancy Meeting on Preparation of the Final Technical Document of the IAEA CRP on Analytical and Experimental Benchmark Analysis of Accelerator Driven Systems

International Nuclear Information System (INIS)

2014-01-01

With the objective to study the major physics phenomena of the spallation source and its coupling to a subcritical system, between 2005 and 2010 the IAEA carried out a Coordinated Research Project (CRP) called “Analytical and Experimental Benchmark Analyses of Accelerator Driven Systems (ADS)”. The CRP was contributed by 27 institutions from 18 Member States (Argentina, Belarus, Belgium, Brazil, China, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Sweden, Ukraine and the USA), which performed a number of analytical and experimental benchmark activities. The main objective of the CRP was to develop, verify and validate calculation tools able to perform detailed ADS calculations, from the high energy proton beam to thermal neutron energies. The purpose of this meeting was to: - Collect and review all the available contributions produced by the CRP participants; - Define structure and content of the final TECDOC; - Assemble the first draft of the TECDOC; - Identify important missing parts; - Distribute tasks and responsibilities for drafting and editing the different sections and sub-sections of the TECDOC; - Agree on the time schedule for the TECDOC finalization, review and publication. The participants were requested to contribute to all the foreseen tasks

The transcription factor Rbf1 is the master regulator for b-mating type controlled pathogenic development in Ustilago maydis.

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Kai Heimel

Full Text Available In the phytopathogenic basidiomycete Ustilago maydis, sexual and pathogenic development are tightly connected and controlled by the heterodimeric bE/bW transcription factor complex encoded by the b-mating type locus. The formation of the active bE/bW heterodimer leads to the formation of filaments, induces a G2 cell cycle arrest, and triggers pathogenicity. Here, we identify a set of 345 bE/bW responsive genes which show altered expression during these developmental changes; several of these genes are associated with cell cycle coordination, morphogenesis and pathogenicity. 90% of the genes that show altered expression upon bE/bW-activation require the zinc finger transcription factor Rbf1, one of the few factors directly regulated by the bE/bW heterodimer. Rbf1 is a novel master regulator in a multilayered network of transcription factors that facilitates the complex regulatory traits of sexual and pathogenic development.

Elements in the transcriptional regulatory region flanking herpes simplex virus type 1 oriS stimulate origin function.

Science.gov (United States)

Wong, S W; Schaffer, P A

1991-05-01

Like other DNA-containing viruses, the three origins of herpes simplex virus type 1 (HSV-1) DNA replication are flanked by sequences containing transcriptional regulatory elements. In a transient plasmid replication assay, deletion of sequences comprising the transcriptional regulatory elements of ICP4 and ICP22/47, which flank oriS, resulted in a greater than 80-fold decrease in origin function compared with a plasmid, pOS-822, which retains these sequences. In an effort to identify specific cis-acting elements responsible for this effect, we conducted systematic deletion analysis of the flanking region with plasmid pOS-822 and tested the resulting mutant plasmids for origin function. Stimulation by cis-acting elements was shown to be both distance and orientation dependent, as changes in either parameter resulted in a decrease in oriS function. Additional evidence for the stimulatory effect of flanking sequences on origin function was demonstrated by replacement of these sequences with the cytomegalovirus immediate-early promoter, resulting in nearly wild-type levels of oriS function. In competition experiments, cotransfection of cells with the test plasmid, pOS-822, and increasing molar concentrations of a competitor plasmid which contained the ICP4 and ICP22/47 transcriptional regulatory regions but lacked core origin sequences resulted in a significant reduction in the replication efficiency of pOS-822, demonstrating that factors which bind specifically to the oriS-flanking sequences are likely involved as auxiliary proteins in oriS function. Together, these studies demonstrate that trans-acting factors and the sites to which they bind play a critical role in the efficiency of HSV-1 DNA replication from oriS in transient-replication assays.

Consultants’ Meeting (Preparatory Meeting) on the IAEA Coordinated Research Project (CRP) “PHENIX End-of-Life Tests”. Working Material

International Nuclear Information System (INIS)

2008-01-01

The overall objective of the CRP is to improve/validate the Member States' analytical capabilities in the field of fast reactor simulation and design. A necessary condition towards achieving this objective is a wide international verification and validation effort of the analysis methodology and codes currently employed in the fields of fast reactor neutronics, thermal hydraulics and plant dynamics to achieve enhanced safety. Therefore, in providing the required wide international basis of interested Member States, each applying different methodologies, the CRP will contribute towards achieving the stated objective with the help of benchmark exercises focusing on the experimental results obtained during the planned PHENIX End-of-Life (EOL) Tests

Correlation of insulin resistance with serum C-reactive protein, adiponectin and leptin levels in patients with type 2 diabetes

International Nuclear Information System (INIS)

Duan Yangqiang; Wang Zuobing; Yu Hui

2012-01-01

Objective: To explore the relationship between serum C-reactive protein (CRP), adiponectin (APN), leptin (Leptin) levels, insulin resistance index (HOMA-IR) and type 2 diabetes mellitus (T2DM) disease susceptibility. Methods: The plasma leptin and insulin (FINS) levels in the DM patients were determined by RIA, and the serum ANP levels were determined by ELSIA. The CRP, conventional serum fasting plasma glucose (FPG) levels were determine by automatic biochemistry analyzer. The insulin resistance index (HOMA-IR, FPG x FINS/22.5) was calculated. The result was analyzed with normal healthy control group. Results: The serum CRP and leptin, HOMA-IR levels in T2DM group were significantly higher than that of in control group (P< 0.01), and the serum ANP was significantly lower than in control group (P<0.01). The HOMA-IR in T2DM was positively correlated with serum CRP (r= 0.36, P<0.05) and leptin(r= 0.39, P<0.05), and was negatively correlated with serum APN (r=0.32, P<0.05). Conclusion: The high serum CRP and leptin and low APN levels hyperlipidaemia might be factors for diabetes, and their metabolic disorders may be closely related with insulin resistance in patients with type 2 diabetes. (authors)

Elevated concentrations of C-reactive protein in subjects with type 2 diabetes mellitus are moderately influenced by glycemic control.

Science.gov (United States)

Rodríguez-Morán, M; Guerrero-Romero, F

2003-03-01

The aim of this study was to establish whether glycemic control results in decrease of C-reactive protein (CRP) in Type 2 diabetic subjects. Newly diagnosed Type 2 diabetic subjects were recruited and followed-up by 6-month intensive medical management. All the participants were carefully interviewed, clinically examined, and laboratory tested to exclude conditions likely to provoke an inflammatory response, which was an exclusion criterium. CRP was measured by automated microparticle enzyme immunoassay (IMx, Abbott Laboratories, USA). Two-hundred and forty-eight patients were included in the analysis of data. At baseline, average CRP levels were of 9.6 +/- 6.2 mg/l. Only 14 (5.7%) patients showed a fasting glucose equal or lower than 6.1 mmo/l (5.6 +/- 0.4 mmo/l); of them, 6 (42.8%) had elevated CRP levels (8.8 +/- 6.7 mg/l). The fasting glucose in the 234 (94.3%) non-controlled subjects was 13.1 +/- 4.8 mmol/l; of them 179 (76.5%) subjects showed elevated CRP levels (10.9 +/- 6.5 mg/I). At the end of the 6-month follow-up, the average fasting glucose and HbA1c in the overall group decreased from 12.5 +/- 5.0 to 9.0 +/- 1.6 mmol/l, p diabetic subjects.

The effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus.

Science.gov (United States)

Arablou, Tahereh; Aryaeian, Naheed; Valizadeh, Majid; Sharifi, Faranak; Hosseini, AghaFatemeh; Djalali, Mahmoud

2014-06-01

To assess the effect of ginger consumption on glycemic status, lipid profile and some inflammatory markers in patients with type 2 diabetes mellitus. In a double-blinded, placebo-controlled clinical trial, 70 type 2 diabetic patients were enrolled. They allocated randomly into ginger group and control group. They consumed 1600 mg ginger versus 1600 mg wheat flour placebo daily for 12 weeks. Serum sugar, lipids, CRP, PGE2 and TNFα were measured before and after intervention. Ginger reduced fasting plasma glucose, HbA1C, insulin, HOMA, triglyceride, total cholesterol, CRP and PGE₂ significantly compared with placebo group (p  0.05). Ginger improved insulin sensitivity and some fractions of lipid profile, and reduced CRP and PGE₂ in type 2 diabetic patients. Therefore ginger can be considered as an effective treatment for prevention of diabetes complications.

A powerful method for transcriptional profiling of specific cell types in eukaryotes: laser-assisted microdissection and RNA sequencing.

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Marc W Schmid

Full Text Available The acquisition of distinct cell fates is central to the development of multicellular organisms and is largely mediated by gene expression patterns specific to individual cells and tissues. A spatially and temporally resolved analysis of gene expression facilitates the elucidation of transcriptional networks linked to cellular identity and function. We present an approach that allows cell type-specific transcriptional profiling of distinct target cells, which are rare and difficult to access, with unprecedented sensitivity and resolution. We combined laser-assisted microdissection (LAM, linear amplification starting from <1 ng of total RNA, and RNA-sequencing (RNA-Seq. As a model we used the central cell of the Arabidopsis thaliana female gametophyte, one of the female gametes harbored in the reproductive organs of the flower. We estimated the number of expressed genes to be more than twice the number reported previously in a study using LAM and ATH1 microarrays, and identified several classes of genes that were systematically underrepresented in the transcriptome measured with the ATH1 microarray. Among them are many genes that are likely to be important for developmental processes and specific cellular functions. In addition, we identified several intergenic regions, which are likely to be transcribed, and describe a considerable fraction of reads mapping to introns and regions flanking annotated loci, which may represent alternative transcript isoforms. Finally, we performed a de novo assembly of the transcriptome and show that the method is suitable for studying individual cell types of organisms lacking reference sequence information, demonstrating that this approach can be applied to most eukaryotic organisms.

Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes

DEFF Research Database (Denmark)

Väremo, Leif; Henriksen, Tora Ida; Scheele, Camilla

2017-01-01

BACKGROUND: Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). The close association between obesity and T2D makes it difficult to isolate specific effects attributed to the disease alone. Therefore, here we set out to identify and characterize...... in sphingolipid metabolism was transcriptionally regulated. CONCLUSIONS: Our findings identify inherent characteristics in myocytes, as a memory of the in vivo phenotype, without the influence from a diabetic or obese extracellular environment, highlighting their importance in the development of T2D....... intrinsic properties of myocytes, associated independently with T2D or obesity. METHODS: We generated and analyzed RNA-seq data from primary differentiated myotubes from 24 human subjects, using a factorial design (healthy/T2D and non-obese/obese), to determine the influence of each specific factor...

Operational impacts of low-enrichment uranium fuel conversion on the Ford Nuclear Reactor

International Nuclear Information System (INIS)

Bernal, F.E.; Brannon, C.C.; Burgard, N.E.; Burn, R.R.; Cook, G.M.; Simpson, P.A.

1985-01-01

The University of Michigan Department of Nuclear Engineering and the Michigan Memorial-Phoenix Project have been engaged in a cooperative effort with Argonne National Laboratory to test and analyze low-enrichment fuel in the Ford Nuclear Reactor (FNR). The effort was begun in 1979, as part of the Reduced Enrichment Research and Test Reactor Program, to demonstrate on a whole-core basis the feasibility of enrichment reduction from 93% to <20% in Materials Test Reactor-type fuel designs. The first low-enrichment uranium (LEU) core was loaded into the FNR and criticality was achieved on December 8, 1981. The final LEU core was established October 11, 1984. No significant operational impacts have resulted from conversion of the FNR to LEU fuel. Thermal flux in the core has decreased slightly; thermal leakage flux has increased. Rod worths, temperature coefficient, and void coefficient have changed imperceptibly. Impressions from the operators are that power defect has increased slightly and that fuel lifetime has increased

An experimental modeling of trinomial bioengineering- crp, rDNA, and transporter engineering within single cell factory for maximizing two-phase bioreduction.

Science.gov (United States)

Basak, Souvik; Ghosh, Sumanta Kumar; Punetha, Vinay Deep; Aphale, Ashish N; Patra, Prabir K; Sahoo, Nanda Gopal

2017-02-01

A carbonyl reductase (cr) gene from Candida glabrata CBS138 has been heterologously expressed in cofactor regenerating E. coli host to convert Ethyl-4-chloro-3-oxobutanoate (COBE) into Ethyl-4-chloro-3-hydroxybutanoate (CHBE). The CR enzyme exhibited marked velocity at substrate concentration as high as 363mM with highest turnover number (112.77±3.95s -1 ). Solitary recombineering of such catalytic cell reproduced CHBE 161.04g/L per g of dry cell weight (DCW). Introduction of combinatorially engineered crp (crp*, F136I) into this heterologous E. coli host yielded CHBE 477.54g/L/gDCW. Furthermore, using nerolidol as exogenous cell transporter, the CHBE productivity has been towered to 710.88g/L/gDCW. The CHBE production has thus been upscaled to 8-12 times than those reported so far. qRT-PCR studies revealed that both membrane efflux channels such as acrAB as well as ROS scavenger genes such as ahpCF have been activated by engineering crp. Moreover, membrane protecting genes such as manXYZ together with solvent extrusion associated genes such as glpC have been upregulated inside mutant host. Although numerous proteins have been investigated to convert COBE to CHBE; this is the first approach to use engineering triad involving crp engineering, recombinant DNA engineering and transporter engineering together for improving cell performance during two-phase biocatalysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Anti-Inflammatory Effects of Zingiber Officinale in Type 2 Diabetic Patients

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Sepide Mahluji

2013-08-01

Full Text Available Purpose: Low-grade inflammation, a common feature in type 2 diabetes (DM2, causes some chronic complications in these patients. The present study was aimed to evaluate the effects of ginger (Zingiber officinale on pro-inflammatory cytokines (IL-6 and TNF-α and the acute phase protein hs-CRP in DM2 patients as a randomized double-blind placebo controlled trial. Methods: A total of 64 DM2 patients randomly were assigned to ginger or placebo groups and received 2 tablets/day of each for 2 months. The concentrations of IL-6, TNF-α and hs-CRP in blood samples were analyzed before and after the intervention. Results: Ginger supplementation significantly reduced the levels of TNF-α (P = 0.006, IL-6 (P = 0.02 and hs-CRP (P = 0.012 in ginger group in comparison to baseline. Moreover, the analysis of covariance showed that the group received ginger supplementation significantly lowered TNF- α (15.3 ± 4.6 vs. 19.6 ± 5.2; P = 0.005 and hs-CRP (2.42 ± 1.7 vs. 2.56 ± 2.18; P = .016 concentrations in comparison to control group. While there were no significant changes in IL-6 (7.9 ± 2.1 vs. 7.8 ± 2.9; P > .05. Conclusion: In conclusion, ginger supplementation in oral administration reduced inflammation in type 2 diabetic patients. So it may be a good remedy to diminish the risk of some chronic complications of diabetes.

