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Sample records for abl-related gene arg

  1. Occurrence and temporal variation of antibiotic resistance genes (ARGs) in shrimp aquaculture: ARGs dissemination from farming source to reared organisms.

    Science.gov (United States)

    Su, Haochang; Liu, Shan; Hu, Xiaojuan; Xu, Xiangrong; Xu, Wujie; Xu, Yu; Li, Zhuojia; Wen, Guoliang; Liu, Yousheng; Cao, Yucheng

    2017-12-31

    Considerable attention has been paid to the occurrence and abundance of antibiotic resistance genes (ARGs) in aquatic environments. However, the temporal variation and dissemination of ARGs in aquaculture environments and reared organisms need further study. This study investigated the abundance and diversity of ARGs and bacterial community in water source, shrimp pond water, sediment, and shrimps during the rearing period in Pearl River Delta region, South China. The results showed that sul1, qnrD, cmlA, and floR were the predominant ARGs in the aquaculture samples. A trend of decreasing abundance of ARGs was observed for pond water samples during the rearing period, whereas an increasing trend was observed in the sediment and shrimp samples. The total concentration of ARGs in water source was significantly higher than that in shrimp pond water (pshrimps were 4.48-19.0 times higher than those in juvenile shrimps. Similar to water source and pond water, cmlA and sul1 were the predominant ARGs in shrimp intestinal tract. The bacterial community in the shrimp intestinal tract changed greatly from juvenile to adult. The results of the present study indicated that the abundances of ARGs in aquaculture varied temporally during the rearing period. Water source was an important medium disseminating ARGs to the aquaculture environments and reared organisms. Sul1 could be used as a potential indicator for ARGs in both water and sediment in aquaculture in the estuary of the Pearl River Delta, South China. This study represents a case study for the temporal variation of abundance and dissemination of ARGs in aquaculture and is a reference for potential risks to food safety and human health. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Polycyclic aromatic hydrocarbons (PAHs) enriching antibiotic resistance genes (ARGs) in the soils.

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    Chen, Baowei; He, Rong; Yuan, Ke; Chen, Enzhong; Lin, Lan; Chen, Xin; Sha, Sha; Zhong, Jianan; Lin, Li; Yang, Lihua; Yang, Ying; Wang, Xiaowei; Zou, Shichun; Luan, Tiangang

    2017-01-01

    The prevalence of antibiotic resistance genes (ARGs) in modern environment raises an emerging global health concern. In this study, soil samples were collected from three sites in petrochemical plant that represented different pollution levels of polycyclic aromatic hydrocarbons (PAHs). Metagenomic profiling of these soils demonstrated that ARGs in the PAHs-contaminated soils were approximately 15 times more abundant than those in the less-contaminated ones, with Proteobacterial being the preponderant phylum. Resistance profile of ARGs in the PAHs-polluted soils was characterized by the dominance of efflux pump-encoding ARGs associated with aromatic antibiotics (e.g., fluoroquinolones and acriflavine) that accounted for more than 70% of the total ARGs, which was significantly different from representative sources of ARG pollution due to wide use of antibiotics. Most of ARGs enriched in the PAHs-contaminated soils were not carried by plasmids, indicating the low possibilities of them being transferred between bacteria. Significant correlation was observed between the total abundance of ARGs and that of Proteobacteria in the soils. Proteobacteria selected by PAHs led to simultaneously enriching of ARGs carried by them in the soils. Our results suggested that PAHs could serve as one of selective stresses for greatly enriching of ARGs in the human-impacted environment.

  3. [Distribution, dissemination and removal of antibiotic resistant genes (ARGs) in the aquatic environment].

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    Wen, Han-qing; Shi, Jun; Xun, Hao; Deng, Hui-ping

    2015-02-01

    In recent years, the intensive use of antibiotics induces the development of antibiotic resistant genes (ARGs), which is an increasingly critical problem affecting human health, and the potential toxic effects of the ARGs have drawn great attention all over the world. This review gave an overview of the occurrence, potential sources, fate and ecological risks of ARGs in the environment. What's more, the removal of ARGs by different treatment processes such as sludge digestion, constructed wetland, disinfection and advanced treatments were assessed, and the improving directions of different treatment processes were also pointed out. Additionally, the highlights in need for further research were proposed based on the current pollution status.

  4. ArgR-dependent repression of arginine and histidine transport genes in Escherichia coli K-12.

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    Caldara, Marina; Minh, Phu Nguyen Le; Bostoen, Sophie; Massant, Jan; Charlier, Daniel

    2007-10-19

    In Escherichia coli L-arginine is taken up by three periplasmic binding protein-dependent transport systems that are encoded by two genetic loci: the artPIQM-artJ and argT-hisJQMP gene clusters. The transcription of the artJ, artPIQM and hisJQMP genes and operons is repressed by liganded ArgR, whereas argT, encoding the LAO (lysine, arginine, ornithine) periplasmic binding protein, is insensitive to the repressor. Here we characterize the repressible Esigma70 P artJ, P artP and P hisJ promoters and demonstrate that the cognate operators consist of two 18 bp ARG boxes separated by 3 bp. Determination of the energy landscape of the ArgR-operator contacts by missing contact probing and mutant studies indicated that each box of a pair contributes to complex formation in vitro and to the repressibility in vivo, but to a different extent. The organization of the ARG boxes and promoter elements in the control regions of the uptake genes is distinct from that of the arginine biosynthetic genes. The hisJQMP operon is the first member of the E. coli ArgR regulon, directly repressed by liganded ArgR, where none of the core promoter elements overlaps the ARG boxes. Single round in vitro transcription assays and DNase I footprinting experiments indicate that liganded ArgR inhibits P artJ and P artP promoter activity by steric exclusion of the RNA polymerase. In contrast, ArgR-mediated repression of P hisJ by inhibition of RNA polymerase binding appears to occur through topological changes of the promoter region.

  5. Sequence diversity within the argF, fbp and recA genes of natural isolates of Neisseria meningitidis: interspecies recombination within the argF gene.

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    Zhou, J; Spratt, B G

    1992-08-01

    Studies of natural populations of Neisseria meningitidis using multilocus enzyme electrophoresis have shown extensive genetic variation within this species, which, it has been proposed, implies a level of sequence diversity within meningococci that is greater than that normally considered as the criterion for species limits in bacteria. To obtain a direct measure of the sequence diversity among meningococci, we obtained the nucleotide sequences of most of the argF, recA and fbp genes of eight meningococci of widely differing electrophoretic type (from the reference collection of Caugant). Sequence variation between the meningococcal strains ranged from 0-0.6% for fbp, 0-1.3% for argF, and 0-3.3% for recA. These levels of diversity are no greater than those found within Escherichia coli 'housekeeping' genes and suggest that multilocus enzyme electrophoresis may overestimate the extent of nucleotide sequence diversity within meningococci. The average sequence divergence between the Neisseria meningitidis strains and N. gonorrhoeae strain FA19 was 1.0% for fbp and 1.6% for recA. The argF gene, although very uniform among the eight meningococcal isolates, had a striking mosaic structure when compared with the gonococcal argF gene: two regions of the gene differed by greater than 13% in nucleotide sequence between meningococci and gonococci, whereas the rest of the gene differed by less than 1.7%. One of the diverged regions was shown to have been introduced from the argF gene of a commensal Neisseria species that is closely related to Neisseria cinerea. The source of the other region was unclear.

  6. Lack of Arg972 polymorphism in the IRS1 gene in Parakand Brazilian Indians

    OpenAIRE

    Bezerra, RMN; Chadid, TT; Altemani, CM; Sales, TSI; Menezes, R.; Soares, MCP; Saad, STO; Saad, MJA

    2004-01-01

    Several polymorphisms in the insulin receptor substrate-1 (IRS1) gene have been reported in the last years. The most common IRS1 variant, a Gly --> Arg substitution at codon 972 (Arg972 IRS1), is more prevalent among subjects who have features of insulin resistance syndrome associated, or not, with type 2 diabetes in European populations. To determine whether the absence of IRS1 polymorphism is a more general characteristic of Paleo-Indian-derived populations, we examined the Arg972 IRS1 poly...

  7. Lack of Arg972 polymorphism in the IRS1 gene in Parakanã Brazilian Indians.

    Science.gov (United States)

    Bezerra, Rosângela M N; Chadid, Thiago T; Altemani, Claúdia M; Sales, Teresa S I; Menezes, Raimundo; Soares, Manoel C P; Saad, Sara T O; Saad, Mario J A

    2004-02-01

    Several polymorphisms in the insulin receptor substrate-1 (IRS1) gene have been reported in the last years. The most common IRS1 variant, a Gly --> Arg substitution at codon 972 (Arg972 IRS1), is more prevalent among subjects who have features of insulin resistance syndrome associated, or not, with type 2 diabetes in European populations. To determine whether the absence of IRS1 polymorphism is a more general characteristic of Paleo-Indian-derived populations, we examined the Arg972 IRS1 polymorphism in Parakanã Indians and found a lack of this polymorphism in the Parakanã population.

  8. [Effects of Thermophilic Composting on Antibiotic Resistance Genes (ARGs) of Swine Manure Source].

    Science.gov (United States)

    Zheng, Ning-guo; Huang, Nan; Wang, Wei-wei; Yu, Man; Chen, Xiao-yang; Yao, Yan-lai; Wang, Wei-ping; Hong, Chun-lai

    2016-05-15

    To investigate the effects of thermophilic composting process on antibiotic resistance genes (ARGs) of swine manure source at a field scale, the abundance of four erythromycin resistance genes (ermA, ermB, ermC and ermF), three β-lactam resistance genes (blaTEM, blaCTX and blaSHV) and two quinolone resistance genes (qnrA and qnrS) were quantified by quantitative PCR ( qPCR) during the composting process. The results suggested that the erm genes' copy numbers were significantly higher than those of the bla and qnr genes in the early stage of composting (P composting process, bla and qnr genes were at low levels, while erm genes were still at high levels. Even through ermF was proliferated comparing with the initial copies. These results indicated that thermophilic composting process could not effectively remove all ARGs. For some ARGs, compost may be a good bioreactor resulting in their proliferation. Application of composting products on farmland may cause transference of ARGs.

  9. Mutation of the Erwinia amylovora argD gene causes arginine auxotrophy, nonpathogenicity in apples, and reduced virulence in pears.

    Science.gov (United States)

    Ramos, Laura S; Lehman, Brian L; Peter, Kari A; McNellis, Timothy W

    2014-11-01

    Fire blight is caused by Erwinia amylovora and is the most destructive bacterial disease of apples and pears worldwide. In this study, we found that E. amylovora argD(1000)::Tn5, an argD Tn5 transposon mutant that has the Tn5 transposon inserted after nucleotide 999 in the argD gene-coding region, was an arginine auxotroph that did not cause fire blight in apple and had reduced virulence in immature pear fruits. The E. amylovora argD gene encodes a predicted N-acetylornithine aminotransferase enzyme, which is involved in the production of the amino acid arginine. A plasmid-borne copy of the wild-type argD gene complemented both the nonpathogenic and the arginine auxotrophic phenotypes of the argD(1000)::Tn5 mutant. However, even when mixed with virulent E. amylovora cells and inoculated onto immature apple fruit, the argD(1000)::Tn5 mutant still failed to grow, while the virulent strain grew and caused disease. Furthermore, the pCR2.1-argD complementation plasmid was stably maintained in the argD(1000)::Tn5 mutant growing in host tissues without any antibiotic selection. Therefore, the pCR2.1-argD complementation plasmid could be useful for the expression of genes, markers, and reporters in E. amylovora growing in planta, without concern about losing the plasmid over time. The ArgD protein cannot be considered an E. amylovora virulence factor because the argD(1000)::Tn5 mutant was auxotrophic and had a primary metabolism defect. Nevertheless, these results are informative about the parasitic nature of the fire blight disease interaction, since they indicate that E. amylovora cannot obtain sufficient arginine from apple and pear fruit tissues or from apple vegetative tissues, either at the beginning of the infection process or after the infection has progressed to an advanced state.

  10. An association between TRP64ARG polymorphism of the B3 adrenoreceptor gene and some metabolic disturbances

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    Abilova Samai S

    2011-10-01

    Full Text Available Abstract Backgrounds B3 adrenoreceptors (ADRB3 are abundant in adipose tissue and play the role in its metabolism and lipolysis. Some variants of the ADRB3 gene may predispose subjects for the development obesity and metabolic abnormalities in the setting of modern sedentary lifestyle. ADRB3 gene polymorphism association with metabolic disturbances has never been studied before in the ethnic Kyrgyz population. Aim To study an association between Trp64Arg polymorphism of the ADRB3 and metabolic syndrome (MS components in an ethnic Kyrgyz group. Materials and methods 213 Ethnic Kyrgyz volunteers over the age of 30 were enrolled in the study. The assessment plan for each individual comprised of general physical and anthropometric exams as well as laboratory tests (glucose, lipid panel, insulin and genotyping by Trp64Arg polymorphism of the ADRB3. MS diagnosis was consistent with modified ATP III criteria (2005. Logistic regression analysis was performed to test the potential independent association between Arg64 allele with obesity, abdominal obesity (AO and arterial hypertension (AH. Results Trp64Arg polymorphism of the ADRB3 was assessed in 213 individuals (145 men, 68 women aged 30-73 (mean age 50.7 ± 7.6. Arg64 allele frequency was 0.239; ADRB3 genotype distribution among participants was: Trp64 homozygotes 54.5%, Trp64Arg 43.2% and Arg64 homozygotes 2.3%. There was an association between Trp64Arg и Arg64Arg genotypes and higher BMI, WC and obesity frequency (p Conclusion Arg64 allele of the ADRB3 gene in the studied group has an association with MS components such as obesity, AO and decreased HDL-C level.