Transcriptional Enhancers Induce Insertional Gene Deregulation Independently From the Vector Type and Design

Science.gov (United States)

Maruggi, Giulietta; Porcellini, Simona; Facchini, Giulia; Perna, Serena K; Cattoglio, Claudia; Sartori, Daniela; Ambrosi, Alessandro; Schambach, Axel; Baum, Christopher; Bonini, Chiara; Bovolenta, Chiara; Mavilio, Fulvio; Recchia, Alessandra

2009-01-01

The integration characteristics of retroviral (RV) vectors increase the probability of interfering with the regulation of cellular genes, and account for a tangible risk of insertional mutagenesis in treated patients. To assess the potential genotoxic risk of conventional or self-inactivating (SIN) γ-RV and lentiviral (LV) vectors independently from the biological consequences of the insertion event, we developed a quantitative assay based on real-time reverse transcriptase—PCR on low-density arrays to evaluate alterations of gene expression in individual primary T-cell clones. We show that the Moloney leukemia virus long terminal repeat (LTR) enhancer has the strongest activity in both a γ-RV and a LV vector context, while an internal cellular promoter induces deregulation of gene expression less frequently, at a shorter range and to a lower extent in both vector types. Downregulation of gene expression was observed only in the context of LV vectors. This study indicates that insertional gene activation is determined by the characteristics of the transcriptional regulatory elements carried by the vector, and is largely independent from the vector type or design. PMID:19293778

Comparative genomic reconstruction of transcriptional networks controlling central metabolism in the Shewanella genus

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Kovaleva Galina

2011-06-01

Full Text Available Abstract Background Genome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in bacteria is one of the critical tasks of modern genomics. The Shewanella genus is comprised of metabolically versatile gamma-proteobacteria, whose lifestyles and natural environments are substantially different from Escherichia coli and other model bacterial species. The comparative genomics approaches and computational identification of regulatory sites are useful for the in silico reconstruction of transcriptional regulatory networks in bacteria. Results To explore conservation and variations in the Shewanella transcriptional networks we analyzed the repertoire of transcription factors and performed genomics-based reconstruction and comparative analysis of regulons in 16 Shewanella genomes. The inferred regulatory network includes 82 transcription factors and their DNA binding sites, 8 riboswitches and 6 translational attenuators. Forty five regulons were newly inferred from the genome context analysis, whereas others were propagated from previously characterized regulons in the Enterobacteria and Pseudomonas spp.. Multiple variations in regulatory strategies between the Shewanella spp. and E. coli include regulon contraction and expansion (as in the case of PdhR, HexR, FadR, numerous cases of recruiting non-orthologous regulators to control equivalent pathways (e.g. PsrA for fatty acid degradation and, conversely, orthologous regulators to control distinct pathways (e.g. TyrR, ArgR, Crp. Conclusions We tentatively defined the first reference collection of ~100 transcriptional regulons in 16 Shewanella genomes. The resulting regulatory network contains ~600 regulated genes per genome that are mostly involved in metabolism of carbohydrates, amino acids, fatty acids, vitamins, metals, and stress responses. Several reconstructed regulons including NagR for N-acetylglucosamine catabolism were experimentally validated in S

Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in dutch Caucasians

NARCIS (Netherlands)

Meex, Steven J. R.; van Greevenbroek, Marleen M. J.; Ayoubi, Torik A.; Vlietinck, Robert; van Vliet-Ostaptchouk, Jana V.; Hofker, Martin H.; Vermeulen, Vicky M. M. -J.; Schalkwijk, Casper G.; Feskens, Edith J. M.; Boer, Jolanda M. A.; Stehouwer, Coen D. A.; van der Kallen, Carla J. H.; de Bruin, Tjerk W. A.

Context: Activating transcription factor 6 (ATF6) is critical for initiation and full activation of the unfolded protein response. An association between genetic variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima Indians. Objectives: To investigate the broader significance of

BACH transcription factors in innate and adaptive immunity.

Science.gov (United States)

Igarashi, Kazuhiko; Kurosaki, Tomohiro; Roychoudhuri, Rahul

2017-07-01

BTB and CNC homology (BACH) proteins are transcriptional repressors of the basic region leucine zipper (bZIP) transcription factor family. Recent studies indicate widespread roles of BACH proteins in controlling the development and function of the innate and adaptive immune systems, including the differentiation of effector and memory cells of the B and T cell lineages, CD4 + regulatory T cells and macrophages. Here, we emphasize similarities at a molecular level in the cell-type-specific activities of BACH factors, proposing that competitive interactions of BACH proteins with transcriptional activators of the bZIP family form a common mechanistic theme underlying their diverse actions. The findings contribute to a general understanding of how transcriptional repressors shape lineage commitment and cell-type-specific functions through repression of alternative lineage programmes.

Serratamolide is a hemolytic factor produced by Serratia marcescens.

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Robert M Q Shanks

Full Text Available Serratia marcescens is a common contaminant of contact lens cases and lenses. Hemolytic factors of S. marcescens contribute to the virulence of this opportunistic bacterial pathogen. We took advantage of an observed hyper-hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant serratamolide, previously shown to be a broad-spectrum antibiotic and to contribute to swarming motility. Multicopy expression of swrW or mutation of the hexS transcription factor gene, a known inhibitor of swrW expression, led to an increase in hemolysis. Surfactant zones and expression from an swrW-transcriptional reporter were elevated in a crp mutant compared to the wild type. Purified serratamolide was hemolytic to sheep and murine red blood cells and cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW gene was found in the majority of contact lens isolates tested. Genetic and biochemical analysis implicate the biosurfactant serratamolide as a hemolysin. This novel hemolysin may contribute to irritation and infections associated with contact lens use.

Transcriptional activation of immediate-early gene ETR101 by human T-cell leukaemia virus type I Tax

DEFF Research Database (Denmark)

Chen, Li; Ma, Shiliang; Li, Bo

2003-01-01

Human T-cell leukaemia virus type I (HTLV-I) Tax regulates viral and cellular gene expression through interactions with multiple cellular transcription pathways. This study describes the finding of immediate-early gene ETR101 expression in HTLV-I-infected cells and its regulation by Tax. ETR101...... was persistently expressed in HTLV-I-infected cells but not in HTLV-I uninfected cells. Expression of ETR101 was dependent upon Tax expression in the inducible Tax-expressing cell line JPX-9 and also in Jurkat cells transiently transfected with Tax-expressing vectors. Tax transactivated the ETR101 gene promoter......-DNA complex in HTLV-I-infected cell lines. EMSA with specific antibodies confirmed that the CREB transcription factor was responsible for formation of this specific protein-DNA complex. These results suggested that Tax directly transactivated ETR101 gene expression, mainly through a CRE sequence via the CREB...

GENDER-RELATED DIFFERENCES IN INFLAMMATORY AND LIPID PARAMETERS IN PATIENTS WITH DIABETES MELLITUS TYPE 2

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Boris Djindjic

2008-10-01

Full Text Available Diabetes mellitus type 2 (DM type 2 is one of the most common health problems worldwide. Diabetics have increased risk for development of wide spectrum of atherosclerotic complications, at the basis of which are inflammation and diabetic dyslipidemia. Increasing of relative risk for coronary artery disease development is higher in females with DM type 2.The aim of this study was determination of characteristic inflammatory and lipid disorders in type 2 diabetics and their association with patient gender.The study involved 35 patients with DM type 2 and stable angina pectoris. Besides anamnesis, all patients underwent clinical examinations (measure of blood pressure, body height and weight and calculation of body mass index. Inflammatory markers (sedimentation in I and II hour-SE I and SE II, C reactive protein - CRP, fibrinogen concentration and leukocyte count as well as lipid parameters (total cholesterol, LDL and HDL cholesterol concentration and triglycerides were determined in all the patients.Total cholesterol and triglycerides concentrations were higher in females with DM type 2 compared to males (p<0,05. There were not significant gender differences in HDL and LDL cholesterol concentration. All inflammatory markers (SE I and SE II, CRP, fibrinogen concentration and leukocyte count were higher in females with DM type 2 and CAD compared to men (p<0,05. In males, there was a strong positive correlation between SE I and SE II with total LDL (p<0,05 and HDL cholesterol concentrations (p<0,01. Concentration of CRP was only significantly connected with triglycerides concentration (p<0,05. There was a strong association between leukocyte count and increased triglycerides (p<0,05 and low HDL cholesterol concentration (p<0,01. In females, there was only a strong positive correlation between SE II (p<0,01 and CRP concentration (p<0,05 and triglycerides.Women with DM type 2 and clinically manifest CAD (stable angina pectoris are at higher risk for

Regulation of crp gene expression by the catabolite repressor/activator, Cra, in Escherichia coli.

Science.gov (United States)

Zhang, Zhongge; Aboulwafa, Mohammad; Saier, Milton H

2014-01-01

Growth of E. coli on several carbon sources is dependent on the catabolite repressor/activator (Cra) protein although a Cra consensus DNA-binding site is not present in the control regions of the relevant catabolic operons. We show that Cra regulates growth by activating expression of the crp gene. It thereby mediates catabolite repression of catabolic operons by an indirect mechanism. © 2014 S. Karger AG, Basel.

Genome Binding and Gene Regulation by Stem Cell Transcription Factors

NARCIS (Netherlands)

J.H. Brandsma (Johan)

2016-01-01

markdownabstractNearly all cells of an individual organism contain the same genome. However, each cell type transcribes a different set of genes due to the presence of different sets of cell type-specific transcription factors. Such transcription factors bind to regulatory regions such as promoters

Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription.

Science.gov (United States)

In, K H; Asano, K; Beier, D; Grobholz, J; Finn, P W; Silverman, E K; Silverman, E S; Collins, T; Fischer, A R; Keith, T P; Serino, K; Kim, S W; De Sanctis, G T; Yandava, C; Pillari, A; Rubin, P; Kemp, J; Israel, E; Busse, W; Ledford, D; Murray, J J; Segal, A; Tinkleman, D; Drazen, J M

1997-03-01

Five lipoxygenase (5-LO) is the first committed enzyme in the metabolic pathway leading to the synthesis of the leukotrienes. We examined genomic DNA isolated from 25 normal subjects and 31 patients with asthma (6 of whom had aspirin-sensitive asthma) for mutations in the known transcription factor binding regions and the protein encoding region of the 5-LO gene. A family of mutations in the G + C-rich transcription factor binding region was identified consisting of the deletion of one, deletion of two, or addition of one zinc finger (Sp1/Egr-1) binding sites in the region 176 to 147 bp upstream from the ATG translation start site where there are normally 5 Sp1 binding motifs in tandem. Reporter gene activity directed by any of the mutant forms of the transcription factor binding region was significantly (P < 0.05) less effective than the activity driven by the wild type transcription factor binding region. Electrophoretic mobility shift assays (EMSAs) demonstrated the capacity of wild type and mutant transcription factor binding regions to bind nuclear extracts from human umbilical vein endothelial cells (HUVECs). These data are consistent with a family of mutations in the 5-LO gene that can modify reporter gene transcription possibly through differences in Sp1 and Egr-1 transactivation.

Methodology for the analysis of transcription and translation in transcription-coupled-to-translation systems in vitro.

Science.gov (United States)

Castro-Roa, Daniel; Zenkin, Nikolay

2015-09-15

The various properties of RNA polymerase (RNAP) complexes with nucleic acids during different stages of transcription involve various types of regulation and different cross-talk with other cellular entities and with fellow RNAP molecules. The interactions of transcriptional apparatus with the translational machinery have been focused mainly in terms of outcomes of gene expression, whereas the study of the physical interaction of the ribosome and the RNAP remains obscure partly due to the lack of a system that allows such observations. In this article we will describe the methodology needed to set up a pure, transcription-coupled-to-translation system in which the translocation of the ribosome can be performed in a step-wise manner towards RNAP allowing investigation of the interactions between the two machineries at colliding and non-colliding distances. In the same time RNAP can be put in various types of states, such as paused, roadblocked, backtracked, etc. The experimental system thus allows studying the effects of the ribosome on different aspects of transcription elongation and the effects by RNAP on translation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical significance of determination of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis

International Nuclear Information System (INIS)

Wang Tongwu

2009-01-01

Objective: To explore the clinical significance of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis. Methods: Serum IL-6, saliva secretory IgA (with RIA) and serum hs-CRP (with immuno-tarbility method) levels were measured in 42 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment serum IL-6, hs-CRP and saliva secretory IgA levels in the patients wree significantly higher than those in controls (P 0.05). However, the saliva secreatory IgA levels were still significantly higher than those in controls (P<0.05). Conclusion: There was disturbance of immunomodulation in patients with periodontitis as expressed by the changes of cytokines levels in the course of the diseases. (authors)

Evaluation of the results of the IAEA/FAO CRP on tropical transfer factors

International Nuclear Information System (INIS)

Twining, J.

1998-01-01

Future development of tropical countries will include nuclear power. This is particularly true following the recent attention given to the urgent need to reduce greenhouse gas emissions. From this, it is apparent that there is a need to have the ability to undertake dose assessments within tropical and sub-tropical regions. This includes knowledge of appropriate biological transfer factors for the region. However, most previous transfer factor studies were undertaken within temperate regions, predominantly in the Northern Hemisphere. Following a preliminary data survey, there was thus found to be a paucity of data for tropical and sub-tropical regions (excluding marine ecosystems). In an attempt to rectify this situation, the IAEA and FAO instigated a cooperative research program (CRP) entitled 'Transfer of radionuclides from air, soil and freshwater to the food chain of man in tropical and subtropical environments.' This paper is a synopsis of the findings of the three year CRP project. It is important to recognize that the data used in this presentation are derived from contributors and their colleagues in several countries. A list of chief investigators is given. Dr Martin Frissel, Secretary, European IUR, deserves a special mention for his collation of the CRP data. Some of his figures were used in the presentation or reproduced in this synopsis. The participants undertook regional literature and data surveys, field sampling and experimental investigations. The experimental studies were run by following, as closely as practicable, a suite of standard protocols that helped to reduce variability and errors. The experimental studies comprised two main groups: soil to plant, and: freshwater to fish. Quality assurance on analytical work was performed using intercomparison tests with standard reference materials. The reporting of data was also standardised to facilitate collation and subsequent multivariate statistical analysis. The statistical analysis of the entire

Teaching Typing by Transcription.

Science.gov (United States)

Janson, Eleanor L.

1978-01-01

In addition to discussing the program for teaching typewriting to blind students using the auditory mode, the article presents a sample lesson in print, along with typing rates achieved by earlier classes. (DLS)

In silico and wet lab approaches to study transcriptional regulation

NARCIS (Netherlands)

Hestand, Matthew Scott

2010-01-01

Gene expression is a complicated process with multiple types of regulation, including binding of proteins termed transcription factors. This thesis looks at transcription factors and transcription factor binding site discovery through computational predictions and wet lab work to better elucidate

Sedentary time and markers of inflammation in people with newly diagnosed type 2 diabetes

Science.gov (United States)

Falconer, C.L.; Cooper, A.R.; Walhin, J.P.; Thompson, D.; Page, A.S.; Peters, T.J.; Montgomery, A.A.; Sharp, D.J.; Dayan, C.M.; Andrews, R.C.

2014-01-01

Background and aims We investigated whether objectively measured sedentary time was associated with markers of inflammation in adults with newly diagnosed type 2 diabetes. Methods and results We studied 285 adults (184 men, 101 women, mean age 59.0 ± 9.7) who had been recruited to the Early ACTivity in Diabetes (Early ACTID) randomised controlled trial. C-reactive protein (CRP), adiponectin, soluble intracellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and accelerometer-determined sedentary time and moderate-vigorous physical activity (MVPA) were measured at baseline and after six-months. Linear regression analysis was used to investigate the independent cross-sectional and longitudinal associations of sedentary time with markers of inflammation. At baseline, associations between sedentary time and IL-6 were observed in men and women, an association that was attenuated following adjustment for waist circumference. After 6 months of follow-up, sedentary time was reduced by 0.4 ± 1.2 h per day in women, with the change in sedentary time predicting CRP at follow-up. Every hour decrease in sedentary time between baseline and six-months was associated with 24% (1, 48) lower CRP. No changes in sedentary time between baseline and 6 months were seen in men. Conclusions Higher sedentary time is associated with IL-6 in men and women with type 2 diabetes, and reducing sedentary time is associated with improved levels of CRP in women. Interventions to reduce sedentary time may help to reduce inflammation in women with type 2 diabetes. PMID:24925122

Annotating and quantifying pri-miRNA transcripts using RNA-Seq data of wild type and serrate-1 globular stage embryos of Arabidopsis thaliana

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Daniel Lepe-Soltero

2017-12-01

Full Text Available The genome annotation for the model plant Arabidopsis thaliana does not include the primary transcripts from which MIRNAs are processed. Here we present and analyze the raw mRNA sequencing data from wild type and serrate-1 globular stage embryos of A. thaliana, ecotype Columbia. Because SERRATE is required for pri-miRNA processing, these precursors accumulate in serrate-1 mutants, facilitating their detection using standard RNA-Seq protocols. We first use the mapping of the RNA-Seq reads to the reference genome to annotate the potential primary transcripts of MIRNAs expressed in the embryo. We then quantify these pri-miRNAs in wild type and serrate-1 mutants. Finally, we use differential expression analysis to determine which are up-regulated in serrate-1 compared to wild type, to select the best candidates for bona fide pri-miRNAs expressed in the globular stage embryos. In addition, we analyze a previously published RNA-Seq dataset of wild type and dicer-like 1 mutant embryos at the globular stage [1]. Our data are interpreted and discussed in a separate article [2].