  11. A Strong Promoter Provided with the Gene Encoding Arginyl-tRNA Synthetase(argS) from Escherichia coli.

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    Liu, Mo-Fang; Li, Tong; Yin, Zhao-Bao; Xu, Min-Gang; Wang, En-Duo; Wang, Yin-Lai

    2000-01-01

    Previous studies showed that the gene argS encoding the arginyl-tRNA synthetase(ArgRS) from Escherichia coli(E.coli), was overexpressed 1 000 folds in the E.coli transformant TG1/pUC-argS, while the gene leuS, encoding the leucyl-tRNA synthetase(LeuRS) from E.coli, was only overproduced 35-fold in the same case. To investigate why the expression of these two aminoacyl-tRNA synthetase genes is so different, a fused gene (termed parg-leuS) was constructed by replacement of the 5' flanking region of leuS to 5' flanking region of argS. In the E.coli transformant TG1/pUC-parg-leuS, the activity of LeuRS was only improved 8.5-fold, which was much lower than that of the transformant harboring the recombinant plasmid pUC18-leuS or pKK-leuS. However, by RNA dot hybridization the amount of mRNA produced in the transcription of parg-leuS was about 5 times than that of the wild type leuS, and was similar to that of pKK-leuS, suggesting that the promoter of argS is very strong. Analysis of the secondary structure around the initiation codon among three mRNAs showed that the secondary structure of the mRNA from parg-leuS was the strongest of the three mRNAs. From the results, it could be deduced that expression of the fused gene parg-leuS might be controlled at the translational level and the strong secondary structure of this mRNA may hinder translation initiation and result in a low translation efficiency.

  12. Distribution of antibiotic resistance genes (ARGs) in anaerobic digestion and land application of swine wastewater.

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    Sui, Qianwen; Zhang, Junya; Chen, Meixue; Tong, Juan; Wang, Rui; Wei, Yuansong

    2016-06-01

    Swine farm and the adjacent farmland are hot spots of ARGs. However, few studies have investigated the on-site occurrence of ARGs distributed in the process of anaerobic digestion (AD) followed by land application of swine wastewater. Two typical swine farms, in southern and northern China respectively, with AD along with land application were explored on ARG distributions. ARGs were highly abundant in raw swine wastewater, AD effectively reduced the copy number of all detected ARGs (0.21-1.34 logs removal), but the relative abundance with different resistance mechanisms showed distinctive variation trends. The reduction efficiency of ARGs was improved by stable operational temperature and longer solid retention time (SRT) of AD. ARGs in soil characterized the contamination from the irrigation of the digested liquor. The total ARGs quantity in soil fell down by 1.66 logs in idle period of winter compared to application period of summer in the northern region, whereas the total amount was steady with whole-year application in south. Some persistent (sul1 and sul2) and elevated ARGs (tetG and ereA) in AD and land application need more attention.

  13. Leptin receptor gene Gln223Arg polymorphism is not associated with obesity and metabolic syndrome in Turkish children.

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    Komşu-Ornek, Zuhal; Demirel, Fatma; Dursun, Ahmet; Ermiş, Bahri; Pişkin, Etem; Bideci, Aysun

    2012-01-01

    The aim of the study was to investigate the relationship between leptin receptor gene (LEPR) Gln223Arg polymorphism and obesity in Turkish children. Ninety-two obese and 99 lean children (between 5-15 years) were included in the study. Twenty-three of the obese children were diagnosed with metabolic syndrome. Blood samples were collected for morning fasting blood glucose, insulin, leptin, and lipid level measurements. LEPR Gln223Arg polymorphism was analyzed by restriction fragment length polymorphism. Significant differences were observed in anthropometric measurements, fasting blood glucose, insulin, leptin, and lipid levels between obese and lean children. Serum leptin levels were markedly higher in obese children. No significant association was noted between Gln223Arg polymorphism and serum leptin, insulin and lipid levels. There were no differences in the genotype frequencies or allele distribution for Gln223Arg polymorphism among obese, obese with metabolic syndrome and lean children. Our findings suggest that there is no association between Gln223Arg polymorphism and obesity in Turkish children.

  14. [Regional features of obesity-associated gene polymorphism (rs9939609 FTO gene and gene Trp64Arg ADRB3) in Russian population].

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    Baturin, A K; Sorokina, E Iu; Pogozheva, A V; Peskova, E V; Makurina, O N; Tutel'ian, V A

    2014-01-01

    Recent studies have shown a significant association with obesity polymorphisms: rs9939609 gene due to fat mass and obesity FTO in European and some Asian and African American populations Trp64Arg ADRB3 gene in several European populations. Association of variants rs9939609 and Trp64Arg obesity was studied in 1244 the inhabitants of Moscow and Sverdlovsk regions. Genotyping was performed using allele-specific amplification, detection results in real time using TaqMan-probes complementary DNA polymorphic sites. The frequency of the mutant allele of the FTO gene in the population of Moscow and Sverdlovsk region was 45.1%, with the TT genotype was detected in 30.2% of cases, AT--49.5%, AA--20.3%. Women had the presence of the mutant allele more likely than men (48.4 vs. 42.5%). People with obesity were more genotypes AA (26.3%) and AT (52.8%) compared to the surveyed with a BMI of less than 30 kg/m2 (respectively 18.1 and 50.7%). A significantly higher incidence of risk allele A was found in individuals with obesity (52.6 and 43.4%). The presence of the mutant allele of the gene ADRB3 among the population of Moscow and Sverdlovsk regions was noted in 7.4% of cases. While 15.5% of patients had a heterozygous genotype Trp64Arg ADRB3, that is consistent with international research. The frequency of the risk allele and genotype Arg64 Trp64Arg in women (9.3 and 18.5%) was significantly higher than men (6.2 and 12.2%). The presence of the mutant allele and genotype Trp64Arg ADRB3 (respectively, 9.1 and 18.1%) were significantly more marked in the examined obese compared with those with a body mass index less than 30 kg/m2 (7.4 and 14.9%), but these differences were not statistically significant. The results of these studies suggest that genetic variants of the FTO gene rs9939609 genotype and Trp64Arg ADRB3 contribute to the development of obesity among residents of Moscow and Sverdlovsk Region of Russia. The risk of obesity increases in the case of combined polymorphisms in

  15. Association between TP53 gene Arg72Pro polymorphism and Wilms' tumor risk in a Chinese population.

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    Fu, Wen; Zhuo, Zhen-Jian; Jia, Wei; Zhu, Jinhong; Zhu, Shi-Bo; Lin, Ze-Feng; Wang, Feng-Hua; Xia, Huimin; He, Jing; Liu, Guo-Chang

    2017-01-01

    Wilms' tumor is one of the most prevalent pediatric malignancies, ranking fourth in childhood cancer worldwide. TP53 is a critical tumor suppressor gene, which encodes a 53 kDa protein, p53. The p53 functions to protect against cancer by regulating cell cycle and apoptosis and maintaining DNA integrity. TP53 gene is highly polymorphic. Several TP53 gene polymorphisms have been considered to be associated with cancer risk. Of them, a nonsynonymous polymorphism, Arg72Pro (rs1042522 C>G), has been most extensively studied for the association with cancer risk; however, few studies have investigated its effect on Wilms' tumor. Because of the central role of p53 in cell cycle control, the TP53 gene Arg72Pro polymorphism is also a good potential candidate predisposition locus for this pediatric cancer. We genotyped this polymorphism in 145 patients and 531 cancer-free controls recruited from Chinese children by Taqman methodology. Overall, our result suggested a lack of association between the TP53 gene Arg72Pro polymorphism and Wilms' tumor. In the stratified analysis, we found that carriers of CG/GG genotypes had a significantly increased Wilms' tumor risk in children not older than 18 months (adjusted odds ratio =2.04, 95% confidence interval =1.003-4.13, P=0.049) compared with CC genotype carriers. Our study indicated that the TP53 gene Arg72Pro polymorphism may have a weak, age-related effect on Wilms' tumor risk in Chinese children. These findings need further validations in other populations with larger sample size.

  16. Association between TP53 gene Arg72Pro polymorphism and Wilms’ tumor risk in a Chinese population

    Science.gov (United States)

    Fu, Wen; Zhuo, Zhen-Jian; Jia, Wei; Zhu, Jinhong; Zhu, Shi-Bo; Lin, Ze-Feng; Wang, Feng-Hua; Xia, Huimin; He, Jing; Liu, Guo-Chang

    2017-01-01

    Wilms’ tumor is one of the most prevalent pediatric malignancies, ranking fourth in childhood cancer worldwide. TP53 is a critical tumor suppressor gene, which encodes a 53 kDa protein, p53. The p53 functions to protect against cancer by regulating cell cycle and apoptosis and maintaining DNA integrity. TP53 gene is highly polymorphic. Several TP53 gene polymorphisms have been considered to be associated with cancer risk. Of them, a nonsynonymous polymorphism, Arg72Pro (rs1042522 C>G), has been most extensively studied for the association with cancer risk; however, few studies have investigated its effect on Wilms’ tumor. Because of the central role of p53 in cell cycle control, the TP53 gene Arg72Pro polymorphism is also a good potential candidate predisposition locus for this pediatric cancer. We genotyped this polymorphism in 145 patients and 531 cancer-free controls recruited from Chinese children by Taqman methodology. Overall, our result suggested a lack of association between the TP53 gene Arg72Pro polymorphism and Wilms’ tumor. In the stratified analysis, we found that carriers of CG/GG genotypes had a significantly increased Wilms’ tumor risk in children not older than 18 months (adjusted odds ratio =2.04, 95% confidence interval =1.003–4.13, P=0.049) compared with CC genotype carriers. Our study indicated that the TP53 gene Arg72Pro polymorphism may have a weak, age-related effect on Wilms’ tumor risk in Chinese children. These findings need further validations in other populations with larger sample size. PMID:28260929

  17. Effects of Arc/Arg3.1 gene deletion on rhythmic synchronization of hippocampal CA1 neurons during locomotor activity and sleep.

    NARCIS (Netherlands)

    Malkki, H.A.I.; Mertens, P.E.C.; Lankelma, J.V.; Vinck, M.; van Schalkwijk, F.J.; van Mourik-Donga, L.B.; Battaglia, F.P.; Mahlke, C.; Kuhl, D.; Pennartz, C.M.A.

    2016-01-01

    The activity-regulated cytoskeletal-associated protein/activity regulated gene (Arc/Arg3.1) is crucial for long-term synaptic plasticity and memory formation. However, the neurophysiological substrates of memory deficits occurring in the absence of Arc/Arg3.1 are unknown. We compared hippocampal CA1

  18. Effects of Arc/Arg3.1 gene deletion on rhythmic synchronization of hippocampal CA1 neurons during locomotor activity and sleep.

    NARCIS (Netherlands)

    Malkki, H.A.I.; Mertens, P.E.C.; Lankelma, J.V.; Vinck, M.; van Schalkwijk, F.J.; van Mourik-Donga, L.B.; Battaglia, F.P.; Mahlke, C.; Kuhl, D.; Pennartz, C.M.A.

    2016-01-01

    The activity-regulated cytoskeletal-associated protein/activity regulated gene (Arc/Arg3.1) is crucial for long-term synaptic plasticity and memory formation. However, the neurophysiological substrates of memory deficits occurring in the absence of Arc/Arg3.1 are unknown. We compared hippocampal CA1

  19. Expression of the gene for resistance to phaseolotoxin (argK depends on the activity of genes phtABC in Pseudomonas syringae pv. phaseolicola.

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    Selene Aguilera

    Full Text Available The bacterium Pseudomonas syringae pv. phaseolicola produces phaseolotoxin in a temperature dependent manner, being optimally produced between 18°C and 20°C, while no detectable amounts are present above 28°C. Phaseolotoxin is an effective inhibitor of ornithine carbamoyltransferase (OCTase activity from plant, mammalian and bacterial sources and causes a phenotypic requirement for arginine. To protect the cell from its own toxin, P. syringae pv. phaseolicola synthesizes a phaseolotoxin-resistant OCTase (ROCT. The ROCT is the product of the argK gene and is synthesized only under conditions leading to phaseolotoxin synthesis. The argK gene is included in a chromosomal fragment named Pht cluster, which contains genes involved in the synthesis of phaseolotoxin. The aim of the present work was to investigate the possible involvement of other genes included in the Pht cluster in the regulation of gene argK. We conducted transcriptional analyses of argK in several mutants unable to produce phaseolotoxin, transcriptional fusions and electrophoretic mobility shift assays, which allowed us to determine that genes phtABC, located within the Pht cluster, participate in the transcriptional repression of gene argK at temperatures not permissive for phaseolotoxin biosynthesis. This repression is mediated by a protein present in both toxigenic and nontoxigenic strains of P. syringae and in E. coli, and requires the coordinated participation of phtA, phtB and phtC products in order to carry out an efficient argK repression.

  20. The Polymorphism of DNA Repair Gene ERCC2/XPD Arg156Arg and Susceptibility to Breast Cancer in a Chinese Population

    DEFF Research Database (Denmark)

    Yin, J. Y.; Liang, D. H.; Vogel, Ulla Birgitte

    2009-01-01

    found between ERCC2/XPD Arg156Arg and risk of breast cancer (AA/AC versus CC: OR = 0.79, 95% CI = 0.49-1.28, P = 0.33; AA versus CC: OR = 0.89, 95% CI = 0.49-1.63, P = 0.72; AC versus CC: OR = 0.74, 95% CI = 0.44-1.24, P = 0.25). Breast cancer cases with the variant AA genotype were marginally younger...... the association between ERCC2/XPD Arg156Arg and susceptibility to breast cancer in a Chinese population, we conducted a hospital-based case-control study consisting of 129 patients with breast cancer and 205 controls matched by age, gender, and ethnicity. PCR-RFLP was used for genotyping. No associations were...... (mean age 45 years) than cases with the wild CC genotype (mean age 50 years) (P = 0.05). There were no differences in risk estimates in relation to menopause and occurrence of breast cancer. Our findings do not suggest that ERCC2/XPD Arg156Arg contributes to breast cancer susceptibility in a Chinese...

  1. The Polymorphisms of Ser49Gly and Gly389Arg in Beta-1-Adrenergic Receptor Gene in Major Depression

    Science.gov (United States)

    KOKUT, Süleyman; ATAY, İnci Meltem; UZ, Efkan; AKPINAR, Abdullah; DEMİRDAŞ, Arif

    2015-01-01

    Introduction It was reported that the genetic susceptibility of major depressive disorder (MDD) is related with genetic polymorphisms. The aim of this study was to investigate the possible association of the genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphisms in MDD by comparing them with healthy subjects. Methods A total of 144 patients with MDD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria and 105 healthy controls were included in the study. Polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP) was used for genotyping. Results Of the 144 participants in the MDD group, 77 (53.5%) had homozygous wild type (AA), 57 (39.6%) had heterozygous type (AG), and 10 (6.9%) had mutant (GG) genotype for Ser49Gly, whereas 75 (52.1%) had homozygous wild type (GG), 59 (41.0%) had heterozygous (GC) type, and 10 (6.9%) had mutant homozygous (CC) genotype for Gly386Arg. There were no significant difference in the allele and genotype frequencies of the beta-1-adrenergic receptor (ADRB1) gene for Ser49Gly and Arg389Gly polymorphisms after comparing with healthy controls (p=0.626; p=0.863 and p=0.625; p=0.914). Conclusion The results of our study did not reveal a major effect of the polymorphism of Ser49Gly and Gly389Arg in the ADRB1 gene in MDD. Further studies with larger sample size are required to elucidate the role of other beta-1 adrenergic gene polymorphisms in MDD.

  2. Association between TP53 gene Arg72Pro polymorphism and Wilms’ tumor risk in a Chinese population

    Directory of Open Access Journals (Sweden)

    Fu W

    2017-02-01

    Full Text Available Wen Fu,1,2,* Zhen-Jian Zhuo,3,* Wei Jia,1,2 Jinhong Zhu,4 Shi-Bo Zhu,1,2 Ze-Feng Lin,1,2 Feng-Hua Wang,1,2 Huimin Xia,1,2 Jing He,1,2 Guo-Chang Liu1,2 1Department of Pediatric Urology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 2Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 3Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, 4Molecular Epidemiology Laboratory, Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Wilms’ tumor is one of the most prevalent pediatric malignancies, ranking fourth in childhood cancer worldwide. TP53 is a critical tumor suppressor gene, which encodes a 53 kDa protein, p53. The p53 functions to protect against cancer by regulating cell cycle and apoptosis and maintaining DNA integrity. TP53 gene is highly polymorphic. Several TP53 gene polymorphisms have been considered to be associated with cancer risk. Of them, a nonsynonymous polymorphism, Arg72Pro (rs1042522 C>G, has been most extensively studied for the association with cancer risk; however, few studies have investigated its effect on Wilms’ tumor. Because of the central role of p53 in cell cycle control, the TP53 gene Arg72Pro polymorphism is also a good potential candidate predisposition locus for this pediatric cancer. We genotyped this polymorphism in 145 patients and 531 cancer-free controls recruited from Chinese children by Taqman methodology. Overall, our result suggested a lack of association between the TP53 gene Arg72Pro polymorphism and Wilms’ tumor. In the stratified analysis, we found that carriers of CG/GG genotypes had a significantly increased Wilms’ tumor risk in children not older

  3. Differential coupling of Arg- and Gly389 polymorphic forms of the β1-adrenergic receptor leads to pathogenic cardiac gene regulatory programs

    OpenAIRE

    2008-01-01

    The β1-adrenergic receptor (β1AR; ADRB1) polymorphism Arg389Gly is located in an intracellular loop and is associated with distinct human and mouse cardiovascular phenotypes. To test the hypothesis that β1-Arg389 and β1-Gly389 alleles could differentially couple to pathways beyond that of classic Gs-adenylyl cyclase (AC)/cAMP signaling, we performed comparative gene expression profile analyses on hearts from wild-type and transgenic mice that expressed either human β1-Arg389 or β1-Gly389 rece...

  4. Energy expenditure, body composition and insulin response to glucose in male twins discordant for the Trp64Arg polymorphism of the beta3-adrenergic receptor gene

    DEFF Research Database (Denmark)

    Højlund, K; Christiansen, C; Bjørnsbo, K S;

    2006-01-01

    and environmental background, the Trp64Arg polymorphism of the beta3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.......AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin......-ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry. RESULTS: Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild...

  5. Congenital erythropoietic porphyria with two mutations of the uroporphyrinogen III synthase gene (Cys73Arg, Thr228Met).

    Science.gov (United States)

    Gucev, Zoran; Slavevska, Nevenka; Tasic, Velibor; Laban, Nevenka; Pop-Jordanova, Nada; Danilovski, Dragan; Woolf, Jacqueline; Cole, Duncan

    2011-05-01

    Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase (UROS). We describe a 14-year-old girl with red urine since infancy, progressive blistering and scarring of the skin, and moderate hemolytic anemia. After years of skin damage, her face is mutilated; she has a bald patch on the scalp, hypertrichosis of the neck, areas of skin darkening, and limited joint movements of the hands. Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. Sequencing of the UROS gene identified two mutations causing CEP (Cys73Arg, Thr228Met). The patient lesions are progressing. Bone marrow transplantation and/or gene therapy are proposed as the next steps in her treatment. In brief, we describe a CEP with confirmed two pathogenic mutations, severe phenotype and discuss the various treatment options available.

  6. Congenital erythropoietic porphyria with two mutations of the uroporphyrinogen III synthase gene (Cys73Arg, Thr228Met

    Directory of Open Access Journals (Sweden)

    Zoran Gucev

    2011-01-01

    Full Text Available Congenital erythropoietic porphyria (CEP is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of uroporphyrinogen III synthase (UROS. We describe a 14-year-old girl with red urine since infancy, progressive blistering and scarring of the skin, and moderate hemolytic anemia. After years of skin damage, her face is mutilated; she has a bald patch on the scalp, hypertrichosis of the neck, areas of skin darkening, and limited joint movements of the hands. Total urine excretion and fecal total porphyrin were both markedly raised above normal levels. Sequencing of the UROS gene identified two mutations causing CEP (Cys73Arg, Thr228Met. The patient lesions are progressing. Bone marrow transplantation and/or gene therapy are proposed as the next steps in her treatment. In brief, we describe a CEP with confirmed two pathogenic mutations, severe phenotype and discuss the various treatment options available.

  7. Development and dissection of diagnostic SNP markers for the downy mildew resistance genes PlArg and Pl8 and maker-assisted gene pyramiding in sunflower (Helianthus annuus L.)

    Science.gov (United States)

    Downy mildew, which is caused by fungus Plasmopara halstedii (Farl.) Berlese & de Toni, is one of the most important diseases that affect sunflower production globally. Two downy mildew resistance genes, PlArg and Pl8, were discovered in the late 1980s. Over two decades, PlArg is still effective aga...

  8. p.Pro4Arg mutation in LMNA gene: a new atypical progeria phenotype without metabolism abnormalities.

    Science.gov (United States)

    Guo, Hong; Luo, Na; Hao, Fei; Bai, Yun

    2014-08-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a typical presenile disorder, with mutation in the LMNA gene. Besides HGPS, mutations in LMNA gene have also been reported in atypical progeroid syndrome (APS). The objective of the study was to investigate the phenotype and molecular basis of APS in a Chinese family. LMNA gene mutations were also reviewed to identify the phenotypic and pathogenic differences among APS. Two siblings in a non-consanguineous Chinese family with atypical progeria were reported. The clinical features were observed, including presenile manifestations such as bird-like facial appearance, generalized lipodystrophy involving the extremities and mottled hyperpigmentation on the trunk and extremities. A heterozygous mutation c.11C>G (p.Pro4Arg) of the LMNA gene was detected in the two patients. 28 different variants of the LMNA gene have been reported in APS families, spreading over almost all the 12 exons of the LMNA gene with some hot-spot regions. This is the first detailed description of an APS family without metabolism abnormalities. APS patients share most of the clinical features, but there may be some distinct features in different ethnic groups.

  9. Gene encoding γ-carbonic anhydrase is cotranscribed with argC and induced in response to stationary phase and high CO2 in Azospirillum brasilense Sp7

    Directory of Open Access Journals (Sweden)

    Mishra Mukti N

    2010-07-01

    Full Text Available Abstract Background Carbonic anhydrase (CA is a ubiquitous enzyme catalyzing the reversible hydration of CO2 to bicarbonate, a reaction underlying diverse biochemical and physiological processes. Gamma class carbonic anhydrases (γ-CAs are widespread in prokaryotes but their physiological roles remain elusive. At present, only γ-CA of Methanosarcina thermophila (Cam has been shown to have CA activity. Genome analysis of a rhizobacterium Azospirillum brasilense, revealed occurrence of ORFs encoding one β-CA and two γ-CAs. Results One of the putative γ-CA encoding genes of A. brasilense was cloned and overexpressed in E. coli. Electrometric assays for CA activity of the whole cell extracts overexpressing recombinant GCA1 did not show CO2 hydration activity. Reverse transcription-PCR analysis indicated that gca1 in A. brasilense is co-transcribed with its upstream gene annotated as argC, which encodes a putative N-acetyl-γ-glutamate-phosphate reductase. 5'-RACE also demonstrated that there was no transcription start site between argC and gca1, and the transcription start site located upstream of argC transcribed both the genes (argC-gca1. Using transcriptional fusions of argC-gca1 upstream region with promoterless lacZ, we further demonstrated that gca1 upstream region did not have any promoter and its transcription occurred from a promoter located in the argC upstream region. The transcription of argC-gca1 operon was upregulated in stationary phase and at elevated CO2 atmosphere. Conclusions This study shows lack of CO2 hydration activity in a recombinant protein expressed from a gene predicted to encode a γ-carbonic anhydrase in A. brasilense although it cross reacts with anti-Cam antibody raised against a well characterized γ-CA. The organization and regulation of this gene along with the putative argC gene suggests its involvement in arginine biosynthetic pathway instead of the predicted CO2 hydration.

  10. Methylation of Gata3 protein at Arg-261 regulates transactivation of the Il5 gene in T helper 2 cells.

    Science.gov (United States)

    Hosokawa, Hiroyuki; Kato, Miki; Tohyama, Hiroyuki; Tamaki, Yuuki; Endo, Yusuke; Kimura, Motoko Y; Tumes, Damon John; Motohashi, Shinichiro; Matsumoto, Masaki; Nakayama, Keiichi I; Tanaka, Tomoaki; Nakayama, Toshinori

    2015-05-22

    Gata3 acts as a master regulator for T helper 2 (Th2) cell differentiation by inducing chromatin remodeling of the Th2 cytokine loci, accelerating Th2 cell proliferation, and repressing Th1 cell differentiation. Gata3 also directly transactivates the interleukin-5 (Il5) gene via additional mechanisms that have not been fully elucidated. We herein identified a mechanism whereby the methylation of Gata3 at Arg-261 regulates the transcriptional activation of the Il5 gene in Th2 cells. Although the methylation-mimicking Gata3 mutant retained the ability to induce IL-4 and repress IFNγ production, the IL-5 production was selectively impaired. We also demonstrated that heat shock protein (Hsp) 60 strongly associates with the methylation-mimicking Gata3 mutant and negatively regulates elongation of the Il5 transcript by RNA polymerase II. Thus, arginine methylation appears to play a pivotal role in the organization of Gata3 complexes and the target gene specificity of Gata3.

  11. Antithrombin gene Arg197Stop mutation-associated venous sinus thrombosis in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    Ang Li; Dexin Wang; Qiming Xue; Baoen Wang; Tianhui Liu; Zhandong Liu; Jimei Li; Chunling Zhang; Jun Chen; Jinmei Sun; YanfeiHan; Lili Wang

    2011-01-01

    This study sought to elucidate the genetic correlation of cerebral venous sinus thrombosis caused by a hereditary antithrombin deficiency in a Chinese family, at the genetic and protein levels. A nonsense mutation from C to T on locus 6431 in exon 3B of the antithrombin gene was observed,leading to an arginine (CGA) to stop codon (TGA) change in the protein. This is the first report of this mutation in China. Ineffective heparin therapy in the propositus patient is associated with a lack of heparin binding sites after antithrombin gene mutation. Characteristic low intracranial pressure in the acute phase might be specific to this patient with cerebral venous sinus thrombosis.

  12. Relationship between Trp64Arg mutation in the β3-adrenergic receptor gene and metabolic syndrome: a seven-year follow-up study

    Institute of Scientific and Technical Information of China (English)

    ZHU Lü-yun; HU Li-ye; LI Xiao-ling; WANG Guang-yu; SHAN Wei; MA Li-cheng; WANG Xiu-hui

    2010-01-01

    Background It has been shown that the β3-adrenergic receptor (β3-AR) gene Trp64Arg mutation was closely related to obesity and insulin resistance, and may be related to the prevalence of metabolic syndrome (MS). The aim of this study was to investigate the relationship between the 33-AR gene mutation and the prevalence of MS. Methods A seven-year follow-up study was initiated in 2000, with 496 samples of simplex obese subjects (body mass index ≥25 kg/m2) and 248 normal-weight subjects. According to the β3-AR genotypes, the subjects were classified as Trp64 homozygote group and Arg64 carrier group and after 7 years the prevalence of MS was determined. Results According to the baseline profile, there were no significant differences in the adiposity, blood pressure, lipid profile, fasting plasma glucose and fasting insulin between Trp64 homozygote group and Arg64 carrier group either in obesity or normal-weight subjects. The results of follow-up study indicated that in obese men the prevalence rate of MS was much higher in Arg64 carrier group than that in Trp64 homozygote group (54.76% vs. 40.85%, P <0.05), but there was no statistical difference in women of the above groups. The prevalence rate of MS in obese men of both Trp64 homozygote group and Arg64 carrier obese group were obviously higher than that in women of the above groups (40.85% vs. 18.27% and 54.76% vs 21.28%, all P <0.005). Differences were not statistically significant in the prevalence of MS for normal weight Trp64 homozygote group and normal weight Arg64 carrier group, either between men, between women, or between men and women. Comparison of populations indicated that no matter with the β3-AR gene mutation or not, the prevalence of MS in obese subjects was significantly higher than normal weight subjects (X2=28.240 and x2=15.586, all P <0.005). Logistic analysis showed that the mutation of β3-AR gene was associated with the prevalence of MS in men.