Annotating and quantifying pri-miRNA transcripts using RNA-Seq data of wild type and serrate-1 globular stage embryos of Arabidopsis thaliana.

Science.gov (United States)

Lepe-Soltero, Daniel; Armenta-Medina, Alma; Xiang, Daoquan; Datla, Raju; Gillmor, C Stewart; Abreu-Goodger, Cei

2017-12-01

The genome annotation for the model plant Arabidopsis thaliana does not include the primary transcripts from which MIRNAs are processed. Here we present and analyze the raw mRNA sequencing data from wild type and serrate-1 globular stage embryos of A. thaliana , ecotype Columbia. Because SERRATE is required for pri-miRNA processing, these precursors accumulate in serrate-1 mutants, facilitating their detection using standard RNA-Seq protocols. We first use the mapping of the RNA-Seq reads to the reference genome to annotate the potential primary transcripts of MIRNAs expressed in the embryo. We then quantify these pri-miRNAs in wild type and serrate-1 mutants. Finally, we use differential expression analysis to determine which are up-regulated in serrate-1 compared to wild type, to select the best candidates for bona fide pri-miRNAs expressed in the globular stage embryos. In addition, we analyze a previously published RNA-Seq dataset of wild type and dicer-like 1 mutant embryos at the globular stage [1]. Our data are interpreted and discussed in a separate article [2].

The influence of statin treatment on the inflammatory biomarkers YKL-40 and HsCRP in patients with stable coronary artery disease

DEFF Research Database (Denmark)

Mygind, Naja Dam; Harutyunyan, Marina J; Mathiasen, Anders Bruun

2011-01-01

OBJECTIVE: The inflammatory biomarker YKL-40 is elevated and associated with mortality in patients with stable coronary artery disease (CAD). The aim was to investigate the influence of statin treatment and lipid status on serum YKL-40 and Hs-CRP in patients with stable CAD. DESIGN: Serum YKL-40......, HsCRP, total cholesterol, HDL-c, LDL-c and triglycerides levels were measured in 404 statin treated and in 404 matched non-statin treated patients with stable CAD. RESULTS: YKL-40 was significantly higher in non-statin treated 110 µg/l (median) compared with 65 µg/l in statin treated (p ...

Analysis of Inflammatory Mediators in Prediabetes and Newly Diagnosed Type 2 Diabetes Patients

OpenAIRE

Wang, Zhen; Shen, Xu-Hui; Feng, Wen-Ming; Ye, Guo-fen; Qiu, Wei; Li, Bo

2016-01-01

This study evaluated the inflammatory markers in prediabetes and newly diagnosed type 2 diabetes mellitus (T2DM). Inflammatory markers levels were analyzed using one-way analysis of covariance and the association with prediabetes or T2DM risks was examined by logistic regression models. Our data showed increased levels of hypersensitivity C-reactive protein (hs-CRP), interleukin (IL-4), IL-10, and tryptase in prediabetes subjects and hs-CRP, immunoglobulin E (IgE), IL-4, and IL-10 in T2DM sub...

The human papillomavirus type 11 and 16 E6 proteins modulate the cell-cycle regulator and transcription cofactor TRIP-Br1

International Nuclear Information System (INIS)

Gupta, Sanjay; Takhar, Param Parkash S; Degenkolbe, Roland; Heng Koh, Choon; Zimmermann, Holger; Maolin Yang, Christopher; Guan Sim, Khe; I-Hong Hsu, Stephen; Bernard, Hans-Ulrich

2003-01-01

The genital human papillomaviruses (HPVs) are a taxonomic group including HPV types that preferentially cause genital and laryngeal warts ('low-risk types'), such as HPV-6 and HPV-11, or cancer of the cervix and its precursor lesions ('high-risk types'), such as HPV-16. The transforming processes induced by these viruses depend on the proteins E5, E6, and E7. Among these oncoproteins, the E6 protein stands out because it supports a particularly large number of functions and interactions with cellular proteins, some of which are specific for the carcinogenic HPVs, while others are shared among low- and high-risk HPVs. Here we report yeast two-hybrid screens with HPV-6 and -11 E6 proteins that identified TRIP-Br1 as a novel cellular target. TRIP-Br1 was recently detected by two research groups, which described two separate functions, namely that of a transcriptional integrator of the E2F1/DP1/RB cell-cycle regulatory pathway (and then named TRIP-Br1), and that of an antagonist of the cyclin-dependent kinase suppression of p16INK4a (and then named p34SEI-1). We observed that TRIP-Br1 interacts with low- and high-risk HPV E6 proteins in yeast, in vitro and in mammalian cell cultures. Transcription activation of a complex consisting of E2F1, DP1, and TRIP-Br1 was efficiently stimulated by both E6 proteins. TRIP-Br1 has an LLG E6 interaction motif, which contributed to the binding of E6 proteins. Apparently, E6 does not promote degradation of TRIP-Br1. Our observations imply that the cell-cycle promoting transcription factor E2F1/DP1 is dually targeted by HPV oncoproteins, namely (i) by interference of the E7 protein with repression by RB, and (ii) by the transcriptional cofactor function of the E6 protein. Our data reveal the natural context of the transcription activator function of E6, which has been predicted without knowledge of the E2F1/DP1/TRIP-Br/E6 complex by studying chimeric constructs, and add a function to the limited number of transforming properties shared

C-Reactive Protein Predicts Progression of Peripheral Arterial Disease in Patients with Type 2 Diabetes: A 5-Year Follow-Up Study

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Popović Ljiljana

2014-09-01

Full Text Available Background: Previous studies have indicated that high sensitivity C-reactive protein (hs-CRP is a risk factor for the peripheral arterial disease (PAD in diabetes. This study aimed to evaluate the possible predictive significance of hs-CRP for the development and progression of PAD in patients with type 2 diabetes (T2D.

CRISPR-Cas type I-A Cascade complex couples viral infection surveillance to host transcriptional regulation in the dependence of Csa3b

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He, Fei; Vestergaard, Gisle; Peng, Wenfang; She, Qunxin

2017-01-01

Abstract CRISPR-Cas (clustered regularly interspaced short palindromic repeats and the associated genes) constitute adaptive immune systems in bacteria and archaea and they provide sequence specific immunity against foreign nucleic acids. CRISPR-Cas systems are activated by viral infection. However, little is known about how CRISPR-Cas systems are activated in response to viral infection or how their expression is controlled in the absence of viral infection. Here, we demonstrate that both the transcriptional regulator Csa3b, and the type I-A interference complex Cascade, are required to transcriptionally repress the interference gene cassette in the archaeon Sulfolobus. Csa3b binds to two palindromic repeat sites in the promoter region of the cassette and facilitates binding of the Cascade to the promoter region. Upon viral infection, loading of Cascade complexes onto crRNA-matching protospacers leads to relief of the transcriptional repression. Our data demonstrate a mechanism coupling CRISPR-Cas surveillance of protospacers to transcriptional regulation of the interference gene cassette thereby allowing a fast response to viral infection. PMID:27980065

Lifestyle and clinical factors associated with elevated C-reactive protein among newly diagnosed Type 2 diabetes mellitus patients

DEFF Research Database (Denmark)

Svensson, Elisabeth; Mor, Anil; Rungby, Jørgen

2014-01-01

BACKGROUND: We aimed to examine the prevalence of and modifiable factors associated with elevated C-reactive Protein (CRP), a marker of inflammation, in men and women with newly diagnosed Type 2 Diabetes mellitus (DM) in a population-based setting. METHODS: CRP was measured in 1,037 patients (57...... was primarily elevated among patients with no regular physical activity (aRR 1.5 (95% CI 1.1-1.9)), previous cardiovascular disease (aRR1.5 (95% CI 1.2-1.9) and other comorbidity. For both genders, elevated CRP was 1.4-fold increased in those with weight gain >30 kg since age 20 years. Sensitivity analyses...

Transcriptional control of megakaryocyte development.

Science.gov (United States)

Goldfarb, A N

2007-10-15

Megakaryocytes are highly specialized cells that arise from a bipotent megakaryocytic-erythroid progenitor (MEP). This developmental leap requires coordinated activation of megakaryocyte-specific genes, radical changes in cell cycle properties, and active prevention of erythroid differentiation. These programs result from upregulation of megakaryocyte-selective transcription factors, downregulation of erythroid-selective transcription factors and ongoing mediation of common erythro-megakaryocytic transcription factors. Unlike most developmental programs, no single lineage-unique family of master regulators exerts executive control over the megakaryocytic plan. Rather, an assemblage of non-unique factors and signals converge to determine lineage and differentiation. In human megakaryopoiesis, hereditary disorders of platelet production have confirmed contributions from three distinct transcription factor families. Murine models have extended this repertoire to include multiple additional factors. At a mechanistic level, the means by which these non-unique factors collaborate in the establishment of a perfectly unique cell type remains a central question.

Reduced Neuronal Transcription of Escargot, the Drosophila Gene Encoding a Snail-Type Transcription Factor, Promotes Longevity

Science.gov (United States)

Symonenko, Alexander V.; Roshina, Natalia V.; Krementsova, Anna V.; Pasyukova, Elena G.

2018-01-01

In recent years, several genes involved in complex neuron specification networks have been shown to control life span. However, information on these genes is scattered, and studies to discover new neuronal genes and gene cascades contributing to life span control are needed, especially because of the recognized role of the nervous system in governing homeostasis, aging, and longevity. Previously, we demonstrated that several genes that encode RNA polymerase II transcription factors and that are involved in the development of the nervous system affect life span in Drosophila melanogaster. Among other genes, escargot (esg) was demonstrated to be causally associated with an increase in the life span of male flies. Here, we present new data on the role of esg in life span control. We show that esg affects the life spans of both mated and unmated males and females to varying degrees. By analyzing the survival and locomotion of the esg mutants, we demonstrate that esg is involved in the control of aging. We show that increased longevity is caused by decreased esg transcription. In particular, we demonstrate that esg knockdown in the nervous system increased life span, directly establishing the involvement of the neuronal esg function in life span control. Our data invite attention to the mechanisms regulating the esg transcription rate, which is changed by insertions of DNA fragments of different sizes downstream of the structural part of the gene, indicating the direction of further research. Our data agree with the previously made suggestion that alterations in gene expression during development might affect adult lifespan, due to epigenetic patterns inherited in cell lineages or predetermined during the development of the structural and functional properties of the nervous system. PMID:29760717

Inflammatory Biomarkers of Cardiometabolic Risk in Obese Egyptian Type 2 Diabetics

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Lamiaa A. A. Barakat

2017-11-01

Full Text Available Inflammatory biomarkers provide a minimally invasive means for early detection and specific treatment of metabolic syndrome and related disorders. The objective of this work was to search for inflammatory biomarkers of cardiometabolic risk in obese type 2 diabetics. The study was performed on 165 persons attending the medical outpatient clinic of Ismailia General Hospital. Their mean age was (50.69 ± 10.15 years. They were divided into three groups. The control group was composed of 55 non-obese, non-diabetic healthy volunteers, 32 males and 23 females. Two study groups were included in this study: group 2 was composed of 55 obese, non-diabetic subjects, 25 males and 30 females matched for age and gender. All patients including the control were subjected to clinical history taking, a clinical examination for the measurement of body mass index (BMI. Investigations were carried out for fasting blood glucose, fasting serum insulin, insulin resistance (IR, the lipid profile, lipoprotein band lipoprotein phospholipase A2, and non-high-density lipoprotein cholesterol (non-HDL-C. Urea, albumin and creatinine analysis and liver function tests were performed, and a complete blood count (CBC was taken. Hemoglobin A1C (HbA1C, serum high-sensitivity C-reactive protein (hs-CRP, interleukin-6 (IL-6 and tumor necrosis factor-α (TNF-α were tested. There were statistically significant differences among the studied groups in terms of total cholesterol, non-HDL-C, high-density lipoprotein cholesterol (HDL-C, triglycerides (TG, low-density lipoprotein cholesterol (LDL-C, lipoprotein-associated phospholipase A2 and apolipoprotein B. The inflammatory biomarkers hs-CRP, IL-6 and TNF-α were significantly statistically increased in the study groups by (1.62 ± 0.99, 2.32 ± 1.11, (1.73 ± 1.14, 2.53 ± 1.34, and (1.87 ± 1.09, 2.17 ± 0.89 respectively, where p < 0.01. Significant positive correlation was found between Homeostatic Model Assessment (HOMA-IR, hs-CRP

Diagnostic value of soluble CD163 serum levels in patients suspected of meningitis: comparison with CRP and procalcitonin

DEFF Research Database (Denmark)

Knudsen, Troels Bygum; Larsen, Klaus; Kristiansen, Thomas Birk

2007-01-01

CD163. However, sCD163 may be helpful in rapid identification of patients with systemic bacterial infection. If used as an adjunct to lumbar puncture, PCT and CRP had very high diagnostic accuracy for distinguishing between bacterial and viral infection in patients with spinal fluid pleocytosis. However......-operating characteristic AUCs (areas under curves). Patients were classified by 2 sets of diagnostic criteria into: A) purulent meningitis, serous meningitis or non-meningitis, and B) systemic bacterial infection, local bacterial infection or non-bacterial disease. An elevated serum level of sCD163 was the most specific......The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected...

CCS mRNA transcripts and serum CCS protein as copper marker in adults suffering inflammatory processes.

Science.gov (United States)

Araya, Magdalena; Gutiérrez, Ricardo; Arredondo, Miguel

2014-08-01

The chaperone to Zn-Cu superoxide dismutase (CCS) has been postulated as a candidate copper indicator, changing in a consistent manner in induced and recovered copper deficiency, in experimental cell and animal models. In real life people have various conditions that may modify molecules acting as acute phase proteins, such as serum ceruloplasmin and copper concentration and could alter CCS responses. With the hypothesis that CCS mRNA transcripts and protein would be different in individuals suffering inflammatory processes in comparison to healthy individuals, we assessed adult individuals who, although not ill had conditions known to induce variable degrees of inflammation. Screening of 600 adults resulted in two study groups, formed on the basis of their clinical history and levels of serum C reactive protein (CRP): Group 1 (n = 61, mean (range) CRP = 0.9 (0.3-2.0 mg/dL) and Group 2 (n = 150, mean (range) CRP = 6.1 (4.3-8.7 mg/dL). Results showed that mRNA transcripts relative abundance was not different for CCS, MTIIA, TNF-alpha and Cu-Zn-SOD by group (p > 0.05, one way Anova), nor between sexes (p > 0.05, one way Anova). Distribution of CCS mRNA transcripts and CCS protein in serum did not show any differences or trends. Results disproved our hypothesis that CCS abundance of transcripts and CCS protein would be different in individuals suffering inflammatory processes, adding further support to the idea that CCS may be a copper marker.