  13. Development and dissection of diagnostic SNP markers for the downy mildew resistance genes Pl Arg and Pl 8 and maker-assisted gene pyramiding in sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Qi, L L; Talukder, Z I; Hulke, B S; Foley, M E

    2017-02-03

    Diagnostic DNA markers are an invaluable resource in breeding programs for successful introgression and pyramiding of disease resistance genes. Resistance to downy mildew (DM) disease in sunflower is mediated by Pl genes which are known to be effective against the causal fungus, Plasmopara halstedii. Two DM resistance genes, Pl Arg and Pl 8 , are highly effective against P. halstedii races in the USA, and have been previously mapped to the sunflower linkage groups (LGs) 1 and 13, respectively, using simple sequence repeat (SSR) markers. In this study, we developed high-density single nucleotide polymorphism (SNP) maps encompassing the Pl arg and Pl 8 genes and identified diagnostic SNP markers closely linked to these genes. The specificity of the diagnostic markers was validated in a highly diverse panel of 548 sunflower lines. Dissection of a large marker cluster co-segregated with Pl Arg revealed that the closest SNP markers NSA_007595 and NSA_001835 delimited Pl Arg to an interval of 2.83 Mb on the LG1 physical map. The SNP markers SFW01497 and SFW06597 delimited Pl 8 to an interval of 2.85 Mb on the LG13 physical map. We also developed sunflower lines with homozygous, three gene pyramids carrying Pl Arg , Pl 8 , and the sunflower rust resistance gene R 12 using the linked SNP markers from a segregating F2 population of RHA 340 (carrying Pl 8 )/RHA 464 (carrying Pl Arg and R 12 ). The high-throughput diagnostic SNP markers developed in this study will facilitate marker-assisted selection breeding, and the pyramided sunflower lines will provide durable resistance to downy mildew and rust diseases.

  14. [Polymorphic markers Ala455Val of the THBD gene and Arg353Gln of the F7 gene and association with unfavorable outcomes of coronary atherosclerosis in patients with a history of acute ischemic heart disease].

    Science.gov (United States)

    Pushkov, A A; Blagodatskikh, K A; Nikitin, A G; Agapkina, Iu V; Brovkin, A N; Chudakova, D A; Evdokimova, M A; Aseĭcheva, O Iu; Osmolovskaia, V S; Minushkina, L O; Baklanova, T N; Talyzin, P A; Donetskaia, O P; Tereshchenko, S N; Dzhaiani, N A; Akatova, E A; Glezer, M G; Galiavich, A S; Zakirova, V B; Koziolova, N A; Iagoda, A V; Boeva, O I; Horolets, E V; Shlyk, S V; Volkova, E G; Margarian, M P; Guz', I O; Konstantinov, V O; Sidorenko, B A; Zateĭshchikov, D A; Nosikov, V V

    2011-10-01

    The polymorphic markers Ala455Val of the THBD gene and Arg353Gln of the F7 gene were tested for association with the frequency of unfavorable outcomes in patients with a history of acute ischemic heart disease. The study involved 1145 patients hospitalized in cardiology clinics of Moscow, St. Petersburg, Kazan, Chelyabinsk, Perm, Stavropol, and Rostov-on-Don because of acute ischemic heart disease. The patients were followed up for up to 62.5 months. None of the markers displayed a significant association with the time to an endpoint. The patients were then grouped by sex. In females, the frequency of unfavorable outcomes (fatal or nonfatal myocardial infarction and fatal or nonfatal stroke) was higher in carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and carriers of genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene, but the difference was not statistically significant. Such an increase in frequency was not observed in males. To study the combined effect of the polymorphic markers of the THBD and F7 genes, the course of ischemic heart disease was compared for two female subgroups. One included carriers of allele Val of the Ala344Val polymorphic marker of the THBD gene and genotype Arg/Arg of the Arg353Gln polymorphic marker of the F7 gene; the other subgroup included carriers ofgenotype Ala/Ala of the Ala455Val polymorphic marker of the THBD gene and allele Gln of the Arg353Gln polymorphic marker of the F7 gene. The frequency of unfavorable outcomes in the first subgroup was higher than in the second one. The time to an endpoin was 40.5 months (95% confidence interval (CI) 33.5-47.6) in the first subgroup and 51.6 months (95% CI 45.0-58.1) in the second subgroup (chi2 = 4.15, P = 0.042). The results made it possible to assume that the F7 and THBD genes play an important role in genetic predisposition to unfavorable outcomes in patients with a history of acute ischemic heart disease.

  15. Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance.

    Science.gov (United States)

    Takagi, Yuki; Murata, Moe; Kozuka, Toshihiro; Nakata, Yukiko; Hasebe, Ryo; Tamura, Shogo; Takagi, Akira; Matsushita, Tadashi; Saito, Hidehiko; Kojima, Tetsuhito

    2016-11-30

    Antithrombin (AT) and thrombomodulin (TM) play important roles in the process of natural anticoagulation in vivo. Recently, we reported that the prothrombin Yukuhashi mutation (p.Arg596Leu) was associated with AT and TM resistance-related thrombophilia. To assess the AT and TM resistances associated with other missense mutations by single base substitution in the Arg596 codon, we generated recombinant variants (596Gln, 596Trp, 596Gly, and 596Pro) and investigated the effects on AT and TM anticoagulant functions. All variants except 596Pro were secreted in amounts comparable to that of the wild-type but exhibited variable procoagulant activities. After a 30-minute inactivation by AT, the relative residual activity of wild-type thrombin decreased to 15 ± 4.0 %, in contrast to values of all variants were maintained at above 80 %. The thrombin-AT complex formation, as determined by enzyme-linked immunosorbent assay, was reduced with all tested variants in the presence and absence of heparin. In the presence of soluble TM (sTM), the relative fibrinogen clotting activity of wild-type thrombin decreased to 16 ± 0.12 %, whereas that of tested variants was 37 %-56 %. In a surface plasmon resonance assay, missense Arg596 mutations reduced thrombin-TM affinity to an extent similar to the reduction of fibrinogen clotting inhibition. In the presence of sTM or cultured endothelial-like cells, APC generation was enhanced differently by variant thrombins in a thrombin-TM affinity-dependent manner. These data indicate that prothrombin Arg596 missense mutations lead to AT and TM resistance in the variant thrombins and suggest that prothrombin Arg596 is important for AT- and TM-mediated anticoagulation.

  16. Fibroblast growth factor receptor 4 gene (FGFR4) 388Arg allele predicts prolonged survival and platinum sensitivity in advanced ovarian cancer.

    Science.gov (United States)

    Marmé, Frederik; Hielscher, Thomas; Hug, Sarah; Bondong, Sandra; Zeillinger, Robert; Castillo-Tong, Dan Cacsire; Sehouli, Jalid; Braicu, Ioana; Vergote, Ignace; Isabella, Cadron; Mahner, Sven; Ferschke, Irmgard; Rom, Joachim; Sohn, Christof; Schneeweiss, Andreas; Altevogt, Peter

    2012-08-15

    FGFR4 has been shown to play an important role in the etiology and progression of solid tumors. A single nucleotide polymorphism (SNP) within the FGFR4 gene has previously been linked to prognosis and response to chemotherapy in breast cancer and other malignancies. This study evaluates the relevance of this SNP in advanced ovarian cancer. FGFR4-genotype was analyzed in 236 patients recruited as part of the OVCAD project. Genotyping was performed on germ-line DNA using a TaqMan based genotyping assay. Results were correlated with clinicopathological variables and survival. The FGFR4 388Arg genotype was significantly associated with prolonged progression-free and overall survival (univariate: HR 0.68, p = 0.017; HR 0.49, p = 0.005; multivariate: HR 0.69, p = 0.025; HR 0.49, p = 0.006) though the positive prognostic value was restricted to patients without postoperative residual tumor. Indeed, there was a significant interaction between FGFR4 genotype and residual tumor for overall survival. Furthermore, the FGFR4 388Arg genotype significantly correlated with platinum sensitivity in the same subgroup (multivariate OR 3.81 p = 0.004). FGFR4 Arg388Gly genotype is an independent and strong context specific prognostic factor in patients with advanced ovarian cancer and could be used to predict platinum-sensitivity.

  17. Effects of Arc/Arg3.1 gene deletion on rhythmic synchronization of hippocampal CA1 neurons during locomotor activity and sleep.

    Science.gov (United States)

    Malkki, Hemi A I; Mertens, Paul E C; Lankelma, Jan V; Vinck, Martin; van Schalkwijk, Frank J; van Mourik-Donga, Laura B; Battaglia, Francesco P; Mahlke, Claudia; Kuhl, Dietmar; Pennartz, Cyriel M A

    2016-05-01

    The activity-regulated cytoskeletal-associated protein/activity regulated gene (Arc/Arg3.1) is crucial for long-term synaptic plasticity and memory formation. However, the neurophysiological substrates of memory deficits occurring in the absence of Arc/Arg3.1 are unknown. We compared hippocampal CA1 single-unit and local field potential (LFP) activity in Arc/Arg3.1 knockout and wild-type mice during track running and flanking sleep periods. Locomotor activity, basic firing and spatial coding properties of CA1 cells in knockout mice were not different from wild-type mice. During active behavior, however, knockout animals showed a significantly shifted balance in LFP power, with a relative loss in high-frequency (beta-2 and gamma) bands compared to low-frequency bands. Moreover, during track-running, knockout mice showed a decrease in phase locking of spiking activity to LFP oscillations in theta, beta and gamma bands. Sleep architecture in knockout mice was not grossly abnormal. Sharp-wave ripples, which have been associated with memory consolidation and replay, showed only minor differences in dynamics and amplitude. Altogether, these findings suggest that Arc/Arg3.1 effects on memory formation are not only manifested at the level of molecular pathways regulating synaptic plasticity, but also at the systems level. The disrupted power balance in theta, beta and gamma rhythmicity and concomitant loss of spike-field phase locking may affect memory encoding during initial storage and memory consolidation stages.

  18. No association of the neuropeptide Y (Leu7Pro) and ghrelin gene (Arg51Gln, Leu72Met, Gln90Leu) single nucleotide polymorphisms with eating disorders.

    Science.gov (United States)

    Kindler, Jochen; Bailer, Ursula; de Zwaan, Martina; Fuchs, Karoline; Leisch, Friedrich; Grün, Bettina; Strnad, Alexandra; Stojanovic, Mirjana; Windisch, Julia; Lennkh-Wolfsberg, Claudia; El-Giamal, Nadja; Sieghart, Werner; Kasper, Siegfried; Aschauer, Harald

    2011-06-01

    Genetic factors likely contribute to the biological vulnerability of eating disorders. Case-control association study on one neuropeptide Y gene (Leu7Pro) polymorphism and three ghrelin gene (Arg51Gln, Leu72Met and Gln90Leu) polymorphisms. 114 eating disorder patients (46 with anorexia nervosa, 30 with bulimia nervosa, 38 with binge eating disorder) and 164 healthy controls were genotyped. No differences were detected between patients and controls for any of the four polymorphisms in allele frequency and genotype distribution (P > 0.05). Allele frequencies and genotypes had no significant influence on body mass index (P > 0.05) in eating disorder patients. Positive findings of former case-control studies of associations between ghrelin gene polymorphisms and eating disorders could not be replicated. Neuropeptide Y gene polymorphisms have not been investigated in eating disorders before.

  19. Correlation between SULT1A1 Arg213His Gene Polymorphisms and Uterine Leiomyomas%SULT1A1基因Arg213His 位点多态性与子宫肌瘤发生的关联性

    Institute of Scientific and Technical Information of China (English)

    周超; 林林; 张英姿; 徐天和; 张磊磊

    2011-01-01

    目的:探讨硫酸氨基转移酶(Sulfotransferase,SULT)1A1基因Arg213His位点多态性与鲁北地区汉族女性子宫肌瘤的关系.方法:以病例-对照的研究方法,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测了123例子宫肌瘤患者和123例匹配对照者的SULT1A1基因Arg213His位点的基因型,应用条件Logistic回归等方法分析基因多态性与子宫肌瘤的关系.结果:1)SULT1A1基因Arg/Arg、Arg/His、His/His 3种基因型在子宫肌瘤与对照组中的分布存在显著性差异(P=0.011);2)与Arg/Arg基因型相比,Arg/His、His/His危险度均增加,分别为2.321倍和1.985倍(P=0.003和P=0.468);3)His等位基因可显著增加患子宫肌瘤的危险性(P=0.003,OR调整=2.296,95%CI为1.325~3.978).结论:SULT1A1基因Arg213His位点基因多态性与鲁北地区汉族女性子宫肌瘤的发生有关,增加了子宫肌瘤的患病风险.%Objective: To study the correlation between polymorphisms of SULT1A1 with the risk of uterine leiomyoma interaction among Han Chinese in Northern QiLu.Methods: Arg213His genotypes of the SULT1A1 gene were detected using polymerase chain reaction-restriction fragment length polymorphism in a case-control study.A total of 123 cases of uterine leiomyomas and 123 controls were included.Multivariate logistic regression analysis was used to estimate the risk of developing uterine leiomyomas associated with environmental exposures of the SULT1A1 genotype.Results: ( 1 ) The SULT1A1 polymorphisms of the Arg/Arg, Arg/His, and His/His genotypes in the uterine leiomyoma group and the control group were significantly different ( P = 0.011 ); ( 2 ) Comparedwith that of the Arg/Arg genotype, the risk of the Arg/His was genotype and His/His was both increased, by 2.321 times and 1.985 times ( P = 0.003 and P = 0.468 ).( 3 ) The risk was significantly higher among uterine leiomyoma patients with the His allele ( OR adjusted = 2.296, 95 % CI 1.325-3.978, P = 0

  20. Investigation of Antibiotic Resistance Genes (ARGs) in Landfill%垃圾填埋场抗生素抗性基因初探

    Institute of Scientific and Technical Information of China (English)

    李蕾; 徐晶; 赵由才; 宋立岩

    2015-01-01

    Antibiotic resistant genes (ARGs), an emerging contaminant, have been detected worldwide in various environments such as sediments and river. However, little is known about ARGs distribution in landfill. In this study, we investigated five ARGs [sulfonamides resistant genes (sul and sul ), chloramphenicols resistant gene ( cat), β-lactams resistant gene ( bla-SHV), and tetracyclines resistant gene (tetW)] in refuse samples collected from jiangcungou landfill (Xi’an, China) by real-time PCR. We then correlated the ARGs and physiochemical properties of refuse to examine the link between them. Results showed that all tested ARGs have been detected in all samples, suggesting that landfill served as ARGs reservoir. The highest copies numbers of sul , sul , tetW, bla-SHV, and cat were (3. 70 ± 0. 06) × 108 copies•g - 1 (dry refuse), (9. 33 ± 0. 06) × 106 copies•g - 1 (dry refuse), (2. 27 ± 0. 08) × 105 copies•g - 1 ( dry refuse), (3. 68 ± 0. 09) × 104 copies•g - 1 ( dry refuse), and (1. 39 ± 0. 10) × 104 copies•g - 1 ( dry refuse), respectively. Further, sul , sul , and cat positively correlated to moisture and sul and cat negatively correlated to pH.%不同环境介质中抗生素抗性基因普遍存在,但是在垃圾填埋场中抗生素抗性基因尚无相关报道.本实验以西安江村沟垃圾填埋场为研究对象,采集不同方位不同深度垃圾样品,分析垃圾理化性质,用荧光定量 PCR 检测磺胺类抗生素抗性基因(sul 和sul )、抗氯霉素类抗生素抗性基因(cat)、β-内酰胺类抗生素抗性基因(bla-SHV),以及四环素类抗生素抗性基因(tetW)等5种抗生素抗性基因的含量,以相关性分析垃圾理化性质与抗性基因的关联.结果表明,5种抗生素抗性基因均存在于垃圾中,基因拷贝数(以干土计)最大值分别为:(3.70±0.06)×108 copies•g -1( sul )、(9.33±0.06)×106 copies•g -1(sul )、(2.27±0.08)×105 copies•g -1( tetW)、(3.68±0.09)×104 copies

  1. Severe respiratory phenotype caused by a de novo Arg528Gly mutation in the CACNA1S gene in a patient with hypokalemic periodic paralysis.

    Science.gov (United States)

    Kil, Tae-Hwan; Kim, June-Bum

    2010-05-01

    Hypokalemic periodic paralysis (HOKPP) is a rare disorder characterized by episodic muscle weakness with hypokalemia. Mutations in the CACNA1S gene, which encodes the alpha 1-subunit of the skeletal muscle L-type voltage-dependent calcium channel, have been reported to be mainly responsible for HOKPP. The paralytic attacks generally spare the respiratory muscles and the heart. Here, we report the case of a 16-year-old boy who presented with frequent respiratory insufficiency during the severe attacks. Mutational analysis revealed a heterozygous c.1582C>G substitution in the CACNA1S gene, leading to an Arg528Gly mutation in the protein sequence. The parents were clinically unaffected and did not show a mutation in the CACNA1S gene. A de novo Arg528Gly mutation has not previously been reported. The patient described here presents the unique clinical characteristics, including a severe respiratory phenotype and a reduced susceptibility to cold exposure. The patient did not respond to acetazolamide and showed a marked improvement of the paralytic symptoms on treatment with a combination of spironolactone, amiloride, and potassium supplements. Copyright 2009 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  2. Association of Gln27Glu and Arg16Gly polymorphisms in Beta2-adrenergic receptor gene with obesity susceptibility: a meta-analysis.

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    Hongxiu Zhang

    Full Text Available BACKGROUND: The beta2-adrenergic receptor (ADRB2 gene polymorphism has been implicated in susceptibility to obesity, but study results are still controversial. OBJECTIVE: The present meta-analysis is performed to determine whether there are any associations between the Gln27Glu (rs1042714 or the Arg16Gly (rs1042713 polymorphisms in ADRB2 and obesity susceptibility. METHODS: The PubMed (1950-2014, Embase (1974-2014, and China National Knowledge Infrastructure (CNKI, 1994-2014 databases were searched using the search terms ("Beta2-adrenergic receptor", "β2-adrenergic receptor" or "ADRB2", "polymorphism," and "obesity". Fixed- or random-effects pooled measures were determined on the bias of heterogeneity tests across studies. Publication bias was examined by Egger's test and the modified Begg's test. RESULTS: Eighteen published articles were selected for meta-analysis. Overall analyses showed that rs1042714 (Gln27Glu was associated with significantly increased obesity risk in the heterozygote model (Gln/Glu vs. Gln/Gln: OR: 1.16, 95% CI: 1.04-1.30, I2 = 49%, P = 0.009 and the dominant model (Gln/Glu + Glu/Glu vs. Gln/Gln: OR: 1.2, 95% CI: 1.00-1.44, I2 = 55%, P = 0.04, whereas no significant association was found in the other models for rs1042714. Also, no significant association was found between the rs1042713 (Arg16Gly gene polymorphism and the risk of obesity in all genetic models. In addition, neither rs1042713 (Arg16Gly nor rs1042714 (Gln27Glu showed any significant association with obesity susceptibility when the population were stratified based on gender. CONCLUSION: Our meta-analysis revealed that the rs1042714 (Gln27Glu polymorphism is associated with obesity susceptibility. However, our results do not support an association between rs1042713 (Arg16Gly polymorphisms and obesity in the populations investigated. This conclusion warrants confirmation by more case-control and cohort studies.

  3. Ophthalmic findings in a family with early-onset isolated ectopia lentis and the p.Arg62Cys mutation of the fibrillin-1 gene (FBN1).

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    Zhao, Jun-Hong; Jin, Tian-Bo; Liu, Qing-Bo; Chen, Chao; Hu, Hai-Tao

    2013-01-01

    The purpose of this paper is to describe ophthalmic findings in a family with isolated ectopia lentis (EL) caused by a specific FBN1 mutation. Detailed family histories and clinical data were recorded for six isolated EL patients of 11 family members. The ophthalmological and systematic examinations were performed on patients and unaffected members of the investigated family. The detailed ocular examinations included visual acuity, anterior chamber depth, pupil size, lens location, optometry, central corneal thickness, keratometry, slitlamp examination, fundus examination, axial length, ocular B-ultrasound, gonioscope checking, ultrasound biomicroscopy (UBM) and intraocular pressure (IOP; Goldmann applanation tonometer). Systematic examinations included the measurement of echocardiogram, height, arm span, skull, face, jaw, tooth, breast bone, spinal column, and skin. Genomic DNA was extracted using the phenol-chloroform extraction method for all subjects, and sequencing was carried out on an ABI Prism 3730 Genetic Analyzer. A heterozygous mutation, c.184C>T (p.Arg62Cys) in exon 2 of FBN1 was identified in all affected members but was not found in any unaffected member of the family. Our study presented detailed clinical manifestations, including some novel ophthalmic findings, such as pupillary abnormality, different types of glaucoma, and progressive hyperopia. Ophthalmic findings and the p.Arg62Cys mutation of FBN1 gene were reported in a family with early-onset isolated ectopia lentis.

  4. Leptin Receptor Gene Gln223Arg Polymorphism Is Not Associated with Hypertension: A Preliminary Population-Based Cross-Sectional Study

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    Geórgia das Graças Pena

    2014-01-01

    Full Text Available Hypertension is responsible for high morbidity and mortality as one of the most important cardiometabolic risk factors. The aim of the study was to investigate whether the Gln223Arg in the leptin receptor (LEPR influences the prevalence of hypertension. A cross-sectional study was carried out in individuals aged ≥ 18 years. Polymorphism identification was performed using PCR-RFLP analysis. Participants with blood pressure ≥ 140/90 mmHg or medication use were considered hypertensive. Frequencies, means, cross-tabulations, and multivariate models were produced to study differences in hypertension prevalence by genotypes. The study includes 470 participants. The frequency of GG polymorphism variant was 10.43%, 46.81% AG, and 42.77% AA. The distribution of hypertension frequency by LEPR genotypes was the following: AA 43.8%, AG 40.4%, and GG 40.8%; there were no significant differences between groups. Comparative analysis which used multivariate Poisson regression adjusted by many potential confounders (age, sex, schooling, smoking, alcohol intake, obesity, and family history of parental obesity did not modify this result. In this large sample of population-based study, the association of the LEPR Gln223Arg gene polymorphism with hypertension was not observed.

  5. The Effect of a Novel c.820C>T (Arg274Trp) Mutation in the Mitofusin 2 Gene on Fibroblast Metabolism and Clinical Manifestation in a Patient

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    Kawalec, Maria; Kabzińska, Dagmara; Kochański, Andrzej; Krzyśko, Krystiana A.; Zabłocka, Barbara

    2017-01-01

    Charcot-Marie-Tooth disease type 2A (CMT2A) is an autosomal dominant axonal peripheral neuropathy caused by mutations in the mitofusin 2 gene (MFN2). Mitofusin 2 is a GTPase protein present in the outer mitochondrial membrane and responsible for regulation of mitochondrial network architecture via the fusion of mitochondria. As that fusion process is known to be strongly dependent on the GTPase activity of mitofusin 2, it is postulated that the MFN2 mutation within the GTPase domain may lead to impaired GTPase activity, and in turn to mitochondrial dysfunction. The work described here has therefore sought to verify the effects of MFN2 mutation within its GTPase domain on mitochondrial and endoplasmic reticulum morphology, as well as the mtDNA content in a cultured primary fibroblast obtained from a CMT2A patient harboring a de novo Arg274Trp mutation. In fact, all the parameters studied were affected significantly by the presence of the mutant MFN2 protein. However, using the stable model for mitofusin 2 obtained by us, we were next able to determine that the Arg274Trp mutation does not impact directly upon GTP binding. Such results were also confirmed for GTP-hydrolysis activity of MFN2 protein in patient fibroblast. We therefore suggest that the biological malfunctions observable with the disease are not consequences of impaired GTPase activity, but rather reflect an impaired contribution of the GTPase domain to other MFN2 activities involving that region, for example protein-protein interactions. PMID:28076385

  6. Association between essential hypertension and polymorphisms of beta 1 adrenergic receptor gene G1165C (Gly389Arg) in Chinese Mongolian population

    Institute of Scientific and Technical Information of China (English)

    Rile Hu; Shigang Zhao; Guangming Niu; Chunyu Zhang; Zhiguang Wang; Mingfang Jiang

    2006-01-01

    BACKGROUND: The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population.OBJECTIVE: To analyze the association between the polymorphism of beta1 adrenergic receptor (β1-AR)gene G1165C (Arg389Gly), an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population.DESIGN: A cross-sectional study.SETTINGS: Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society.PARTICIPANTS: The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure: ① Normal blood pressure group (n=117): systolic blood pressure (SBP) < 140 mm Hg (1 mm Hg =0.133 kPa), diastolic blood pressure (DBP) < 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group (n=122): including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation.METHODS: The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Peripheral venous blood (5 mL) was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR G1165C (Gly389Arg) genotype were detected with the Sequenom system

  7. A non-synonymous coding change in the CYP19A1 gene Arg264Cys (rs700519 does not affect circulating estradiol, bone structure or fracture

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    Wang Jenny Z

    2011-12-01

    Full Text Available Abstract Background The biosynthesis of estrogens from androgens is catalyzed by aromatase P450 enzyme, coded by the CYP19A1 gene on chromosome 15q21.2. Genetic variation within the CYP19A1 gene sequence has been shown to alter the function of the enzyme. The aim of this study is to investigate whether a non-synonymous Arg264Cys (rs700519 single nucleotide polymorphism (SNP is associated with altered levels of circulating estradiol, areal bone mineral density or fracture. Methods This population- based study of 1,022 elderly Caucasian women (mean age 74.95 ± 2.60 years was genotyped for the rs700519 SNP were analyzed to detect any association with endocrine and bone phenotypes. Results The genotype frequencies were 997 wildtype (97.6%, 24 heterozygous (2.3% and 1 homozygous (0.1%. When individuals were grouped by genotype, there was no association between the polymorphism and serum estradiol (wildtype 27.5 ± 16.0; variants 31.2 ± 18.4, P = 0.27. There was also no association seen on hip bone mineral density (wildtype 0.81 ± 0.12; 0.84 ± 0.14 for variants, P = 0.48 or femoral neck bone mineral density (0.69 ± 0.10 for wildtype; 0.70 ± 0.12 for variants, P = 0.54 before or after correction of the data with age, height, weight and calcium therapy. There were also no associations with quantitative ultrasound measures of bone structure (broadband ultrasound attenuation, speed of sound and average stiffness. Conclusions In a cohort of 1,022 elderly Western Australian women, the presence of Arg264Cys (rs700519 polymorphism was not found to be associated with serum estradiol, bone structure or phenotypes.