A Herpes Simplex Virus Type 1 Mutant Expressing a Baculovirus Inhibitor of Apoptosis Gene in Place of Latency-Associated Transcript Has a Wild-Type Reactivation Phenotype in the Mouse

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Jin, Ling; Perng, Guey-Chuen; Mott, Kevin R.; Osorio, Nelson; Naito, Julia; Brick, David J.; Carpenter, Dale; Jones, Clinton; Wechsler, Steven L.

2005-01-01

The latency-associated transcript (LAT) is essential for the wild-type herpes simplex virus type 1 (HSV-1) high-reactivation phenotype since LAT− mutants have a low-reactivation phenotype. We previously reported that LAT can decrease apoptosis and proposed that this activity is involved in LAT's ability to enhance the HSV-1 reactivation phenotype. The first 20% of the primary 8.3-kb LAT transcript is sufficient for enhancing the reactivation phenotype and for decreasing apoptosis, supporting this proposal. For this study, we constructed an HSV-1 LAT− mutant that expresses the baculovirus antiapoptosis gene product cpIAP under control of the LAT promoter and in place of the LAT region mentioned above. Mice were ocularly infected with this mutant, designated dLAT-cpIAP, and the reactivation phenotype was determined using the trigeminal ganglion explant model. dLAT-cpIAP had a reactivation phenotype similar to that of wild-type virus and significantly higher than that of (i) the LAT− mutant dLAT2903; (ii) dLAT1.5, a control virus containing the same LAT deletion as dLAT-cpIAP, but with no insertion of foreign DNA, thereby controlling for potential readthrough transcription past the cpIAP insert; and (iii) dLAT-EGFP, a control virus identical to dLAT-cpIAP except that it contained the enhanced green fluorescent protein open reading frame (ORF) in place of the cpIAP ORF, thereby controlling for expression of a random foreign gene instead of the cpIAP gene. These results show that an antiapoptosis gene with no sequence similarity to LAT can efficiently substitute for the LAT function involved in enhancing the in vitro-induced HSV-1 reactivation phenotype in the mouse. PMID:16160155

FRUITING GENES OF SCHIZOPHYLLUM-COMMUNE ARE TRANSCRIPTIONALLY REGULATED

NARCIS (Netherlands)

SCHUREN, FHJ; VANDERLENDE, TR; WESSELS, JGH

Fruiting genes in Schizophyllum commune are controlled by the mating-type genes and other regulatory genes. To examine whether differential accumulation of mRNAs for these fruiting genes is caused by transcriptional regulation, run-on transcription assaYs were performed with nuclei isolated from

A National Survey of Conservation Reserve Program (CRP) Participants on Environmental Effects, Wildlife Issues, and Vegetation Management on Program Lands

National Research Council Canada - National Science Library

Allen, Arthur

2003-01-01

A national survey of Conservation Reserve Program (CRP) contractees was completed to obtain information about environmental and social effects of the program on participants, farms, and communities...

Combined Atherosclerotic Lesions in Patients with Type 2 Diabetes Mellitus

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L.V. Khimion

2016-04-01

Full Text Available Introduction. Significant prevalence of atherosclerosis and its complications in patients with type 2 diabetes mellitus (DM determines the need for further investigations of existing risk factors. Objective. To determine the effect of various risk factors on the development of atherosclerotic lesions in patients with type 2 DM. Materials and methods. The average levels of systolic blood pressure (SBP, HbA1c, high sensitivity C-reactive protein (hsCRP, uric acid (UA, low density lipoprotein cholesterol (LDL–C in the blood serum and the score by the anxiety and depression scale (HADRS compared to the evaluation of ultrasound data of atherosclerotic lesion of the carotid arteries (intima-media thickness ≥ 0.9 mm or the presence of atherosclerotic plaques and lower limb arteries (ankle-brachial index ≤ 0.9 were analyzed in 122 patients with type 2 DM (66 women, 56 men, mean age — 55.0 (49.8–62.0 years during 5-year follow-up. Statistical analysis was performed using IBM SPSS Statistics 20. Results. During the study, patients were divided into 3 groups: group 1 — 48 people with atherosclerotic lesions of the carotid arteries and lower extremities, group 2 — 47 individuals with atherosclerosis of the carotid arteries, group 3 — 27 people with no signs of atherosclerotic lesion. It was found that in group 1 patients, the average levels of SBP (141.7 (132.1–152.9 mmHg, HbA1c (9.2 (8.2–9.9 %, hsCRP (5.8 (4.2–6.9 mg/L, UA (358.1 (302.4–396.1 μmol/L, LDL–C (4.1 (3.6–5.2 mmol/L, a score by HADRS (16.0 (9.0–18.8 points were significantly higher compared to that of in group 3 (SBP — 136.7 (128.3–143.3 mmHg, HbA1c — 7.7 (7.0–8.4 %, hsCRP — 2.7 (1.1–3.3 mg/L, UA — 276.8 (227.0–316.0 μmol/L, LDL–C — 3.3 (3.0–4.0 mmol/L, a score by HADRS (8.0 (7.0–10.0 points (p < 0.05. The average levels of HbA1c and hsCRP in group 1 patients were significantly higher compared with that of in group 2 (HbA1c — 8.7 (7.6–9

Validity of leptin receptor-deficiency (db/db) type 2 diabetes mellitus mice as a model of secondary osteoporosis

Science.gov (United States)

Huang, Le; You, Yong-Ke; Zhu, Tracy Y.; Zheng, Li-Zhen; Huang, Xiao-Ru; Chen, Hai-Yong; Yao, Dong; Lan, Hui-Yao; Qin, Ling

2016-06-01

This study aimed to evaluate the validation of the leptin receptor-deficient mice model for secondary osteoporosis associated with type 2 diabetes mellitus (T2DM) at bone micro-architectural level. Thirty three 36-week old male mice were divided into four groups: normal control (db/m) (n = 7), leptin receptor-deficient T2DM (db/db) (n = 8), human C-reactive protein (CRP) transgenic normal control (crp/db/m) (n = 7), and human CRP transgenic T2DM (crp/db/db) (n = 11). Lumber vertebrae (L5) and bilateral lower limbs were scanned by micro-CT to analyze trabecular and cortical bone quality. Right femora were used for three-point bending to analyze the mechanical properties. Trabecular bone quality at L5 was better in db/db or crp/db/db group in terms of bone mineral density (BMD), bone volume fraction, connectivity density, trabecular number and separation (all p  0.05). Maximum loading and energy yield in mechanical test were similar among groups while the elastic modulus in db/db and crp/db/db significantly lower than db/m. The leptin-receptor mice is not a proper model for secondary osteoporosis associated with T2DM.

Promoter proximal polyadenylation sites reduce transcription activity

DEFF Research Database (Denmark)

Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

2012-01-01

Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500...

Co-ordinated research project: Comparative international studies of osteoporosis using isotope techniques (CRP: E4.30.06)

International Nuclear Information System (INIS)

2000-01-01

Since the last RCM held in 1996, most participants have made good progress towards the objective of measuring bone mineral density (BMD) in at least 25 subjects of both sexes in each of the 5-year age ranges between 15 and 50 years (i.e. a minimum of 350 subjects in each study group). Some participants have also collected and analysed a number of bone samples, as specified in the protocols for the CRP. One of the most important tasks within the CRP is to 'normalize' the data from different DEXA machines and study centres so as to allow a meaningful comparison of the BMD measurements between centres and study groups. To this end, a European Spine Phantom (ESP) has recently been circulating among the participating centres, who have reported their results to the Central Reference Laboratory (CRL). Central evaluation of the data has so far only been done for a few of the participating centres

The Relationship of Fetuin-A, Adiponectin, Retinol Binding Protein-4 (RBP-4 and High Sensitivity C-Reactive Protein (hsCRP with Insulin Resistance (HOMA-IR in Obese Non Diabetic Men

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Imelda Novianti

2012-04-01

Full Text Available BACKGROUND: Central obesity is the accumulation of visceral (intra-abdominal fat and is strongly known to be associated with insulin resistance and type 2 diabetes mellitus (T2DM. Obesity can cause adipocyte hypertrophy that results in dysregulation of adipokine expression. The abnormal function of adipocytes may play an important role in the development of a chronic low-grade proinflammatory state associated with obesity. Adiponectin, retinol binding protein (RBP-4 and fetuin-A play a role in the pathophysiology of insulin resistance. Expression of fetuin-A is increased due to fat accumulation in the liver. Elevated concentration of fetuin-A in the circulation can impair insulin signaling in muscle and liver as well as suppress adiponectin secretion, although its molecular mechanism is still unclear. The aim of this study was to identify the relationship of fetuin-A, adiponectin, RBP-4 and hsCRP with insulin resistance in obese non diabetic men. METHODS: This was an observational study with a cross-sectional design. The study subjects were 64 men with non diabetic abdominal obesity, characterized by waist circumference of 98.47±5.88 cm and fasting blood glucose of 85.75±8.36 mg/dL. RESULTS: This study showed that fetuin-A was positively correlated with HOMA-IR in obese non diabetic men with insulin resistance (r=0.128; p=0.570, although not significant. Fetuin-A was found to be correlated with adiponectin, RBP-4 and hsCRP (r=0.150; p=0.233; r=0.050; p=0.711; r=-0.04; p=0.445, although not significant. CONCLUSIONS: The concentration of fetuin-A showed a tendency to be positively correlated with HOMA-IR and with RBP-4 in obese non diabetic men, although statistically not significant. The concentration of fetuin-A showed a tendency to be negatively correlated with adiponectin and hsCRP although statistically not significant. There was no interrelationship between fetuin-A, adiponectin, RBP-4, hsCRP and HOMA-IR. Elevated concentrations of fetuin

Analysis of Transcriptional Signatures in Response to Listeria monocytogenes Infection Reveals Temporal Changes That Result from Type I Interferon Signaling

Science.gov (United States)

Potempa, Krzysztof; Graham, Christine M.; Moreira-Teixeira, Lucia; McNab, Finlay W.; Howes, Ashleigh; Stavropoulos, Evangelos; Pascual, Virginia; Banchereau, Jacques; Chaussabel, Damien; O’Garra, Anne

2016-01-01

Analysis of the mouse transcriptional response to Listeria monocytogenes infection reveals that a large set of genes are perturbed in both blood and tissue and that these transcriptional responses are enriched for pathways of the immune response. Further we identified enrichment for both type I and type II interferon (IFN) signaling molecules in the blood and tissues upon infection. Since type I IFN signaling has been reported widely to impair bacterial clearance we examined gene expression from blood and tissues of wild type (WT) and type I IFNαβ receptor-deficient (Ifnar1-/-) mice at the basal level and upon infection with L. monocytogenes. Measurement of the fold change response upon infection in the absence of type I IFN signaling demonstrated an upregulation of specific genes at day 1 post infection. A less marked reduction of the global gene expression signature in blood or tissues from infected Ifnar1-/- as compared to WT mice was observed at days 2 and 3 after infection, with marked reduction in key genes such as Oasg1 and Stat2. Moreover, on in depth analysis, changes in gene expression in uninfected mice of key IFN regulatory genes including Irf9, Irf7, Stat1 and others were identified, and although induced by an equivalent degree upon infection this resulted in significantly lower final gene expression levels upon infection of Ifnar1-/- mice. These data highlight how dysregulation of this network in the steady state and temporally upon infection may determine the outcome of this bacterial infection and how basal levels of type I IFN-inducible genes may perturb an optimal host immune response to control intracellular bacterial infections such as L. monocytogenes. PMID:26918359

Effects of Atorvastatin calcium combined with Aspirin on serum levels of Hcy, NSE, UA, hs-CRP and inflammatory factors of patients with cerebral infarction

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Shu-Qin Zhang

2017-03-01

Full Text Available Objective: To study the effects of Atorvastatin calcium combined with Aspirin on serum levels of homocysteine (Hcy, neuron-specific enolase (NSE, uric acid (UA, high sensitity C-reactive protein (hs-CRP and inflammatory factors of patients with cerebral infarction. Methods: 100 cases of patients with cerebral infarction from March 2014 to May 2016 were treated in the Department of Neurology of our hospital and affiliated to Huazhong University of Science and Technology of traditional Chinese medicine and Western Medicine. The subjects were divided into the control group (n=50 and the treatment group (n=50 randomly. The control group was treated with Aspirin, the treatment group were treated with Atorvastatin calcium combined with Aspirin. The two groups were treated for 28 d. The serum levels of Hcy, NSE, UA, hs- CRP, interleukin-6 (IL-6, interleukin-8 (IL-8 and tumor necrosis factor-α (TNF-α of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum levels of the Hcy, NSE, UA and hs-CRP of the two groups before treatment (P>0.05. After treatment, the serum levels of the Hcy, NSE, UA and hs-CRP of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group (P0.05. After treatment, the serum levels of the IL-6, IL-8 and TNF-α of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group (P<0.05. Conclusions: Atorvastatin calcium combined with Aspirin can significantly reduce the serum levels of Hcy, NSE, UA, hs-CRP, IL-6, IL-8 and TNF-α of the patients with cerebral infarction.

Efficacy of controlled-release KMnO4 (CRP) for controlling dissolved TCE plume in groundwater: a large flow-tank study.

Science.gov (United States)

Lee, Byung Sun; Kim, Jeong Hee; Lee, Ki Churl; Kim, Yang Bin; Schwartz, Franklin W; Lee, Eung Seok; Woo, Nam Chil; Lee, Myoung Ki

2009-02-01

A well-based, reactive barrier system using controlled-release potassium permanganate (CRP system) was recently developed as a long-term treatment option for dilute plumes of chlorinated solvents in groundwater. In this study, we performed large-scale (L x W x D = 8 m x 4 m x 2 m) flow-tank experiments to examine remedial efficacy of the CRP system. A total of 110 CRP rods (OD x L=5 cm x 150 cm) were used to construct a well-based CRP system (L x W x D = 3 m x 4 m x 1.5 m) comprising three discrete barriers installed at 1-m interval downstream. Natural sands having oxidant demand of 3.7 g MnO(4)(-)kg(-1) for 500 mg L(-1)MnO(4)(-) were used as porous media. After MnO(4)(-) concentrations were somewhat stabilized (0.5-6.0 mg L(-1)), trichloroethylene (TCE) plume was flowed through the flow-tank for 53 d by supplying 1.19 m(3)d(-1) of TCE solution. Mean initial TCE concentrations were 87 microg L(-1) for first 20 d and 172 microg L(-1) for the next 33 d. During TCE treatment, flow velocity (0.60md(-1)), pH (7.0-8.2), and concentrations of dissolved metals ([Al]=0.7 mg L(-1), [Fe]=0.01 mg L(-1)) showed little variations. The MnO(2)(s) contents in the sandy media measured after the TCE treatment ranged from 21 to 26 mg kg(-1), slightly increased from mean baseline value of 17 mg kg(-1). Strengths of the TCE plume considerably diminished by the CRP system. For the 87 microg L(-1) plume, TCE concentrations decreased by 38% (53), 67% (29), and 74% (23 microg L(-1)) after 1st, 2nd, and 3rd barriers, respectively. For the 172 microg L(-1) plume, TCE concentrations decreased by 27% (125), 46% (93), and 65% (61 microg L(-1)) after 1st, 2nd, and 3rd barriers, respectively. Incomplete destruction of TCE plume was attributed to the lack of lateral dispersion in the unpumped well-based barrier system. Development of delivery systems that can facilitate lateral spreading and mixing of permanganate with contaminant plume is warranted.