  8. Polymorphism Trp64Arg of beta 3 adrenoreceptor gene: allelic frequencies and influence on insulin resistance in a multicenter study of Castilla-León Polimorfismo TRP64ARG del gen receptor beta 3: frecuencia alélica e influencia en la resistencia a la insulina en un estudio multicéntrico de Castilla y León

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    D. A. de Luis

    2010-04-01

    Full Text Available Background and objective: The genetic variant (Trp64Arg is a missense mutation located within the beta3 adrenoreceptor (Beta3AR. The aim of our study was to investigate the influence of Trp64Arg polymorphism in the Beta3AR gene on insulin resistance in obese patients and the allelic distribution of this polymorphismin a geographic area of Spain. Design: A population of 264 obese patients was analyzed. A bioimpedance, blood pressure, an assessment of nutritional intake, and biochemical parameters were measured. The beta 3 adrenoreceptor gene polymorphism(Trp64Arg was genotyped. Results: Two hundred and twenty six patients (77 males/149 females (85.6% had the genotype Trp64/Trp64 (wild type group with and average age of 41.12 ± 13.1 years and 38 patients (16 males/22 females Trp64/Arg64 (14.4% (mutant type group with an average age of 40.5 ± 12.7 years. High frequencies of Arg64 allele were observed in Salamanca and Valladolid. In the mutant type group, HOMA (3.75 ± 2.77 vs 5.27 ± 5.4; p Introducción y objetivos: La variante genética (Trp64Arg es una mutación localizada en el adrenoreceptor Beta 3 (Beta3AR. El objetivo de nuestro trabajo es evaluar la influencia de el polimorfismo Trp64Arg del gen de Beta3AR sobre la resistencia a la insulina en pacientes obesos, así como la distribución alélica de este polimorfismo en un área geográfica de España. Diseño: Una muestra de 264 pacientes obesos fue analizada. Se realizó una bioimpedancia, evaluación nutricional y análisis bioquímico. Se genotiparon a los pacientes en función delpolimorfismos Tr64Arg del gen adrenoreceptor-beta 3. Resultados: Un total de 227 pacientes (77 varones/149 mujeres (85,6% presentaron el genotipo Trp64/Trp64 (grupo genotipo salvaje, con una media de edad de 41,12 ± 13,1 años y un total de 38 pacientes (16 varones/22 mujeres Trp64/Arg64 (14,4% (grupo genotipo mutante con una edad media de 40,5 ± 12,7 años. Se detectó una alta frecuencia alélica (Arg64

  9. Epigenetic Perturbations by Arg882-Mutated DNMT3A Potentiate Aberrant Stem Cell Gene-Expression Program and Acute Leukemia Development.

    Science.gov (United States)

    Lu, Rui; Wang, Ping; Parton, Trevor; Zhou, Yang; Chrysovergis, Kaliopi; Rockowitz, Shira; Chen, Wei-Yi; Abdel-Wahab, Omar; Wade, Paul A; Zheng, Deyou; Wang, Gang Greg

    2016-07-11

    DNA methyltransferase 3A (DNMT3A) is frequently mutated in hematological cancers; however, the underlying oncogenic mechanism remains elusive. Here, we report that the DNMT3A mutational hotspot at Arg882 (DNMT3A(R882H)) cooperates with NRAS mutation to transform hematopoietic stem/progenitor cells and induce acute leukemia development. Mechanistically, DNMT3A(R882H) directly binds to and potentiates transactivation of stemness genes critical for leukemogenicity including Meis1, Mn1, and Hoxa gene cluster. DNMT3A(R882H) induces focal epigenetic alterations, including CpG hypomethylation and concurrent gain of active histone modifications, at cis-regulatory elements such as enhancers to facilitate gene transcription. CRISPR/Cas9-mediated ablation of a putative Meis1 enhancer carrying DNMT3A(R882H)-induced DNA hypomethylation impairs Meis1 expression. Importantly, DNMT3A(R882H)-induced gene-expression programs can be repressed through Dot1l inhibition, providing an attractive therapeutic strategy for DNMT3A-mutated leukemias.

  10. A novel BTK gene mutation, c.82delC (p.Arg28 Alafs*5), in a Korean family with X-linked agammaglobulinemia

    Science.gov (United States)

    Lee, Jeongeun; Rhee, Minhee; Min, Taek Ki; Bang, Hae In; Jang, Mi-Ae; Kang, Eun-Suk; Kim, Hee-Jin; Pyun, Bok Yang

    2016-01-01

    X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Bruton’s tyrosine kinase (BTK) gene mutations. These mutations cause defects in B-cell development, resulting in the virtual absence of these lymphocytes from the peripheral circulation. Consequently, this absence leads to a profound deficiency of lg all isotypes, and an increased susceptibility to encapsulated bacterial infections. A 15-month-old Korean boy presented with recurrent sinusitis and otitis media after 6 months of age, and had a family history of 2 maternal uncles with XLA. Laboratory tests revealed a profound deficiency of Ig isotypes, and a decreased count of CD19+ B cells in the peripheral circulation. Based on his family history and our laboratory test results, he was diagnosed with XLA. We performed BTK gene analysis of peripheral blood samples obtained from family members to confirm the diagnosis. Mutational analysis revealed a novel hemizygous frameshift mutation (c.82delC, p.Arg28Alafs*5), in the BTK gene. His mother and maternal grandmother were heterozygous carriers of this mutation and his two maternal uncles were hemizygous at the same position. After XLA diagnosis, intravenous immunoglobulin (400 mg/kg, monthly) treatment was initiated; recurrent sinusitis and otitis media were subsequently brought under control. To our knowledge, this is the first reported case of a Korean pedigree with a novel mutation in the BTK gene. PMID:28018445

  11. Sequence analysis of a 9873 bp fragment of the left arm of yeast chromosome XV that contains the ARG8 and CDC33 genes, a putative riboflavin synthase beta chain gene, and four new open reading frames.

    Science.gov (United States)

    Casas, C; Aldea, M; Casamayor, A; Lafuente, M J; Gamo, F J; Gancedo, C; Ariño, J; Herrero, E

    1995-09-15

    The DNA sequence of a 9873 bp fragment located near the left telomere of chromosome XV has been determined. Sequence analysis reveals seven open reading frames. One is the ARG8 gene coding for N-acetylornithine aminotransferase. Another corresponds to CDC33, which codes for the initiation factor 4E or cap binding protein. The open reading frame AOE169 can be considered as the putative gene for the Saccharomyces cerevisiae riboflavin synthase beta chain, since its translation product shows strong homology with four prokaryotic riboflavin synthase beta chains.

  12. A Gly15Arg mutation in the Interleukin-10 gene reduces secretion of Interleukin-10 in Crohn disease

    NARCIS (Netherlands)

    Linde, van der K.; Boor, P.P.C.; Sandkuijl, L.A.; Meijssen, M.A.C.; Savelkoul, H.F.J.; Wilson, J.H.P.; Rooij, F.W.M.

    2003-01-01

    Background: Genetic susceptibility, probably involving cytokines and their receptors, plays an important role in inflammatory bowel disease (IBD). In this study we examine the potential role of the interleukin-10 (IL-10) gene as a susceptibility gene in IBD. Methods: We studied 17 sib-pairs with

  13. A Gly15Arg mutation in the Interleukin-10 gene reduces secretion of Interleukin-10 in Crohn disease

    NARCIS (Netherlands)

    Linde, van der K.; Boor, P.P.C.; Sandkuijl, L.A.; Meijssen, M.A.C.; Savelkoul, H.F.J.; Wilson, J.H.P.; Rooij, F.W.M.

    2003-01-01

    Background: Genetic susceptibility, probably involving cytokines and their receptors, plays an important role in inflammatory bowel disease (IBD). In this study we examine the potential role of the interleukin-10 (IL-10) gene as a susceptibility gene in IBD. Methods: We studied 17 sib-pairs with eit

  14. The Trp64Arg amino acid polymorphism of the beta3-adrenergic receptor gene does not contribute to the genetic susceptibility of diabetic microvascular complications in Caucasian type 1 diabetic patients

    DEFF Research Database (Denmark)

    Tarnow, L; Urhammer, S A; Mottlau, B

    1999-01-01

    OBJECTIVE: The beta3-adrenergic receptor is involved in regulation of microvascular blood flow. A missense mutation (Trp64Arg) in the beta3-adrenergic receptor gene has been suggested as a risk factor for proliferative retinopathy in Japanese type 2 diabetic patients. The aim of the present study...

  15. Autosomal dominant rhegmatogenous retinal detachment associated with an Arg453Ter mutation in the COL2A1 gene.

    NARCIS (Netherlands)

    Go, S.L.; Maugeri, A.; Mulder, J.J.S.; Driel, M.A. van; Cremers, F.P.M.; Hoyng, C.B.

    2003-01-01

    PURPOSE: To investigate the clinical features and molecular causes of autosomal dominant rhegmatogenous retinal detachment (RRD) in two large families. METHODS: Clinical examination and linkage analysis of both families using markers flanking the COL2A1 gene associated with Stickler syndrome type 1,

  16. Research method and progress on antibiotics resistance genes(ARGs) in air%空气中抗性基因(ARGs)的研究方法及研究进展

    Institute of Scientific and Technical Information of China (English)

    贺小萌; 曹罡; 邵明非; 李继

    2014-01-01

    The long-term overuse of antibiotics lead to the emergence of antibiotic resistant bacteria and accelerate the transport and the spread of antibiotic resistance genes ( ARGs ) in different environmental matrix, which poses potential health risks to humans and animals. As a new category of environmental contaminants, ARGs have been one of the hot topics in the area of environmental research in recent years. Most research, however, focuses on AGRs in water, soil and sediment. There have been only a few studies on ARGs in air. This paper summarizes the research progress of ARGs in air and discusses the methods that can be used for collecting and detecting ARGs samples in air. The aim of this paper is to provide the scientific basis and technical strategies to support the development of studies on ARGs in air.%抗生素的长期滥用导致大量耐药菌的出现,并加剧抗生素抗性基因( ARGs)在不同环境介质中传播扩散,对人类和动物健康造成潜在威胁。作为一种新型污染物,ARGs已经成为近年来环境研究领域的热点之一。然而目前多数研究关注的是水、土壤和沉积物中的ARGs,国内外对空气中ARGs的研究相对较少且零散。本文综述了空气中ARGs的国内外研究现状,并探讨了空气中ARGs样品的采集和检测方法,旨在为空气中ARGs的研究提供科学依据和技术策略。

  17. Survival bias and drug interaction can attenuate cross-sectional case-control comparisons of genes with health outcomes. An example of the kinesin-like protein 6 (KIF6 Trp719Arg polymorphism and coronary heart disease

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    Pendyala Lakshmana

    2011-03-01

    Full Text Available Abstract Background Case-control studies typically exclude fatal endpoints from the case set, which we hypothesize will substantially underestimate risk if survival is genotype-dependent. The loss of fatal cases is particularly nontrivial for studies of coronary heart disease (CHD because of significantly reduced survival (34% one-year fatality following a coronary attack. A case in point is the KIF6 Trp719Arg polymorphism (rs20455. Whereas six prospective studies have shown that carriers of the KIF6 Trp719Arg risk allele have 20% to 50% greater CHD risk than non-carriers, several cross-sectional case-control studies failed to show that carrier status is related to CHD. Computer simulations were therefore employed to assess the impact of the loss of fatal events on gene associations in cross-sectional case-control studies, using KIF6 Trp719Arg as an example. Results Ten replicates of 1,000,000 observations each were generated reflecting Canadian demographics. Cardiovascular disease (CVD risks were assigned by the Framingham equation and events distributed among KIF6 Trp719Arg genotypes according to published prospective studies. Logistic regression analysis was used to estimate odds ratios between KIF6 genotypes. Results were examined for 33%, 41.5%, and 50% fatality rates for incident CVD. In the absence of any difference in percent fatalities between genotypes, the odds ratios (carriers vs. noncarriers were unaffected by survival bias, otherwise the odds ratios were increasingly attenuated as the disparity between fatality rates increased between genotypes. Additional simulations demonstrated that statin usage, shown in four clinical trials to substantially reduce the excess CHD risk in the KIF6 719Arg variant, should also attenuate the KIF6 719Arg odds ratio in case-control studies. Conclusions These computer simulations show that exclusions of prior CHD fatalities attenuate odds ratios of case-control studies in proportion to the difference

  18. Comparative functional characterization of novel non-syndromic GJB2 gene variant p.Gly45Arg and lethal syndromic variant p.Gly45Glu

    Science.gov (United States)

    Gordhandas, Jeenal A.; Pique, Lynn

    2016-01-01

    We characterized a novel GJB2 missense variant, c.133G>A, p.Gly45Arg, and compared it with the only other variant at the same amino acid position of the connexin 26 protein (Cx26) reported to date: c.134G>A, p.Gly45Glu. Whereas both variants are associated with hearing loss and are dominantly inherited, p.Gly45Glu has been implicated in the rare fatal keratitis-ichthyosis-deafness (KID) syndrome, which results in cutaneous infections and septicemia with premature demise in the first year of life. In contrast, p.Gly45Arg appears to be non-syndromic. Subcellular localization experiments in transiently co-transfected HeLa cells demonstrated that Cx26-WT (wild-type) and p.Gly45Arg form gap junctions, whereas Cx26-WT with p.Gly45Glu protein does not. The substitution of a nonpolar amino acid glycine in wildtype Cx26 at position 45 with a negatively charged glutamic acid (acidic) has previously been shown to interfere with Ca2+ regulation of hemichannel gating and to inhibit the formation of gap junctions, resulting in cell death. The novel variant p.Gly45Arg, however, changes this glycine to a positively charged arginine (basic), resulting in the formation of dysfunctional gap junctions that selectively affect the permeation of negatively charged inositol 1,4,5-trisphosphate (IP3) and contribute to hearing loss. Cx26 p.Gly45Arg transfected cells, unlike cells transfected with p.Gly45Glu, thrived at physiologic Ca2+ concentrations, suggesting that Ca2+ regulation of hemichannel gating is unaffected in Cx26 p.Gly45Arg transfected cells. Thus, the two oppositely charged amino acids that replace the highly conserved uncharged glycine in p.Gly45Glu and p.Gly45Arg, respectively, produce strikingly different effects on the structure and function of the Cx26 protein. PMID:27761313

  19. Studies of associations between the Arg389Gly polymorphism of the beta1-adrenergic receptor gene (ADRB1) and hypertension and obesity in 7677 Danish white subjects

    DEFF Research Database (Denmark)

    Gjesing, A P; Andersen, G; Albrechtsen, A

    2007-01-01

    Activation of the beta(1)-adrenergic receptor (ADRB1) causes increased lipolysis in adipose tissue and enhances cardiac output. Analysis of the association of the functional ADRB1 Arg389Gly variant with obesity and hypertension has given ambiguous results. To clarify the potential impact of this ......Activation of the beta(1)-adrenergic receptor (ADRB1) causes increased lipolysis in adipose tissue and enhances cardiac output. Analysis of the association of the functional ADRB1 Arg389Gly variant with obesity and hypertension has given ambiguous results. To clarify the potential impact...... of this variant on obesity and hypertension in the general population, we examined the Arg389Gly variant in a relatively large-scale population-based study....

  20. LEPR Gene Gln223Arg Polymorphism in Chinese Families with Type 2Diabetes%2型糖尿病家系患者LEPR基因Gln223Arg多态性的研究

    Institute of Scientific and Technical Information of China (English)

    孙宏; 杨泽; 苗长青; 赵晓雯; 张慧娟; 李艺萍; 梁立波; 曹佳; 王月影; 孙亮

    2011-01-01

    目的:研究黑龙江地区汉族人2型糖尿病家系的LEPR基因Gln223Arg多态性,探讨其与2型糖尿病发病的关系.方法:应用聚合酶链式反应-限制性内切酶长度多态性(PCR-RFLP)技术,对来自于黑龙江地区120个2型糖尿病家系中的210例2型糖尿病患者及319例正常对照的LEPR基因Gln223Arg (668 A→G)位点进行基因分型.结果:LEPR基因Gln223Arg三种基因型在病例组和对照组间整体分布有统计学意义(P=0.034,df=2);除AG基因型(x2=4.550,P<0.01)外,其余各基因型及等位基因在病例组和对照组间分布未见显著性差异(P>0.05).结论:LEPR基因Gln223Arg多态性与黑龙江地区汉族人2型糖尿病有关,LEPR基因可能为中国人2型糖尿病发病的相关易感基因.%Objective: To detect LEPR gene Gln223Arg polymorphism in Heilongjiang Han families with type 2 diabetes and to investigate their relationship with type 2 diabetes. Methods: PCR-RFLP method was used to test the polymorphisms of LEPR Gln223Arg (668 A-*G) in 210 individuals from 120 type 2 diabetes families and 319 normal control subjects in Heilongjiang area. Results: The overall distribution of the three genotypes of LEPR gene Gln223 Arg between cases and controls was significantly different (P=0.034, df=2). Except AG genotype (x2=.550, PO.01), the distribution of the rest of the genotypes and alleles between cases and controls had no significant difference (P>0.05). Conclusion: LEPR gene Gln223Arg polymorphism is related to type 2 diabetes in Heilongjiang Han nationality. LEPR gene may be a related gene of type 2 diabetes in Chinese.

  1. 畜禽粪便中抗生素抗性基因(ARGs)污染问题及环境调控%Pollution and Environmental Regulation of Antibiotic Resistance Genes(ARGs)in Livestock Manure

    Institute of Scientific and Technical Information of China (English)

    邹威; 罗义; 周启星

    2014-01-01

    There are increasing concerns about contamination of antibiotic resistance genes(ARGs)due to extensive uses of antibiotics in livestock and poultry breeding industries. After having induced in animal guts, antibiotic resistance bacteria are excreted via feces and then enter into soil environment through horizontal gene transfers, thus increasing the risk of ARGs propagation in soil and groundwater. It is un-known whether composting, a traditional method for utilization of animal wastes, could eliminate ARGs. This article summarized the current pollution situation of ARGs in livestock manure, and reviewed the changes of microbial community structure and their influencing factors and the dynamics of ARGs during composting. It is recommended that composting could be used as an effective way to reduce ARGs. During composting, high temperature could effectively kill antibiotic resistance bacteria and plasmids. Also chemical inhibitors such as lime nitro-gen, amine and benzopyrrole could directly diminish enteric microorganisms, thus decreasing the abundance of ARGs. It is necessary to car-ry out a comprehensive research on ARGs removal through composting to mitigate the propagation of ARGs in the environment.%抗生素在畜禽养殖业的大量使用造成抗生素抗性基因(ARGs)污染日益严重。动物体内诱导出的抗性菌株随粪便排出后,通过基因水平转移进入土壤进而污染土壤和地下水环境。堆肥作为一种将粪便资源化的优良传统方法,能否有效去除畜禽粪便中的ARGs而防止环境污染值得探讨。通过总结畜禽粪便ARGs污染现状,粪便堆肥过程中微生物群落结构变化与影响微生物变化的因素以及堆肥可能对粪便中ARGs造成的影响,提出将堆肥作为去除畜禽粪便中ARGs的一种有效手段,利用堆肥产生的高温去除抗性菌株和抗性质粒等,并且考虑加入能直接灭杀肠道微生物的化学抑制剂(如石灰氮、胺类、

  2. Review on distribution and removal of antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs)%污水处理厂抗生素抗性基因分布和去除研究进展

    Institute of Scientific and Technical Information of China (English)

    窦春玲; 郭雪萍; 尹大强

    2013-01-01

    Low concentrations of persistent antibiotics lead to increasing bacterial resistance in the environment. Antibiotic resistance genes ( ARGs) are a serious threat to ecology and human health. In wastewater treatment plants (WWTPs), ARGs from various pollutant sources, discharging into natural water and soils, are the major emission source. The purpose of this paper is to summarize the research work on distribution and removal of ARGs in the WWTPs. Several studies show that the distribution of ARGs is relevant to the ARGs species, region and the concentrations of antibiotics, and the removal efficiency is highly dependant on the treatment processes, even influenced by the process parameters. However, traditional processes are not effective. In addition, future the research on ARGs in the WWTPs is proposed.%环境中低浓度抗生素的持续存在导致细菌抗性增强,严重威胁生态与人类健康。污水处理厂接收各污染源排放的抗性基因( ARGs),并通过不同途径排放到自然水体和土壤中,是环境中主要的抗性基因排放源。本文总结了近来污水处理厂中抗性基因分布和去除研究进展。已有的研究表明,污水处理厂中抗性基因的分布与抗性基因种类、区域以及抗生素浓度有关,抗性基因的去除效果与工艺有很大关系,甚至受系统参数影响,而传统污水处理系统去除效果不佳。最后,对污水处理厂抗生素抗性基因研究进行了展望。

  3. 广西壮族人群CYP1B1基因Arg48Gly和Ala119Ser多态性研究%Study on gene polymorphisms of CYP1B1 Arg48Gly and Ala119Ser among Guangxi Zhuang Nationality population

    Institute of Scientific and Technical Information of China (English)

    李曙波; 廖长秀; 张梁; 李珊; 许小林; 罗莹

    2013-01-01

    Objective To investigate hereditary character of cytochrome P450 1B1 (CYP1B1) codon 48 and codon 119 among Guangxi Zhuang Nationality population (GZNP). Methods Gene polymorphisms of CYP1B1 in codon 48 and codon 119 were detected with polymerase chain reaction -restriction fragment length polymorphism techniques in 278 healthy GZNP. Linkage disequilibrium (LD) between the two loci was analyzed. The genotype frequencies of CYP1B1 codon 48 and codon 119 in GZNP were compared with other groups in China, other countries and regions. Results There was no difference between female and male population in allele and genotype frequencies of CYP1B1 Arg48Gly and Alall9Ser among GZNP. In the other hand, there was LD between the two loci (D' =0. 81, r2= 0.59). The frequency distribution of genotype in GZNP had no great differences with Shanghai and Sichuan, but those had significant differences with other contries such as Japan, India, Poland, and America (P <0. 01). Conclusion Gene polymorphisms of CYP1B1 in Arg48Gly and Alal 19Ser had LD, no gender difference, and were different from those in Other countries.%目的 研究CYP1 B1密码子48和119在广西壮族人群遗传特征.方法 用聚合酶链反应-限制性片断长度多态性技术对278例广西壮族正常成人进行CYP1B1 Arg48Gly和A1a119Ser基因分型,并分析两位点基因型是否存在连锁不平衡、性别差异及与国内外其他人群分布频率差异.结果 CYP1B1 Arg48 Gly和A1a119Ser基因分型无性别差异,且存在连锁不平衡(D1为0.81,r2为0.59),与国内四川和上海人群相应位点基因型分布频率无差异;但与日本、印度、波兰、美国黑人和白人等人群相应位点基因型分布频率差异有统计学意义(P<0.01).结论 广西壮族人群CYP1B1 Arg48Gly和A1a119Ser基因型分布频率无性别差异,且存在连锁不平衡,与其他部分种族存在明显差异.

  4. Estudios preliminares en la estandarización de un protocolo para la obtención de callos embriogénicos en dos clones de caucho (Hevea brasiliensis Müll. Arg.) de diferentes orígenes geográficos

    National Research Council Canada - National Science Library

    Santiago Cadavid Ruiz; César Augusto Hernández Rendóri; Rodrigo Hoyos; Marisol Medina S; Luis Fernando Restrepo

    2006-01-01

    ... (Hevea brasiliensis Müll. Arg.) sin llegar a obtenerse regeneración de plántulas. En todos los ensayos realizados en este estudio, se utilizaron dos clones de diferentes orígenes geográficos: el FX 3864 (suramericano) y el PB 254 (asiático...

  5. Assessment of the Role of MAP Kinase in Mediating Activity-Dependent Transcriptional Activation of the Immediate Early Gene "Arc/Arg3.1" in the Dentate Gyrus in Vivo

    Science.gov (United States)

    Chotiner, Jennifer K.; Nielson, Jessica; Farris, Shannon; Lewandowski, Gail; Huang, Fen; Banos, Karla; de Leon, Ray; Steward, Oswald

    2010-01-01

    Different physiological and behavioral events activate transcription of "Arc/Arg3.1" in neurons in vivo, but the signal transduction pathways that mediate induction in particular situations remain to be defined. Here, we explore the relationships between induction of "Arc/Arg3.1" transcription in dentate granule cells in vivo and activation of…

  6. Assessment of the Role of MAP Kinase in Mediating Activity-Dependent Transcriptional Activation of the Immediate Early Gene "Arc/Arg3.1" in the Dentate Gyrus in Vivo

    Science.gov (United States)

    Chotiner, Jennifer K.; Nielson, Jessica; Farris, Shannon; Lewandowski, Gail; Huang, Fen; Banos, Karla; de Leon, Ray; Steward, Oswald

    2010-01-01

    Different physiological and behavioral events activate transcription of "Arc/Arg3.1" in neurons in vivo, but the signal transduction pathways that mediate induction in particular situations remain to be defined. Here, we explore the relationships between induction of "Arc/Arg3.1" transcription in dentate granule cells in vivo and activation of…

  7. Expression and Characterization of ArgR, An Arginine Regulatory Protein in Corynebacterium crenatum

    Institute of Scientific and Technical Information of China (English)

    CHEN Xue Lan; ZHANG Bin; TANG Li; JIAO Hai Tao; XU Heng Yi; XU Feng; XU Hong; WEI Hua; XIONG Yong Hua

    2014-01-01

    Objective Corynebacterium crenatum MT, a mutant from C. crenatum AS 1.542 with a lethal argR gene, exhibits high arginine production. To confirm the effect of ArgR on arginine biosynthesis in C. crenatum, an intact argR gene from wild-type AS 1.542 was introduced into C. crenatum MT, resulting in C. crenatum MT. sp, and the changes of transcriptional levels of the arginine biosynthetic genes and arginine production were compared between the mutant strain and the recombinant strain. Methods Quantitative real-time polymerase chain reaction was employed to analyze the changes of the related genes at the transcriptional level, electrophoretic mobility shift assays were used to determine ArgR binding with the argCJBDF, argGH, and carAB promoter regions, and arginine production was determined with an automated amino acid analyzer. Results Arginine production assays showed a 69.9%reduction in arginine from 9.01±0.22 mg/mL in C. crenatum MT to 2.71±0.13 mg/mL (P Conclusion The arginine biosynthetic genes in C. crenatum are clearly controlled by the negative regulator ArgR, and intact ArgR in C. crenatum MT results in a significant descrease in arginine production.

  8. Evaluation of the frequency of polymorphisms in XRCC1 (Arg399Gln) and XPD (Lys751Gln) genes related to the genome stability maintenance in individuals of the resident population from Monte Alegre, PA/Brazil municipality; Avaliacao da frequencia de polimorfismos nos genes XRCC1 (Arg399Gln) e XPD (Lys751Gln) relacionados a manutencao da estabilidade do genoma em individuos da populacao residente no municipio de Monte Alegre, PA

    Energy Technology Data Exchange (ETDEWEB)

    Duarte, Isabelle Magliano

    2010-07-01

    The human exposure to ionizing radiation coming from natural sources is an inherent feature of human life on Earth. Ionizing radiation is a known genotoxic agent, which can affect biological molecules, causing DNA damage and genomic instability. The cellular system of DNA repair plays an important role in maintaining genomic stability by repairing DNA damage caused by genotoxic agents. However, genes related to DNA repair may have their role committed when presenting a certain polymorphism. This study intended to analyze the frequency of single nucleotide polymorphisms (SNPs) in genes of DNA repair XRCC1 (Arg39-9Gln) and XPD (Lys751Gln) in a: population of the city of Monte Alegre, that resides in an area of high exposure to natural radioactivity. Samples of saliva were collected from individuals of the population of Monte Alegre, in which 40 samples were of male and 46 female. Through the use of RFLP (length polymorphism restriction fragment) the frequency of homozygous genotypes and / or heterozygous was determined for polymorphic genes. The XRCC1 gene had 65.4% of the presence of the allele 399Gln and XPD gene had 32.9% of the 751Gln allele. These values are similar to those found in previous studies for the XPD gene, whereas XRCC1 showed a frequency much higher than described in the literature. The. influence of these polymorphisms, which are involved in DNA repair and consequent genotoxicity induced by radiation depends on dose and exposure factors such as smoking, statistically a factor in public health surveillance in the region. This study gathered information and molecular epidemiology for risk assessment of cancer in the population of Monte Alegre. (author)

  9. A nonsense mutation (Arg-196-Term) in exon 6 of the human TP53 gene identified in small cell lung carcinoma

    NARCIS (Netherlands)

    Hayes, VM; Oosthuizen, CJJ; Kotze, MJ; Marx, MP; Buys, CHCM

    1996-01-01

    In a search for mutations of the TP53 tumour suppressor gene in lung cancer samples from gold miners from the Witwatersrand, South Africa, using heteroduplex and single strand conformation polymorphism (SSCP) analysis, a nonsense mutation was found in exon 6, consisting of a C to T transition and re

  10. Regulation of Arginine Acquisition and Virulence Gene Expression in the Human Pathogen Streptococcus pneumoniae by Transcription Regulators ArgR1 and AhrC

    NARCIS (Netherlands)

    Kloosterman, Tomas G.; Kuipers, Oscar P.