Ferromagnetic nuclear resonance investigation of the surface magnetization in iron sheets

International Nuclear Information System (INIS)

Varga, L.; Tompa, K.

1977-09-01

The role of the domain structure and domain properties in ferromagnetic nuclear resonance (FNR) experiments is reconsidered. Using the FNR signal intensity as a measure of surface domain wall volume, it is found that the behaviour of the surface magnetization differs from that of the bulk magnetization of iron sheets. Namely, a critical field below which the FNR signal remains unchanqed is observed in the surface magnetization. This lag of surface domain wall annihilation is sensitive to the given surface conditions and in particular to the rolling deformation. Considering the small skin depth, FNR as a surface testing method is discussed. (D.P.)

CRP, but not TNF-α or IL-6, decreases after weight loss in patients with morbid obesity exposed to intensive weight reduction and balneological treatment*

Science.gov (United States)

Rość, Danuta; Adamczyk, Przemysław; Boinska, Joanna; Szafkowski, Robert; Ponikowska, Irena; Stankowska, Katarzyna; Góralczyk, Barbara; Ruszkowska-Ciastek, Barbara

2015-01-01

Objective: The aim of this study was to evaluate the concentrations of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the degree of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with morbid obesity exposed to a three-week low-calorie diet and balneotherapy. Methods: The study included 33 patients (25 females and 8 males; mean age 46 years) with body mass index (BMI) values of >40 kg/m2. Evaluations of CRP, IL-6, TNF-α, lipid profile, HOMA-IR, and fasting glucose were carried out before (baseline data) and three weeks after the treatment. The control group consisted of 20 healthy volunteers (15 females and 5 males) with a mean age of 39 years and BMI values of ≤24.9 kg/m2. Results: In the blood of patients with morbid obesity we found significantly elevated levels of CRP, TNF-α, triglycerides, HOMA-IR and fasting glucose, but a decreased level of high density lipoprotein (HDL)-cholesterol, compared with the healthy individuals. The treatment resulted in about a 9.4% reduction in body weight from 122.5 to 111.0 kg and a significant decrease in the concentration of CRP, but no change in TNF-α or IL-6. HOMA-IR was significantly reduced. Conclusions: The decrease in CRP level without changes in TNF-α or IL-6 concentrations after the low-calorie diet and balneological treatment, suggests that an essential amount of adipose tissue must be removed before proper adipocyte function is restored. The decrease in HOMA-IR indicates an improvement in insulin sensitivity, which is beneficial in obese patients. PMID:25990058

Targeted disruption of the mouse Csrp2 gene encoding the cysteine- and glycine-rich LIM domain protein CRP2 result in subtle alteration of cardiac ultrastructure

Directory of Open Access Journals (Sweden)

Stoll Doris

2008-08-01

Full Text Available Abstract Background The cysteine and glycine rich protein 2 (CRP2 encoded by the Csrp2 gene is a LIM domain protein expressed in the vascular system, particularly in smooth muscle cells. It exhibits a bimodal subcellular distribution, accumulating at actin-based filaments in the cytosol and in the nucleus. In order to analyze the function of CRP2 in vivo, we disrupted the Csrp2 gene in mice and analysed the resulting phenotype. Results A ~17.3 kbp fragment of the murine Csrp2 gene containing exon 3 through 6 was isolated. Using this construct we confirmed the recently determined chromosomal localization (Chromosome 10, best fit location between markers D10Mit203 proximal and D10Mit150 central. A gene disruption cassette was cloned into exon 4 and a mouse strain lacking functional Csrp2 was generated. Mice lacking CRP2 are viable and fertile and have no obvious deficits in reproduction and survival. However, detailed histological and electron microscopic studies reveal that CRP2-deficient mice have subtle alterations in their cardiac ultrastructure. In these mice, the cardiomyocytes display a slight increase in their thickness, indicating moderate hypertrophy at the cellular level. Although the expression of several intercalated disc-associated proteins such as β-catenin, N-RAP and connexin-43 were not affected in these mice, the distribution of respective proteins was changed within heart tissue. Conclusion We conclude that the lack of CRP2 is associated with alterations in cardiomyocyte thickness and hypertrophy.

C2H2 type of zinc finger transcription factors in foxtail millet define response to abiotic stresses.

Science.gov (United States)

Muthamilarasan, Mehanathan; Bonthala, Venkata Suresh; Mishra, Awdhesh Kumar; Khandelwal, Rohit; Khan, Yusuf; Roy, Riti; Prasad, Manoj

2014-09-01

C2H2 type of zinc finger transcription factors (TFs) play crucial roles in plant stress response and hormone signal transduction. Hence considering its importance, genome-wide investigation and characterization of C2H2 zinc finger proteins were performed in Arabidopsis, rice and poplar but no such study was conducted in foxtail millet which is a C4 Panicoid model crop well known for its abiotic stress tolerance. The present study identified 124 C2H2-type zinc finger TFs in foxtail millet (SiC2H2) and physically mapped them onto the genome. The gene duplication analysis revealed that SiC2H2s primarily expanded in the genome through tandem duplication. The phylogenetic tree classified these TFs into five groups (I-V). Further, miRNAs targeting SiC2H2 transcripts in foxtail millet were identified. Heat map demonstrated differential and tissue-specific expression patterns of these SiC2H2 genes. Comparative physical mapping between foxtail millet SiC2H2 genes and its orthologs of sorghum, maize and rice revealed the evolutionary relationships of C2H2 type of zinc finger TFs. The duplication and divergence data provided novel insight into the evolutionary aspects of these TFs in foxtail millet and related grass species. Expression profiling of candidate SiC2H2 genes in response to salinity, dehydration and cold stress showed differential expression pattern of these genes at different time points of stresses.

Histone acetyltransferase (HAT) activity of p300 modulates human T lymphotropic virus type 1 p30II-mediated repression of LTR transcriptional activity

International Nuclear Information System (INIS)

Michael, Bindhu; Nair, Amrithraj M.; Datta, Antara; Hiraragi, Hajime; Ratner, Lee; Lairmore, Michael D.

2006-01-01

Human T-lymphotropic virus type-1 (HTLV-1) is a deltaretrovirus that causes adult T cell leukemia/lymphoma, and is implicated in a variety of lymphocyte-mediated inflammatory disorders. HTLV-1 provirus has regulatory and accessory genes in four pX open reading frames. HTLV-1 pX ORF-II encodes two proteins, p13 II and p30 II , which are incompletely defined in virus replication or pathogenesis. We have demonstrated that pX ORF-II mutations block virus replication in vivo and that ORF-II encoded p30 II , a nuclear-localizing protein that binds with CREB-binding protein (CBP)/p300, represses CREB and Tax responsive element (TRE)-mediated transcription. Herein, we have identified p30 II motifs important for p300 binding and in regulating TRE-mediated transcription in the absence and presence of HTLV-1 provirus. Within amino acids 100-179 of p30 II , a region important for repression of LTR-mediated transcription, we identified a single lysine residue at amino acid 106 (K3) that significantly modulates the ability of p30 II to repress TRE-mediated transcription. Exogenous p300, in a dose-responsive manner, reverses p30 II -dependent repression of TRE-mediated transcription, in the absence or presence of the provirus, In contrast to wild type p300, p300 HAT mutants (defective in histone acetyltransferase activity) only partially rescued p30 II -mediated LTR repression. Deacetylation by histone deacetylase-1 (HDAC-1) enhanced p30 II -mediated LTR repression, while inhibition of deacetylation by trichostatin A decreases p30 II -mediated LTR repression. Collectively, our data indicate that HTLV-1 p30 II modulates viral gene expression in a cooperative manner with p300-mediated acetylation

Baseline High-Sensitivity C-Reactive Protein Predicts Macrovascular and Microvascular Complications of Type 2 Diabetes: A Population-Based Study.

Science.gov (United States)

Aryan, Zahra; Ghajar, Alireza; Faghihi-Kashani, Sara; Afarideh, Mohsen; Nakhjavani, Manouchehr; Esteghamati, Alireza

2018-04-25

This prospective study is aimed at examining the predictive value of high-sensitivity C-reactive protein (hs-CRP) for coronary heart disease (CHD) events and microvascular complications of type 2 diabetes mellitus (T2DM). A population-based study (NCT02958579) was conducted on 1,301 participants with T2DM (mean follow-up of 7.5 years). Risk assessment for vascular events was done at baseline, and serum hs-CRP was measured. End points of this study include CHD events, diabetic retinopathy, neuropathy, and diabetic kidney disease. Individuals with unavailable data or hs-CRP >20 mg/L were excluded. The discrimination and reclassification improvement of study end points were tested after addition of hs-CRP to traditional risk factors. Median serum hs-CRP was 2.00 ranging from 0.1 to 17 mg/L. Hazards ratio of each SD increment in baseline hs-CRP was 1.028 (1.024-1.032) for CHD, 1.025 (1.021-1.029) for diabetic neuropathy, 1.037 (1.030-1.043) for diabetic retinopathy, and 1.035 (1.027-1.043) for diabetic kidney disease. The addition of hs-CRP to traditional risk factors of vascular complications of T2DM improved discrimination of all end points (p < 0.001). Net reclassification improvement ranged from 8% for diabetic neuropathy to 31% for diabetic kidney disease (p < 0.05). Baseline hs-CRP predicts both of CHD events and microvascular complications of patients with T2D. © 2018 S. Karger AG, Basel.

Prognostic impact of hs-CRP and IL-6 in patients with persistent atrial fibrillation treated with electrical cardioversion

DEFF Research Database (Denmark)

Henningsen, Kristoffer Mads Aaris; Therkelsen, Susette Krohn; Bruunsgaard, Helle

2009-01-01

OBJECTIVE: The aim of this study was to assess the role of inflammatory processes in the development of atrial fibrillation (AF) and the prognostic impact of inflammatory markers in predicting long-term risk of AF recurrence after electrical cardioversion (CV). METHODS: High-sensitivity C......-reactive protein (hs-CRP) and interleukin-6 (IL-6) were measured in 56 patients with persistent AF (lasting mean 128 days (range 14-960), mean age 65 years (34-84)), 19 healthy volunteers and 19 patients with permanent AF. Patients with persistent AF underwent CV. Blood samples were taken prior to CV and after 1......, 30 and 180 days. RESULTS: The immediate success rate of CV was 88%, while the total recurrence rate after 180 days was 68%. Patients with permanent AF had significantly higher levels of hs-CRP and IL-6 than patients with persistent AF (p = 0.0011, p

Characterization of a spliced exon product of herpes simplex type-1 latency-associated transcript in productively infected cells

International Nuclear Information System (INIS)

Kang, Wen; Mukerjee, Ruma; Gartner, Jared J.; Hatzigeorgiou, Artemis G.; Sandri-Goldin, Rozanne M.; Fraser, Nigel W.

2006-01-01

The latency-associated transcripts (LATs) of herpes simplex virus type-1 (HSV-1) are the only viral RNAs accumulating during latent infections in the sensory ganglia of the peripheral nervous system. The major form of LAT that accumulates in latently infected neurons is a 2 kb intron, spliced from a much less abundant 8.3 primary transcript. The spliced exon mRNA has been hard to detect. However, in this study, we have examined the spliced exon RNA in productively infected cells using ribonuclease protection (RPA), and quantitative RT-PCR (q-PCR) assays. We were able to detect the LAT exon RNA in productively infected SY5Y cells (a human neuronal cell line). The level of the LAT exon RNA was found to be approximately 5% that of the 2 kb intron RNA and thus is likely to be relatively unstable. Quantitative RT-PCR (q-PCR) assays were used to examine the LAT exon RNA and its properties. They confirmed that the LAT exon mRNA is present at a very low level in productively infected cells, compared to the levels of other viral transcripts. Furthermore, experiments showed that the LAT exon mRNA is expressed as a true late gene, and appears to be polyadenylated. In SY5Y cells, in contrast to most late viral transcripts, the LAT exon RNA was found to be mainly nuclear localized during the late stage of a productive infection. Interestingly, more LAT exon RNA was found in the cytoplasm in differentiated compared to undifferentiated SY5Y cells, suggesting the nucleocytoplasmic distribution of the LAT exon RNA and its related function may be influenced by the differentiation state of cells

Post-transcription cleavage generates the 3' end of F17R transcripts in vaccinia virus

International Nuclear Information System (INIS)

D'Costa, Susan M.; Antczak, James B.; Pickup, David J.; Condit, Richard C.

2004-01-01

Most vaccinia virus intermediate and late mRNAs possess 3' ends that are extremely heterogeneous in sequence. However, late mRNAs encoding the cowpox A-type inclusion protein (ATI), the second largest subunit of the RNA polymerase, and the late telomeric transcripts possess homogeneous 3' ends. In the case of the ATI mRNA, it has been shown that the homogeneous 3' end is generated by a post-transcriptional endoribonucleolytic cleavage event. We have determined that the F17R gene also produces homogeneous transcripts generated by a post-transcriptional cleavage event. Mapping of in vivo mRNA shows that the major 3' end of the F17R transcript maps 1262 nt downstream of the F17R translational start site. In vitro transcripts spanning the in vivo 3' end are cleaved in an in vitro reaction using extracts from virus infected cells, and the site of cleavage is the same both in vivo and in vitro. Cleavage is not observed using extract from cells infected in the presence of hydroxyurea; therefore, the cleavage factor is either virus-coded or virus-induced during the post-replicative phase of virus replication. The cis-acting sequence responsible for cleavage is orientation specific and the factor responsible for cleavage activity has biochemical properties similar to the factor required for cleavage of ATI transcripts. Partially purified cleavage factor generates cleavage products of expected size when either the ATI or F17R substrates are used in vitro, strongly suggesting that cleavage of both transcripts is mediated by the same factor

GGRNA: an ultrafast, transcript-oriented search engine for genes and transcripts.

Science.gov (United States)

Naito, Yuki; Bono, Hidemasa

2012-07-01

GGRNA (http://GGRNA.dbcls.jp/) is a Google-like, ultrafast search engine for genes and transcripts. The web server accepts arbitrary words and phrases, such as gene names, IDs, gene descriptions, annotations of gene and even nucleotide/amino acid sequences through one simple search box, and quickly returns relevant RefSeq transcripts. A typical search takes just a few seconds, which dramatically enhances the usability of routine searching. In particular, GGRNA can search sequences as short as 10 nt or 4 amino acids, which cannot be handled easily by popular sequence analysis tools. Nucleotide sequences can be searched allowing up to three mismatches, or the query sequences may contain degenerate nucleotide codes (e.g. N, R, Y, S). Furthermore, Gene Ontology annotations, Enzyme Commission numbers and probe sequences of catalog microarrays are also incorporated into GGRNA, which may help users to conduct searches by various types of keywords. GGRNA web server will provide a simple and powerful interface for finding genes and transcripts for a wide range of users. All services at GGRNA are provided free of charge to all users.

Harnessing CRISPR/Cas systems for programmable transcriptional and post-transcriptional regulation

KAUST Repository

Mahas, Ahmed

2017-11-29

Genome editing has enabled broad advances and novel approaches in studies of gene function and structure; now, emerging methods aim to precisely engineer post-transcriptional processes. Developing precise, efficient molecular tools to alter the transcriptome holds great promise for biotechnology and synthetic biology applications. Different approaches have been employed for targeted degradation of RNA species in eukaryotes, but they lack programmability and versatility, thereby limiting their utility for diverse applications. The CRISPR/Cas9 system has been harnessed for genome editing in many eukaryotic species and, using a catalytically inactive Cas9 variant, the CRISPR/dCas9 system has been repurposed for transcriptional regulation. Recent studies have used other CRISPR/Cas systems for targeted RNA degradation and RNA-based manipulations. For example, Cas13a, a Type VI-A endonuclease, has been identified as an RNA-guided RNA ribonuclease and used for manipulation of RNA. Here, we discuss different modalities for targeted RNA interference with an emphasis on the potential applications of CRISPR/Cas systems as programmable transcriptional regulators for broad uses, including functional biology, biotechnology, and synthetic biology applications.

Harnessing CRISPR/Cas systems for programmable transcriptional and post-transcriptional regulation

KAUST Repository

Mahas, Ahmed; Neal Stewart, C.; Mahfouz, Magdy M.

2017-01-01

Genome editing has enabled broad advances and novel approaches in studies of gene function and structure; now, emerging methods aim to precisely engineer post-transcriptional processes. Developing precise, efficient molecular tools to alter the transcriptome holds great promise for biotechnology and synthetic biology applications. Different approaches have been employed for targeted degradation of RNA species in eukaryotes, but they lack programmability and versatility, thereby limiting their utility for diverse applications. The CRISPR/Cas9 system has been harnessed for genome editing in many eukaryotic species and, using a catalytically inactive Cas9 variant, the CRISPR/dCas9 system has been repurposed for transcriptional regulation. Recent studies have used other CRISPR/Cas systems for targeted RNA degradation and RNA-based manipulations. For example, Cas13a, a Type VI-A endonuclease, has been identified as an RNA-guided RNA ribonuclease and used for manipulation of RNA. Here, we discuss different modalities for targeted RNA interference with an emphasis on the potential applications of CRISPR/Cas systems as programmable transcriptional regulators for broad uses, including functional biology, biotechnology, and synthetic biology applications.

Type 2 diabetes alters metabolic and transcriptional signatures of glucose and amino acid metabolism during exercise and recovery

DEFF Research Database (Denmark)

Hansen, Jakob S; Zhao, Xinjie; Irmler, Martin

2015-01-01

AIMS/HYPOTHESIS: The therapeutic benefit of physical activity to prevent and treat type 2 diabetes is commonly accepted. However, the impact of the disease on the acute metabolic response is less clear. To this end, we investigated the effect of type 2 diabetes on exercise-induced plasma metabolite...... changes and the muscular transcriptional response using a complementary metabolomics/transcriptomics approach. METHODS: We analysed 139 plasma metabolites and hormones at nine time points, and whole genome expression in skeletal muscle at three time points, during a 60 min bicycle ergometer exercise...... and a 180 min recovery phase in type 2 diabetic patients and healthy controls matched for age, percentage body fat and maximal oxygen consumption (VO2). RESULTS: Pathway analysis of differentially regulated genes upon exercise revealed upregulation of regulators of GLUT4 (SLC2A4RG, FLOT1, EXOC7, RAB13...

Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

DEFF Research Database (Denmark)

Ecker, Simone; Chen, Lu; Pancaldi, Vera

2017-01-01

Background: A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. Results: We apply a novel analytical approach to measure and compare transcriptional and epigenetic v...

CRISPR-Cas type I-A Cascade complex couples viral infection surveillance to host transcriptional regulation in the dependence of Csa3b.

Science.gov (United States)

He, Fei; Vestergaard, Gisle; Peng, Wenfang; She, Qunxin; Peng, Xu

2017-02-28

CRISPR-Cas (clustered regularly interspaced short palindromic repeats and the associated genes) constitute adaptive immune systems in bacteria and archaea and they provide sequence specific immunity against foreign nucleic acids. CRISPR-Cas systems are activated by viral infection. However, little is known about how CRISPR-Cas systems are activated in response to viral infection or how their expression is controlled in the absence of viral infection. Here, we demonstrate that both the transcriptional regulator Csa3b, and the type I-A interference complex Cascade, are required to transcriptionally repress the interference gene cassette in the archaeon Sulfolobus. Csa3b binds to two palindromic repeat sites in the promoter region of the cassette and facilitates binding of the Cascade to the promoter region. Upon viral infection, loading of Cascade complexes onto crRNA-matching protospacers leads to relief of the transcriptional repression. Our data demonstrate a mechanism coupling CRISPR-Cas surveillance of protospacers to transcriptional regulation of the interference gene cassette thereby allowing a fast response to viral infection. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Type 3 fimbriae and biofilm formation are regulated by the transcriptional regulators MrkHI in Klebsiella pneumoniae.

Science.gov (United States)

Johnson, Jeremiah G; Murphy, Caitlin N; Sippy, Jean; Johnson, Tylor J; Clegg, Steven

2011-07-01

Klebsiella pneumoniae is an opportunistic pathogen which frequently causes hospital-acquired urinary and respiratory tract infections. K. pneumoniae may establish these infections in vivo following adherence, using the type 3 fimbriae, to indwelling devices coated with extracellular matrix components. Using a colony immunoblot screen, we identified transposon insertion mutants which were deficient for type 3 fimbrial surface production. One of these mutants possessed a transposon insertion within a gene, designated mrkI, encoding a putative transcriptional regulator. A site-directed mutant of this gene was constructed and shown to be deficient for fimbrial surface expression under aerobic conditions. MrkI mutants have a significantly decreased ability to form biofilms on both abiotic and extracellular matrix-coated surfaces. This gene was found to be cotranscribed with a gene predicted to encode a PilZ domain-containing protein, designated MrkH. This protein was found to bind cyclic-di-GMP (c-di-GMP) and regulate type 3 fimbrial expression.

Type 3 Fimbriae and Biofilm Formation Are Regulated by the Transcriptional Regulators MrkHI in Klebsiella pneumoniae▿

Science.gov (United States)

Johnson, Jeremiah G.; Murphy, Caitlin N.; Sippy, Jean; Johnson, Tylor J.; Clegg, Steven

2011-01-01

Klebsiella pneumoniae is an opportunistic pathogen which frequently causes hospital-acquired urinary and respiratory tract infections. K. pneumoniae may establish these infections in vivo following adherence, using the type 3 fimbriae, to indwelling devices coated with extracellular matrix components. Using a colony immunoblot screen, we identified transposon insertion mutants which were deficient for type 3 fimbrial surface production. One of these mutants possessed a transposon insertion within a gene, designated mrkI, encoding a putative transcriptional regulator. A site-directed mutant of this gene was constructed and shown to be deficient for fimbrial surface expression under aerobic conditions. MrkI mutants have a significantly decreased ability to form biofilms on both abiotic and extracellular matrix-coated surfaces. This gene was found to be cotranscribed with a gene predicted to encode a PilZ domain-containing protein, designated MrkH. This protein was found to bind cyclic-di-GMP (c-di-GMP) and regulate type 3 fimbrial expression. PMID:21571997

Sensitivity and Uncertainty Analysis of IAEA CRP HTGR Benchmark Using McCARD

International Nuclear Information System (INIS)

Jang, Sang Hoon; Shim, Hyung Jin

2016-01-01

The benchmark consists of 4 phases starting from the local standalone modeling (Phase I) to the safety calculation of coupled system with transient situation (Phase IV). As a preliminary study of UAM on HTGR, this paper covers the exercise 1 and 2 of Phase I which defines the unit cell and lattice geometry of MHTGR-350 (General Atomics). The objective of these exercises is to quantify the uncertainty of the multiplication factor induced by perturbing nuclear data as well as to analyze the specific features of HTGR such as double heterogeneity and self-shielding treatment. The uncertainty quantification of IAEA CRP HTGR UAM benchmarks were conducted using first-order AWP method in McCARD. Uncertainty of the multiplication factor was estimated only for the microscopic cross section perturbation. To reduce the computation time and memory shortage, recently implemented uncertainty analysis module in MC wielandt calculation was adjusted. The covariance data of cross section was generated by NJOY/ERRORR module with ENDF/B-VII.1. The numerical result was compared with evaluation result of DeCART/MUSAD code system developed by KAERI. IAEA CRP HTGR UAM benchmark problems were analyzed using McCARD. The numerical results were compared with Serpent for eigenvalue calculation and DeCART/MUSAD for S/U analysis. In eigenvalue calculation, inconsistencies were found in the result with ENDF/B-VII.1 cross section library and it was found to be the effect of thermal scattering data of graphite. As to S/U analysis, McCARD results matched well with DeCART/MUSAD, but showed some discrepancy in 238U capture regarding implicit uncertainty.

Uncovering transcriptional interactions via an adaptive fuzzy logic approach

Directory of Open Access Journals (Sweden)

Chen Chung-Ming

2009-12-01

Full Text Available Abstract Background To date, only a limited number of transcriptional regulatory interactions have been uncovered. In a pilot study integrating sequence data with microarray data, a position weight matrix (PWM performed poorly in inferring transcriptional interactions (TIs, which represent physical interactions between transcription factors (TF and upstream sequences of target genes. Inferring a TI means that the promoter sequence of a target is inferred to match the consensus sequence motifs of a potential TF, and their interaction type such as AT or RT is also predicted. Thus, a robust PWM (rPWM was developed to search for consensus sequence motifs. In addition to rPWM, one feature extracted from ChIP-chip data was incorporated to identify potential TIs under specific conditions. An interaction type classifier was assembled to predict activation/repression of potential TIs using microarray data. This approach, combining an adaptive (learning fuzzy inference system and an interaction type classifier to predict transcriptional regulatory networks, was named AdaFuzzy. Results AdaFuzzy was applied to predict TIs using real genomics data from Saccharomyces cerevisiae. Following one of the latest advances in predicting TIs, constrained probabilistic sparse matrix factorization (cPSMF, and using 19 transcription factors (TFs, we compared AdaFuzzy to four well-known approaches using over-representation analysis and gene set enrichment analysis. AdaFuzzy outperformed these four algorithms. Furthermore, AdaFuzzy was shown to perform comparably to 'ChIP-experimental method' in inferring TIs identified by two sets of large scale ChIP-chip data, respectively. AdaFuzzy was also able to classify all predicted TIs into one or more of the four promoter architectures. The results coincided with known promoter architectures in yeast and provided insights into transcriptional regulatory mechanisms. Conclusion AdaFuzzy successfully integrates multiple types of

Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19-9) in gastric cancer

OpenAIRE

Łukaszewicz-Zając, Marta; Mroczko, Barbara; Gryko, Mariusz; Kędra, Bogusław; Szmitkowski, Maciej

2010-01-01

Gastric cancer (GC) is a second most common cause of cancer-related death and represents an inflammation-driven malignancy. It has been suggested that interleukin 6 (IL-6) and C-reactive protein (CRP) play a potential role in the growth and progression of GC. The aim of the present study was to compare clinical significance of IL-6 and CRP with classic tumor markers—carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in GC patients. The study included 92 patients with GC and 70 ...

Identification of concomitant infection with Chlamydia trachomatis IncA-negative mutant and wild-type strains by genomic, transcriptional, and biological characterizations.

Science.gov (United States)

Suchland, Robert J; Jeffrey, Brendan M; Xia, Minsheng; Bhatia, Ajay; Chu, Hencelyn G; Rockey, Daniel D; Stamm, Walter E

2008-12-01

Clinical isolates of Chlamydia trachomatis that lack IncA on their inclusion membrane form nonfusogenic inclusions and have been associated with milder, subclinical infections in patients. The molecular events associated with the generation of IncA-negative strains and their roles in chlamydial sexually transmitted infections are not clear. We explored the biology of the IncA-negative strains by analyzing their genomic structure, transcription, and growth characteristics in vitro and in vivo in comparison with IncA-positive C. trachomatis strains. Three clinical samples were identified that contained a mixture of IncA-positive and -negative same-serovar C. trachomatis populations, and two more such pairs were found in serial isolates from persistently infected individuals. Genomic sequence analysis of individual strains from each of two serovar-matched pairs showed that these pairs were very similar genetically. In contrast, the genome sequence of an unmatched IncA-negative strain contained over 5,000 nucleotide polymorphisms relative to the genome sequence of a serovar-matched but otherwise unlinked strain. Transcriptional analysis, in vitro culture kinetics, and animal modeling demonstrated that IncA-negative strains isolated in the presence of a serovar-matched wild-type strain are phenotypically more similar to the wild-type strain than are IncA-negative strains isolated in the absence of a serovar-matched wild-type strain. These studies support a model suggesting that a change from an IncA-positive strain to the previously described IncA-negative phenotype may involve multiple steps, the first of which involves a translational inactivation of incA, associated with subsequent unidentified steps that lead to the observed decrease in transcript level, differences in growth rate, and differences in mouse infectivity.

Identification of transcription-factor genes expressed in the Arabidopsis female gametophyte

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Kang Il-Ho

2010-06-01

Full Text Available Abstract Background In flowering plants, the female gametophyte is typically a seven-celled structure with four cell types: the egg cell, the central cell, the synergid cells, and the antipodal cells. These cells perform essential functions required for double fertilization and early seed development. Differentiation of these distinct cell types likely involves coordinated changes in gene expression regulated by transcription factors. Therefore, understanding female gametophyte cell differentiation and function will require dissection of the gene regulatory networks operating in each of the cell types. These efforts have been hampered because few transcription factor genes expressed in the female gametophyte have been identified. To identify such genes, we undertook a large-scale differential expression screen followed by promoter-fusion analysis to detect transcription-factor genes transcribed in the Arabidopsis female gametophyte. Results Using quantitative reverse-transcriptase PCR, we analyzed 1,482 Arabidopsis transcription-factor genes and identified 26 genes exhibiting reduced mRNA levels in determinate infertile 1 mutant ovaries, which lack female gametophytes, relative to ovaries containing female gametophytes. Spatial patterns of gene transcription within the mature female gametophyte were identified for 17 transcription-factor genes using promoter-fusion analysis. Of these, ten genes were predominantly expressed in a single cell type of the female gametophyte including the egg cell, central cell and the antipodal cells whereas the remaining seven genes were expressed in two or more cell types. After fertilization, 12 genes were transcriptionally active in the developing embryo and/or endosperm. Conclusions We have shown that our quantitative reverse-transcriptase PCR differential-expression screen is sufficiently sensitive to detect transcription-factor genes transcribed in the female gametophyte. Most of the genes identified in this

Association between ferritin and hepcidin levels and inflammatory status in patients with type 2 diabetes mellitus and obesity.

Science.gov (United States)

Andrews, Mónica; Soto, Néstor; Arredondo-Olguín, Miguel

2015-01-01

The aim of this study was to determine the association between iron parameters and inflammation in obese individuals with and without type 2 diabetes mellitus (T2DM). We studied 132 obese individuals (OB), 60 individuals with T2DM, 106 obese individuals with T2DM (T2DOB), and 146 controls (C). All of were men aged >30 y. Biochemical, iron nutrition, and oxidative stress parameters were determined. Peripheral mononuclear cells were isolated and total RNA was extracted to quantify tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, interleukin (IL)-6, toll-like receptor (TLR)-2/4 and hepcidin by quantitative reverse transcription polymerase chain reaction. OB, T2DM, and T2DOB individuals had higher ferritin, retinol-binding protein 4, and thiobarbituric acid reactive substance (TBAR) levels than controls. T2DOB and T2DM individuals showed high high-sensitivity C-reactive protein (hsCRP) levels and OB with and without T2DM had elevated levels of serum hepcidin. Heme oxygenase activity was high in OB and T2DM and there were no differences observed in superoxide dismutase and glutathione parameters. A correlation between TBARS and ferritin in T2DOB was observed (r = 0.31; P diabetes and obesity with ferritin, TBARS, and hsCRP levels. The upper quartiles of ferritin, TBARS and hepcidin showed an adjusted odd ratio for T2DM of 1.782, 2.250, and 4.370, respectively. TNF-α, IL-6, hepcidin, NF-κB, TLR-2/4 mRNA abundances were increased in T2DM and T2DOB. Elevated hsCRP and hepcidin levels, and increased gene expression of TNF-α, IL-6, NF-κB, and TLR-2/4 in patients with diabetes, obesity, or both exacerbate and perpetuate the insulin resistance and inflammatory state. Copyright © 2015 Elsevier Inc. All rights reserved.

Indian Hedgehog Signaling Regulates Transcription and Expression of Collagen Type X via Runx2/Smads Interactions*

Science.gov (United States)

Amano, Katsuhiko; Densmore, Michael; Nishimura, Riko; Lanske, Beate

2014-01-01

Indian hedgehog (Ihh) is essential for chondrocyte differentiation and endochondral ossification and acts with parathyroid hormone-related peptide in a negative feedback loop to regulate early chondrocyte differentiation and entry to hypertrophic differentiation. Independent of this function, we and others recently reported independent Ihh functions to promote chondrocyte hypertrophy and matrix mineralization in vivo and in vitro. However, the molecular mechanisms for these actions and their functional significance are still unknown. We recently discovered that Ihh overexpression in chondrocytes stimulated the expression of late chondrocyte differentiation markers and induced matrix mineralization. Focusing on collagen type X (Col10α1) expression and transcription, we observed that hedgehog downstream transcription factors GLI-Krüppel family members (Gli) 1/2 increased COL10A1 promoter activity and identified a novel Gli1/2 response element in the 250-bp basic promoter. In addition, we found that Ihh induced Runx2 expression in chondrocytes without up-regulating other modulators of chondrocyte maturation such as Mef2c, Foxa2, and Foxa3. Runx2 promoted Col10α1 expression in cooperation with Ihh. Further analyses using promoter assays, immunofluorescence, and binding assays showed the interaction of Gli1/2 in a complex with Runx2/Smads induces chondrocyte differentiation. Finally, we could demonstrate that Ihh promotes in vitro matrix mineralization using similar molecular mechanisms. Our data provide an in vitro mechanism for Ihh signaling to positively regulate Col10α1 transcription. Thus, Ihh signaling could be an important player for not only early chondrocyte differentiation but maturation and calcification of chondrocytes. PMID:25028519

Effects of Hydroalcoholic Nettle Extract on Insulin Sensitivity and Some Inflammatory Indicator in type 2 Diabetic Patients

Directory of Open Access Journals (Sweden)

N. Namazi

2012-01-01

Full Text Available Introduction & Objective: Diabetes mellitus is a common disease that almost 1.5 million people in Iran are affected, Regarding to the adverse effects of chemical drugs, the tendency to use medicinal plants, among which nettle was chosen to be studied, is growing. In this research the effect of hydroalcoholic extract of nettle on insulin sensitivity and some inflammatory factors in type II diabetic patients were studied.Materials & Methods: A blind randomized clinical trial on 50 men and women with type 2 diabetes; (mean age: 52.39±13.75 was designed to determine the aforementioned effect. Patients were randomly divided into intervention and control groups who received 100 mg/kg, Nettle extract or placebo respectively three times a day for 8 weeks. Fasting Insulin and some inflammatory factors (Interleukin-6 (IL-6, Tumor Necrosis Factor-α (TNF-α, and hsCRP (High Sensitive C-Reactive Protein levels at the beginning and end of the study were measured. Results: IL-6 and hsCRP showed a significant decrease (P <0.05, TNF-α, insulin sensitivity and hsCRP showed no significant change at the end of the study in the intervention group compared to the control. Statistical analysis was performed with SPSS software version 18 and P <0.05 was considered significant for all measurements. Conclusion: The hydroalcoholic extract of nettle showed significant decrease in IL-6 and hsCRP after 2 months of intervention in patients with type 2 diabetes. (Sci J Hamadan Univ Med Sci 2012;18(4:10-14

Tissue-type plasminogen activator and C-reactive protein in acute coronary heart disease. A nested case-control study

DEFF Research Database (Denmark)

Gram, J; Bladbjerg, E-M; Møller, L

2000-01-01

OBJECTIVES: To study the importance of inflammation and fibrinolysis for evolution of ischaemic heart disease in a cohort of initially healthy subjects. DESIGN: Nested case-control study. Follow-up periods 7-15 years. SUBJECTS: Included in the study were 133 cases with coronary heart disease...... and 258 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Subjects with ischaemic heart disease identified in 1991 by the Danish National Hospital Register. Protein concentration of C-reactive protein (CRP) and tissue-type plasminogen activator (t-PA) were measured with ELISA methods in stored serum.......005) and it was present in both the 7-9 years follow-up cohort (CRP: P = 0.014; t-PA: P = 0.001) and the 15 years follow-up cohort (CRP: P = 0.027; t-PA: P = 0.012). The best predictor of CRP was t-PA, whilst the best predictor of t-PA was triglycerides. In a logistic regression analysis model, t-PA still came out...

LocExpress: a web server for efficiently estimating expression of novel transcripts.

Science.gov (United States)

Hou, Mei; Tian, Feng; Jiang, Shuai; Kong, Lei; Yang, Dechang; Gao, Ge

2016-12-22

The temporal and spatial-specific expression pattern of a transcript in multiple tissues and cell types can indicate key clues about its function. While several gene atlas available online as pre-computed databases for known gene models, it's still challenging to get expression profile for previously uncharacterized (i.e. novel) transcripts efficiently. Here we developed LocExpress, a web server for efficiently estimating expression of novel transcripts across multiple tissues and cell types in human (20 normal tissues/cells types and 14 cell lines) as well as in mouse (24 normal tissues/cell types and nine cell lines). As a wrapper to RNA-Seq quantification algorithm, LocExpress efficiently reduces the time cost by making abundance estimation calls increasingly within the minimum spanning bundle region of input transcripts. For a given novel gene model, such local context-oriented strategy allows LocExpress to estimate its FPKMs in hundreds of samples within minutes on a standard Linux box, making an online web server possible. To the best of our knowledge, LocExpress is the only web server to provide nearly real-time expression estimation for novel transcripts in common tissues and cell types. The server is publicly available at http://loc-express.cbi.pku.edu.cn .

Molecular and functional characterization of ferredoxin NADP(H oxidoreductase from Gracilaria chilensis and its complex with ferredoxin

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María Alejandra Vorphal

Full Text Available Abstract Backgroud Ferredoxin NADP(H oxidoreductases (EC 1.18.1.2 (FNR are flavoenzymes present in photosynthetic organisms; they are relevant for the production of reduced donors to redox reactions, i.e. in photosynthesis, the reduction of NADP+ to NADPH using the electrons provided by Ferredoxin (Fd, a small FeS soluble protein acceptor of electrons from PSI in chloroplasts. In rhodophyta no information about this system has been reported, this work is a contribution to the molecular and functional characterization of FNR from Gracilaria chilensis, also providing a structural analysis of the complex FNR/Fd. Methods The biochemical and kinetic characterization of FNR was performed from the enzyme purified from phycobilisomes enriched fractions. The sequence of the gene that codifies for the enzyme, was obtained using primers designed by comparison with sequences of Synechocystis and EST from Gracilaria. 5′RACE was used to confirm the absence of a CpcD domain in FNRPBS of Gracilaria chilensis. A three dimensional model for FNR and Fd, was built by comparative modeling and a model for the complex FNR: Fd by docking. Results The kinetic analysis shows KMNADPH of 12.5 M and a kcat of 86 s−1, data consistent with the parameters determined for the enzyme purified from a soluble extract. The sequence for FNR was obtained and translated to a protein of 33646 Da. A FAD and a NADP+ binding domain were clearly identified by sequence analysis as well as a chloroplast signal sequence. Phycobilisome binding domain, present in some cyanobacteria was absent. Transcriptome analysis of Gch revealed the presence of two Fd; FdL and FdS, sharing the motif CX5CX2CX29X. The analysis indicated that the most probable partner for FNR is FdS. Conclusion The interaction model produced, was consistent with functional properties reported for FNR in plants leaves, and opens the possibilities for research in other rhodophyta of commercial interest.

The Effect of 12 Weeks of High-Intensity Interval Training (HIIT on Homocysteine and CRP Cardiovascular Risk Factors and Body Composition in Overweight Men

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Mohammad Ebrahim Bahram

2016-12-01

Full Text Available Background & Objective: High levels of homocysteine inflammatory markers and C-Reactive Protein (CRP cause many complications, including atherosclerosis, venous thrombosis, and cardiovascular problems. The objective of the present study was to investigate the effect of 12-weekHigh Intensity Interval Training (HIIT on homocysteine, CRP, and body composition in overweight men. Materials & Methods: In this quasi-experimental study, 20 students of Kashan University of Medical Sciences with a body mass index between 25 and 30 kg/m2, were purposefully selected and were randomly divided into experimental and control groups. The experimental group had practiced in the HIIT program with the intensity of up to 90 percent of maximum heart rate for 12 weeks. Before and after exercise, the amount of homocysteine, CRP, weight, body fat percentage, body mass index, and waist-to-hip ratio were calculated. The data were analyzed by using dependent and independent t-test at a significance level of P<0.05. Results: The results showed that12 weeks of HIIT had significant effects on reducing serum levels of homocysteine and HSCRP, body weight, body fat percentage, BMI, and WHR in the experimental group compared to the control group (P<0.05. Conclusion: It seems that 12 weeks of intense interval training as a non-invasive method can have a positive effect on reducing the amount of homocysteine, HS-CRP, and some anthropometric indexes of obesity and overweight.

TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

KAUST Repository

Schaefer, Ulf; Schmeier, Sebastian; Bajic, Vladimir B.

2010-01-01

The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF-DNA binding, protein-protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/. © The Author(s) 2010.

TcoF-DB: dragon database for human transcription co-factors and transcription factor interacting proteins

KAUST Repository

Schaefer, Ulf

2010-10-21

The initiation and regulation of transcription in eukaryotes is complex and involves a large number of transcription factors (TFs), which are known to bind to the regulatory regions of eukaryotic DNA. Apart from TF-DNA binding, protein-protein interaction involving TFs is an essential component of the machinery facilitating transcriptional regulation. Proteins that interact with TFs in the context of transcription regulation but do not bind to the DNA themselves, we consider transcription co-factors (TcoFs). The influence of TcoFs on transcriptional regulation and initiation, although indirect, has been shown to be significant with the functionality of TFs strongly influenced by the presence of TcoFs. While the role of TFs and their interaction with regulatory DNA regions has been well-studied, the association between TFs and TcoFs has so far been given less attention. Here, we present a resource that is comprised of a collection of human TFs and the TcoFs with which they interact. Other proteins that have a proven interaction with a TF, but are not considered TcoFs are also included. Our database contains 157 high-confidence TcoFs and additionally 379 hypothetical TcoFs. These have been identified and classified according to the type of available evidence for their involvement in transcriptional regulation and their presence in the cell nucleus. We have divided TcoFs into four groups, one of which contains high-confidence TcoFs and three others contain TcoFs which are hypothetical to different extents. We have developed the Dragon Database for Human Transcription Co-Factors and Transcription Factor Interacting Proteins (TcoF-DB). A web-based interface for this resource can be freely accessed at http://cbrc.kaust.edu.sa/tcof/ and http://apps.sanbi.ac.za/tcof/. © The Author(s) 2010.

Summary report for IAEA CRP on lifetime prediction for the first wall of a fusion machine (JAERI contribution)

International Nuclear Information System (INIS)

Suzuki, Satoshi; Araki, Masanori; Akiba, Masato

1993-03-01

IAEA Coordinated Research Program (CRP) on 'Lifetime Prediction for the First Wall of a Fusion Machine' was started in 1989. Five participants, Joint Research Centre (JRC-Ispra), The NET team, Kernforschungszentrum Karlsruhe (KfK), Russian Research Center and Japan Atomic Energy Research Institute, contributed in this activity. The purpose of the CRP is to evaluate the thermal fatigue behavior of the first wall of a next generation fusion machine by means of numerical methods and also to contribute the design activities for ITER (International Thermonuclear Experimental Reactor). Thermal fatigue experiments of a first wall mock-up which were carried out in JRC-Ispra were selected as a first benchmark exercise model. All participants performed finite element analyses with various analytical codes to predict the lifetime of the simulated first wall. The first benchmark exercise has successfully been finished in 1992. This report summarizes a JAERI's contribution for this first benchmark exercise. (author)

Mapping Mammalian Cell-type-specific Transcriptional Regulatory Networks Using KD-CAGE and ChIP-seq Data in the TC-YIK Cell Line

Science.gov (United States)

Lizio, Marina; Ishizu, Yuri; Itoh, Masayoshi; Lassmann, Timo; Hasegawa, Akira; Kubosaki, Atsutaka; Severin, Jessica; Kawaji, Hideya; Nakamura, Yukio; Suzuki, Harukazu; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R. R.

2015-01-01

Mammals are composed of hundreds of different cell types with specialized functions. Each of these cellular phenotypes are controlled by different combinations of transcription factors. Using a human non islet cell insulinoma cell line (TC-YIK) which expresses insulin and the majority of known pancreatic beta cell specific genes as an example, we describe a general approach to identify key cell-type-specific transcription factors (TFs) and their direct and indirect targets. By ranking all human TFs by their level of enriched expression in TC-YIK relative to a broad collection of samples (FANTOM5), we confirmed known key regulators of pancreatic function and development. Systematic siRNA mediated perturbation of these TFs followed by qRT-PCR revealed their interconnections with NEUROD1 at the top of the regulation hierarchy and its depletion drastically reducing insulin levels. For 15 of the TF knock-downs (KD), we then used Cap Analysis of Gene Expression (CAGE) to identify thousands of their targets genome-wide (KD-CAGE). The data confirm NEUROD1 as a key positive regulator in the transcriptional regulatory network (TRN), and ISL1, and PROX1 as antagonists. As a complimentary approach we used ChIP-seq on four of these factors to identify NEUROD1, LMX1A, PAX6, and RFX6 binding sites in the human genome. Examining the overlap between genes perturbed in the KD-CAGE experiments and genes with a ChIP-seq peak within 50 kb of their promoter, we identified direct transcriptional targets of these TFs. Integration of KD-CAGE and ChIP-seq data shows that both NEUROD1 and LMX1A work as the main transcriptional activators. In the core TRN (i.e., TF-TF only), NEUROD1 directly transcriptionally activates the pancreatic TFs HSF4, INSM1, MLXIPL, MYT1, NKX6-3, ONECUT2, PAX4, PROX1, RFX6, ST18, DACH1, and SHOX2, while LMX1A directly transcriptionally activates DACH1, SHOX2, PAX6, and PDX1. Analysis of these complementary datasets suggests the need for caution in interpreting Ch

A Simple Reverse Transcription-Polymerase Chain Reaction for Dengue Type 2 Virus Identification

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Luiz Tadeu M Figueiredo

1997-05-01

Full Text Available We show here a simplified reverse transcription-polymerase chain reaction (RT-PCR for identification of dengue type 2 virus. Three dengue type 2 virus strains, isolated from Brazilian patients, and yellow fever vaccine 17DD, as a negative control, were used in this study. C6/36 cells were infected with the virus, and tissue culture fluids were collected after 7 days of infection period. The RT-PCR, a combination of RT and PCR done after a single addition of reagents in a single reaction vessel was carried out following a digestion of virus with 1% Nonidet P-40. The 50ml assay reaction mixture included 50 pmol of a dengue type 2 specific primer pair amplifying a 210 base pair sequence of the envelope protein gene, 0.1 mM of the four deoxynucleoside triphosphates, 7.5U of reverse transcriptase, and 1U of thermostable Taq DNA polymerase. The reagent mixture was incubated for 15 min at 37oC for RT followed by a variable amount of cycles of two-step PCR amplification (92oC for 60 sec, 53oC for 60 sec with slow temperature increment. The PCR products were subjected to 1.7% agarose gel electrophoresis and visualized with UV light after gel incubation in ethidium bromide solution. DNA bands were observed after 25 and 30 cycles of PCR. Virus amount as low as 102.8 TCID50/ml was detected by RT-PCR. Specific DNA amplification was observed with the three dengue type 2 strains. This assay has advantages compared to other RT-PCRs: it avoids laborious extraction of virus RNA; the combination of RT and PCR reduces assay time, facilitates the performance and reduces risk of contamination; the two-step PCR cycle produces a clear DNA amplification, saves assay time and simplifies the technique

A study on the development of a fast neutron television converter

International Nuclear Information System (INIS)

Yoshii, Koji; Miya, Kenzo

1993-01-01

Experiments on fast neutron radiography (FNR) were carried out using the fast neutron source reactor YAYOI of the University of Tokyo. For a real time imaging technique using FNR, for a fast neutron television system (FNR-TV), it is essential to develop a highly sensitive luminescent converter in order to obtain good quality images. A new converter was recently developed and tested. It showed an about six times higher sensitivity compared with the first prototype converter. In this paper, the characteristics of the converter are discussed as well as the clearer images of a FNR-TV when using the converter. The FNR-TV images were obtained with 500 frames integrated. A small hole (1.0 mm in diameter and 10 mm in depth) in an acrylic plate was well imaged through a 50 mm thick iron block. A 0.15 mm thick aluminum spacer in the calibrated fuel pin was also discernible. (orig.)

Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP.

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Wessel M A van Leeuwen

Full Text Available BACKGROUND: Sleep restriction, leading to deprivation of sleep, is common in modern 24-h societies and is associated with the development of health problems including cardiovascular diseases. Our objective was to investigate the immunological effects of prolonged sleep restriction and subsequent recovery sleep, by simulating a working week and following recovery weekend in a laboratory environment. METHODS AND FINDINGS: After 2 baseline nights of 8 hours time in bed (TIB, 13 healthy young men had only 4 hours TIB per night for 5 nights, followed by 2 recovery nights with 8 hours TIB. 6 control subjects had 8 hours TIB per night throughout the experiment. Heart rate, blood pressure, salivary cortisol and serum C-reactive protein (CRP were measured after the baseline (BL, sleep restriction (SR and recovery (REC period. Peripheral blood mononuclear cells (PBMC were collected at these time points, counted and stimulated with PHA. Cell proliferation was analyzed by thymidine incorporation and cytokine production by ELISA and RT-PCR. CRP was increased after SR (145% of BL; p<0.05, and continued to increase after REC (231% of BL; p<0.05. Heart rate was increased after REC (108% of BL; p<0.05. The amount of circulating NK-cells decreased (65% of BL; p<0.005 and the amount of B-cells increased (121% of BL; p<0.005 after SR, but these cell numbers recovered almost completely during REC. Proliferation of stimulated PBMC increased after SR (233% of BL; p<0.05, accompanied by increased production of IL-1beta (137% of BL; p<0.05, IL-6 (163% of BL; p<0.05 and IL-17 (138% of BL; p<0.05 at mRNA level. After REC, IL-17 was still increased at the protein level (119% of BL; p<0.05. CONCLUSIONS: 5 nights of sleep restriction increased lymphocyte activation and the production of proinflammatory cytokines including IL-1beta IL-6 and IL-17; they remained elevated after 2 nights of recovery sleep, accompanied by increased heart rate and serum CRP, 2 important risk

The IAEA co-ordinated research programme on improvement of measurements, theoretical computations and evaluations of neutron induced helium production cross sections. Status report. Prepared at the final CRP meeting in Sendai, Japan 25-29 September 1995

International Nuclear Information System (INIS)

Pashchenko, A.B.

1996-12-01

The present report describes the results of the IAEA Co-ordinated Research Programme (CRP) on ''Improvements of Measurements, Theoretical Computation and Evaluations of Neutron Induced Helium Production Cross Sections''. Summarized is the progress achieved under the CRP in the following areas: measurements of α-production cross sections for structural materials, theoretical computations at (nα) cross sections; measurements of activation cross sections; and improvement of experimental methods for (n,α) investigations. The status report gives also short summaries on the work of each laboratory which contributed to the results of the CRP. Attached is the list of program members and participants of CRP meetings. (author). Refs, 2 figs, 1 tab

Crystal Structure of a Putative HTH-Type Transcriptional Regulator yxaF from Bacillus subtilis

International Nuclear Information System (INIS)

Seetharaman, J.; Kumaran, D.; Bonanno, J.; Burley, S.; Swaminathan, S.

2006-01-01

The New York Structural GenomiX Research Consortium (NYSGXRC) has selected the protein coded by yxaF gene from Bacillus subtilis as a target for structure determination. The yxaF protein has 191 residues with a molecular mass of 21 kDa and had no sequence homology to any structure in the Protein Data Bank (PDB) at the time of target selection. We aimed to elucidate the three-dimensional structure for the putative protein yxaF to better understand the relationship between protein sequence, structure, and function. This protein is annotated as a putative helix-turn-helix (HTH) type transcriptional regulator. Many transcriptional regulators like TetR and QacR use a structurally well-defined DNA-binding HTH motif to recognize the target DNA sequences. DNA-HTH motif interactions have been extensively studied. As the HTH motif is structurally conserved in many regulatory proteins, these DNA-protein complexes show some similarity in DNA recognition patterns. Many such regulatory proteins have a ligand-binding domain in addition to the DNA-binding domain. Structural studies on ligand-binding regulatory proteins provide a wealth of information on ligand-, and possibly drug-, binding mechanisms. Understanding the ligand-binding mechanism may help overcome problems with drug resistance, which represent increasing challenges in medicine. The protein encoded by yxaF, hereafter called T1414, shows fold similar to QacR repressor and TetR/CamR repressor and possesses putative DNA and ligand-binding domains. Here, we report the crystal structure of T1414 and compare it with structurally similar drug and DNA-binding proteins

Analysis of the ArcA regulon in anaerobically grown Salmonella enterica sv. Typhimurium

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Porwollik Steffen

2011-03-01

Full Text Available Abstract Background Salmonella enterica serovar Typhimurium (S. Typhimurium is a Gram-negative pathogen that must successfully adapt to the broad fluctuations in the concentration of dissolved dioxygen encountered in the host. In Escherichia coli, ArcA (Aerobic Respiratory Control helps the cells to sense and respond to the presence of dioxygen. The global role of ArcA in E. coli is well characterized; however, little is known about its role in anaerobically grown S. Typhimurium. Results We compared the transcriptional profiles of the virulent wild-type (WT strain (ATCC 14028s and its isogenic arcA mutant grown under anaerobic conditions. We found that ArcA directly or indirectly regulates 392 genes (8.5% of the genome; of these, 138 genes are poorly characterized. Regulation by ArcA in S. Typhimurium is similar, but distinct from that in E. coli. Thus, genes/operons involved in core metabolic pathways (e.g., succinyl-CoA, fatty acid degradation, cytochrome oxidase complexes, flagellar biosynthesis, motility, and chemotaxis were regulated similarly in the two organisms. However, genes/operons present in both organisms, but regulated differently by ArcA in S. Typhimurium included those coding for ethanolamine utilization, lactate transport and metabolism, and succinate dehydrogenases. Salmonella-specific genes/operons regulated by ArcA included those required for propanediol utilization, flagellar genes (mcpAC, cheV, Gifsy-1 prophage genes, and three SPI-3 genes (mgtBC, slsA, STM3784. In agreement with our microarray data, the arcA mutant was non-motile, lacked flagella, and was as virulent in mice as the WT. Additionally, we identified a set of 120 genes whose regulation was shared with the anaerobic redox regulator, Fnr. Conclusion(s We have identified the ArcA regulon in anaerobically grown S. Typhimurium. Our results demonstrated that in S. Typhimurium, ArcA serves as a transcriptional regulator coordinating cellular metabolism, flagella

Arabidopsis R2R3-MYB transcription factor AtMYB60 functions as a transcriptional repressor of anthocyanin biosynthesis in lettuce (Lactuca sativa).

Science.gov (United States)

Park, Jong-Sug; Kim, Jung-Bong; Cho, Kang-Jin; Cheon, Choong-Ill; Sung, Mi-Kyung; Choung, Myoung-Gun; Roh, Kyung-Hee

2008-06-01

The MYB transcription factors play important roles in the regulation of many secondary metabolites at the transcriptional level. We evaluated the possible roles of the Arabidopsis R2R3-MYB transcription factors in flavonoid biosynthesis because they are induced by UV-B irradiation but their associated phenotypes are largely unexplored. We isolated their genes by RACE-PCR, and performed transgenic approach and metabolite analyses in lettuce (Lactuca sativa). We found that one member of this protein family, AtMYB60, inhibits anthocyanin biosynthesis in the lettuce plant. Wild-type lettuce normally accumulates anthocyanin, predominantly cyanidin and traces of delphinidin, and develops a red pigmentation. However, the production and accumulation of anthocyanin pigments in AtMYB60-overexpressing lettuce was inhibited. Using RT-PCR analysis, we also identified the complete absence or reduction of dihydroflavonol 4-reductase (DFR) transcripts in AtMYB60- overexpressing lettuce (AtMYB60-117 and AtMYB60-112 lines). The correlation between the overexpression of AtMYB60 and the inhibition of anthocyanin accumulation suggests that the transcription factorAtMYB60 controls anthocyanin biosynthesis in the lettuce leaf. Clarification of the roles of the AtMYB60 transcription factor will facilitate further studies and provide genetic tools to better understand the regulation in plants of the genes controlled by the MYB-type transcription factors. Furthermore, the characterization of AtMYB60 has implications for the development of new varieties of lettuce and other commercially important plants with metabolic engineering approaches.

Diagnostic value of procalcitonin, CRP, leukocytes and BAL neutrophils for pulmonary complications in the immunocompromised host

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Daiana Stolz

2006-12-01

Full Text Available We evaluated the diagnostic accuracy of laboratory biomarkers and BAL differential cell count for the diagnosis of bacterial infection in severe immunosuppressed patients. One-hundred and seven consecutive patients undergoing bronchoscopy for suspected pulmonary infection were included in this study. Assessment included history, clinical examination, chest image studies, CRP, procalcitonin (ProCT, leukocyte counts, and BAL results. Patients were classified as having proven, possible, and non-bacterial infection.

Transcription of two adjacent carbohydrate utilization gene clusters in Bifidobacterium breve UCC2003 is controlled by LacI- and repressor open reading frame kinase (ROK)-type regulators.

Science.gov (United States)

O'Connell, Kerry Joan; Motherway, Mary O'Connell; Liedtke, Andrea; Fitzgerald, Gerald F; Paul Ross, R; Stanton, Catherine; Zomer, Aldert; van Sinderen, Douwe

2014-06-01

Members of the genus Bifidobacterium are commonly found in the gastrointestinal tracts of mammals, including humans, where their growth is presumed to be dependent on various diet- and/or host-derived carbohydrates. To understand transcriptional control of bifidobacterial carbohydrate metabolism, we investigated two genetic carbohydrate utilization clusters dedicated to the metabolism of raffinose-type sugars and melezitose. Transcriptomic and gene inactivation approaches revealed that the raffinose utilization system is positively regulated by an activator protein, designated RafR. The gene cluster associated with melezitose metabolism was shown to be subject to direct negative control by a LacI-type transcriptional regulator, designated MelR1, in addition to apparent indirect negative control by means of a second LacI-type regulator, MelR2. In silico analysis, DNA-protein interaction, and primer extension studies revealed the MelR1 and MelR2 operator sequences, each of which is positioned just upstream of or overlapping the correspondingly regulated promoter sequences. Similar analyses identified the RafR binding operator sequence located upstream of the rafB promoter. This study indicates that transcriptional control of gene clusters involved in carbohydrate metabolism in bifidobacteria is subject to conserved regulatory systems, representing either positive or negative control.

Identification of herpes simplex virus type 1 proteins encoded within the first 1.5 kb of the latency-associated transcript.

Science.gov (United States)

Henderson, Gail; Jaber, Tareq; Carpenter, Dale; Wechsler, Steven L; Jones, Clinton

2009-09-01

Expression of the first 1.5 kb of the latency-associated transcript (LAT) that is encoded by herpes simplex virus type 1 (HSV-1) is sufficient for wild-type (wt) levels of reactivation from latency in small animal models. Peptide-specific immunoglobulin G (IgG) was generated against open reading frames (ORFs) that are located within the first 1.5 kb of LAT coding sequences. Cells stably transfected with LAT or trigeminal ganglionic neurons of mice infected with a LAT expressing virus appeared to express the L2 or L8 ORF. Only L2 ORF expression was readily detected in trigeminal ganglionic neurons of latently infected mice.

Changes of serum tumor markers, immunoglobulins, TNF-α and hs-CRP levels in patients with breast cancer and its clinical significance

Institute of Scientific and Technical Information of China (English)

Jian-Gang Dai; Yong-Feng Wu; Mei Li

2017-01-01

Objective: To study the serum tumor markers, immunoglobulin, TNF-α and hs-CRP in breast cancer in different pathological stages of the concentration, and to analyze the clinical significance of early diagnosis of breast cancer. Methods: A total of 130 patients with breast cancer were divided into stage I, II, III and IV according to clinical pathology. In addition, 40 patients with benign breast disease and 35 healthy subjects were selected as benign breast disease group and control group. Serum tumor markers, immunoglobulins, TNF-αand hs-CRP concentrations were measured and compared of all subjects. Results: There were no significant difference in serum tumor markers, immunoglobulin and inflammatory factors between the control group and the benign breast cancer group. The level of serum tumor markers in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum CA125, CA153 and CEA were gradually increased with the severity enhancing from stage I and IV of breast cancer, and he difference was statistically significant. The level of serum immunoglobulin in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum IgG and IgM increased gradually severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. The level of serum TNF-α and hs-CRP in serum of breast cancer group was significantly higher than that of control group and benign breast cancer group. The serum levels of TNF-α and hs-CRP increased gradually with severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. Conclusion: The level of serum tumor markers in breast cancer patients is increasing. Humoral and inflammatory responses are activated to varying degrees and increase with the aggregation of disease. They may involve regulating the occurrence and metastasis of breast

Energy balance and macronutrient distribution in relation to C-reactive protein and HbA1c levels among patients with type 2 diabetes

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Hiba Bawadi

2016-05-01

Full Text Available Background: Recently growing evidence indicates that obesity and diabetes are states of inflammation associated with elevated circulation of inflammatory mediators. Excess adiposity and oxidative stress, induced by feeding, may also lead to a state of low-grade inflammation. Objective: This study aimed at investigating energy balance and distribution in relation to low-grade inflammation among patients with type 2 diabetes. Design: A cross-sectional study included 198 male and female patients with type 2 diabetes. Patients’ weight, height, waist circumference, total body fat and truncal fat percent, energy, and macronutrient intake were measured. Venous blood specimens were collected, and levels of HbA1c and serum levels of high-sensitivity C-reactive protein (hs-CRP were determined. Results: After adjusting for covariates (body mass index, total body fat, and truncal fat, energy balance was positively correlated with hs-CRP and HbA1c. A positive energy balance was also associated with increased waist circumference and truncal fat percent (p<0.05. Total energy intake, percent energy from fat (p=0.04, and percent energy from proteins (p=0.03, but not percent energy from carbohydrates (p=0.12, were also correlated with higher hs-CRP levels among poorly glycemic-controlled patients. Conclusion: Positive energy balance is associated with elevations in hs-CRP. Increased energy intake and increased percentages of energy from fat and protein are associated with elevated hs-CRP among patients with poor glycemic control.