    2011-01-01

    In this study, we investigated for the first time the transcriptional response of the human pathogen Streptococcus pneumoniae to fluctuating concentrations of arginine, an essential amino acid for this bacterium. By means of DNA microarray analyses, several operons and genes were found, the expressi

  11. Listeria monocytogenes 10403S Arginine Repressor ArgR Finely Tunes Arginine Metabolism Regulation under Acidic Conditions

    Science.gov (United States)

    Cheng, Changyong; Dong, Zhimei; Han, Xiao; Sun, Jing; Wang, Hang; Jiang, Li; Yang, Yongchun; Ma, Tiantian; Chen, Zhongwei; Yu, Jing; Fang, Weihuan; Song, Houhui

    2017-01-01

    Listeria monocytogenes is able to colonize human and animal intestinal tracts and to subsequently cross the intestinal barrier, causing systemic infection. For successful establishment of infection, L. monocytogenes must survive the low pH environment of the stomach. L. monocytogenes encodes a functional ArgR, a transcriptional regulator belonging to the ArgR/AhrC arginine repressor family. We aimed at clarifying the specific functions of ArgR in arginine metabolism regulation, and more importantly, in acid tolerance of L. monocytogenes. We showed that ArgR in the presence of 10 mM arginine represses transcription and expression of the argGH and argCJBDF operons, indicating that L. monocytogenes ArgR plays the classical role of ArgR/AhrC family proteins in feedback inhibition of the arginine biosynthetic pathway. Notably, transcription and expression of arcA (encoding arginine deiminase) and sigB (encoding an alternative sigma factor B) were also markedly repressed by ArgR when bacteria were exposed to pH 5.5 in the absence of arginine. However, addition of arginine enabled ArgR to derepress the transcription and expression of these two genes. Electrophoretic mobility shift assays showed that ArgR binds to the putative ARG boxes in the promoter regions of argC, argG, arcA, and sigB. Reporter gene analysis with gfp under control of the argG promoter demonstrated that ArgR was able to activate the argG promoter. Unexpectedly, deletion of argR significantly increased bacterial survival in BHI medium adjusted to pH 3.5 with lactic acid. We conclude that this phenomenon is due to activation of arcA and sigB. Collectively, our results show that L. monocytogenes ArgR finely tunes arginine metabolism through negative transcriptional regulation of the arginine biosynthetic operons and of the catabolic arcA gene in an arginine-independent manner during lactic acid-induced acid stress. ArgR also appears to activate catabolism as well as sigB transcription by anti

  12. XRCC1 Arg194Trp and Arg399Gln polymorphisms and arsenic methylation capacity are associated with urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Chien-I [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Huang, Ya-Li [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Chen, Wei-Jen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Lin, Ying-Chin [Department of Family Medicine, Shung Ho Hospital, Taipei Medical University, New Taipei, Taiwan (China); Department of Health Examination, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan (China); Division of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2014-09-15

    The association between DNA repair gene polymorphisms and bladder cancer has been widely studied. However, few studies have examined the correlation between urothelial carcinoma (UC) and arsenic or its metabolites. The aim of this study was to examine the association between polymorphisms of the DNA repair genes, XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln, with urinary arsenic profiles and UC. To this end, we conducted a hospital-based case–control study with 324 UC patients and 647 age- and gender-matched non-cancer controls. Genomic DNA was used to examine the genotype of XRCC1 Arg194Trp, XRCC1 Arg399Gln, XRCC3 Thr241Met, and XPD Lys751Gln by PCR-restriction fragment length polymorphism analysis (PCR-RFLP). Urinary arsenic profiles were measured by high performance liquid chromatography (HPLC) linked with hydride generator and atomic absorption spectrometry. The XRCC1 399 Gln/Gln and 194 Arg/Trp and Trp/Trp genotypes were significantly related to UC, and the odds ratio (OR) and 95% confidence interval (95%CI) were 1.68 (1.03–2.75) and 0.66 (0.48–0.90), respectively. Participants with higher total urinary arsenic levels, a higher percentage of inorganic arsenic (InAs%) and a lower percentage of dimethylarsinic acid (DMA%) had a higher OR of UC. Participants carrying XRCC1 risk diplotypes G-C/G-C, A-C/A-C, and A-T/G-T, and who had higher total arsenic levels, higher InAs%, or lower DMA% compared to those with other XRCC1 diplotypes had a higher OR of UC. Our results suggest that the XRCC1 399 Gln/Gln and 194 Arg/Arg DNA repair genes play an important role in poor arsenic methylation capacity, thereby increasing the risk of UC in non-obvious arsenic exposure areas. - Highlights: • The XRCC1 399Gln/Gln genotype was significantly associated with increased OR of UC. • The XRCC1 194 Arg/Trp and Trp/Trp genotype had a significantly decreased OR of UC. • Combined effect of the XRCC1 genotypes and poor arsenic methylation capacity on

  13. A relevance study on uterine leiomyoma and gene polymorphisms of CYP1A1 MspⅠand SULT1A1 Arg213His%CYP1A1基因MspⅠ位点和SULT1A1基因Arg213His位点多态性与子宫肌瘤的关联性研究

    Institute of Scientific and Technical Information of China (English)

    周超; 林林; 张英姿; 徐天和; 张磊磊

    2011-01-01

    目的 探讨细胞色素P450(cytochrome P450,CYP)1A1基因MspⅠ位点和硫酸氨基转移酶(sulfotransferase,SULT)1A1基因Arg213His位点多态性与鲁北地区汉族女性子宫肌瘤的关系.方法 采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)方法检测123例子宫肌瘤患者和123例健康对照组的CYP1A1基因MspⅠ位点的基因型和SULT1A1基因Arg213His位点的基因型,分析基因多态性与子宫肌瘤的关系.结果 子宫肌瘤组CYP1A1基因MspⅠ位点的基因型与对照组中的分布比较,差异无统计学意义(P=0.927);而子宫肌瘤组SULT1A1基因Arg213His位点的基因型与对照组中的分布比较,差异有统计学意义(P=0.011).CYP1A1基因MspⅠ位点和SULT1A1基因Arg213His位点多态性在子宫肌瘤的发生过程中的交互作用比较,差异有统计学意义(P=0.024).结论 CYP1A1基因MspⅠ位点多态性与鲁北地区汉族女性子宫肌瘤的易感性无显著相关;SULT1A1基因Arg213His位点多态性与鲁北地区汉族女性子宫肌瘤的发生有关,并增加了子宫肌瘤的患病风险;CYP1A1基因MspⅠ位点和SULT1A1基因Arg213His位点多态性在子宫肌瘤的发生过程中具有交互作用.

  14. Cloning and characterization of HbMT2a, a metallothionein gene from Hevea brasiliensis Muell. Arg differently responds to abiotic stress and heavy metals

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yan; Chen, Yue Yi; Yang, Shu Guang; Tian, Wei Min, E-mail: wmtian9110@126.com

    2015-05-22

    Metallothioneins (MTs) are of low molecular mass, cysteine-rich proteins. They play an important role in the detoxification of heavy metals and homeostasis of intracellular metal ions, and protecting against intracellular oxidative damages. In this study a full-length cDNA of type 2 plant metallothioneins, HbMT2a, was isolated from 25 mM Polyethyleneglycol (PEG) stressed leaves of Hevea brasiliensis by RACE. The HbMT2a was 372 bp in length and had a 237 bp open reading frame (ORF) encoding for a protein of 78 amino acid residues with molecular mass of 7.772 kDa. The expression of HbMT2a in the detached leaves of rubber tree clone RY7-33-97 was up-regulated by Me-JA, ABA, PEG, H{sub 2}O{sub 2}, Cu{sup 2+} and Zn{sup 2+}, but down-regulated by water. The role of HbMT2a protein in protecting against metal toxicity was demonstrated in vitro. PET-28a-HbMT2-beared Escherichia coli. Differential expression of HbMT2a upon treatment with 10 °C was observed in the detached leaves of rubber tree clone 93-114 which is cold-resistant and Reken501 which is cold-sensitive. The expression patterns of HbMT2a in the two rubber tree clones may be ascribed to a change in the level of endogenous H{sub 2}O{sub 2}. - Highlights: • Cloning an HbMT2a gene from rubber tree. • Analyzing expression patterns of HbMT2a upon abiotic stress and heavy metal stress. • Finding different expression patterns of HbMT2a among two Hevea germplasm. • The expressed protein of HbMT2a enhances copper and zinc tolerance in Escherichia coli.

  15. Arc/Arg3.1 Mediates Homeostatic Synaptic Scaling of AMPA Receptors

    National Research Council Canada - National Science Library

    Shepherd, Jason D; Rumbaugh, Gavin; Wu, Jing; Chowdhury, Shoaib; Plath, Niels; Kuhl, Dietmar; Huganir, Richard L; Worley, Paul F

    2006-01-01

    .... Here, we demonstrate that Arc/Arg3.1, an immediate-early gene (IEG) that is rapidly induced by neuronal activity associated with information encoding in the brain, mediates homeostatic synaptic scaling of AMPA type glutamate receptors (AMPARs...

  16. Developmental effect of the XmnI site on Ggamma-globin gene expression among newborn Hb F-Malta-I [Ggamma117(G19)His-->Arg, CAT-->CGT] heterozygotes and adult beta+ -Thalassemia homozygotes.

    Science.gov (United States)

    Pulis, Svetlana; Scerri, Christian A; Wismayer, Pierre Schembri; Galdies, Ruth; Wettinger, Stephanie Bezzina; Felice, Alex E

    2007-01-01

    Hb F-Malta-I [Ggamma117(19)His-->Arg, CAT-->CGT] is a stable and benign variant of Hb F found in 1.8% of Maltese newborn. We studied 120 Hb F-Malta-I heterozygotes and four Hb F-Malta-I homozygotes. The mean proportion of Ggamma-F-Malta-I in Hb F was 0.26 +/- 0.03 for the Hb F-Malta-I heterozygotes and 0.58 +/- 0.06 for the Hb F-Malta-I homozygotes. The Hb F-Malta-I allele was shown to occur on a background of the common Mediterranean haplotype Va [+ + - - - - - + + -]. Furthermore, the common Mediterranean haplotypes Va, IIIb [- + + + - + + + + -], I [+ + - - - - - + + +] and II [- + - + + - + + + +] accounted for most (66.2%) of the wild-type alleles among the tested Hb F-Malta-I heterozygotes. Different genotypes at the 5' epsilon HincII, Ggamma and Agamma HindIII, and 3'psibeta HincII sites (but not at the 5' Ggamma XmnI site) were found to be linked to significant variations in the proportion of Ggamma-F-Malta-I and Ggamma-globins in the Hb F of newborn Hb F-Malta-I heterozygotes. Moreover, the 5' Ggamma XmnI site was found to be associated with variations in Hb F and Ggamma-globin levels in a population of adult Maltese beta-thalassemia (thal) homozygotes. This implies that a determinant linked to the XmnI site which effects Ggamma-globin gene expression is active in anemic adults but not in normal infants.

  17. Novel homozygous mutation, c.400C>T (p.Arg134*), in the PVRL1 gene underlies cleft lip/palate-ectodermal dysplasia syndrome in an Asian patient.

    Science.gov (United States)

    Yoshida, Kazue; Hayashi, Ryota; Fujita, Hideki; Kubota, Masaya; Kondo, Mai; Shimomura, Yutaka; Niizeki, Hironori

    2015-07-01

    Cleft lip/palate-ectodermal dysplasia syndrome is a rare, autosomal recessive disorder caused by homozygous loss-of-function mutations of the poliovirus receptor-like 1 (PVRL1) gene encoding nectin-1. Nectin-1 is a cell-cell adhesion molecule that is important for the initial step in the formation of adherens junctions and tight junctions; it is expressed in keratinocytes, neurons, and the developing face and palate. Clinical manifestations comprise a unique facial appearance with cleft lip/palate, ectodermal dysplasia, cutaneous syndactyly of the fingers and/or toes, and in some cases, mental retardation. We present the first report, to our knowledge, of an Asian individual with cleft lip/palate-ectodermal dysplasia syndrome with a novel PVRL1 mutation. A 7-year-old Japanese boy, the first child of a consanguineous marriage, showed hypohidrotic ectodermal dysplasia with sparse, brittle, fine, dry hair and hypodontia, the unique facial appearance with cleft lip/palate, cutaneous syndactyly of the fingers and mild mental retardation. Scanning electron microscopic examination of the hair demonstrated pili torti and pili trianguli et canaliculi. Mutation analysis of exon 2 of PVRL1 revealed a novel homozygous nonsense mutation, c.400C>T (p.Arg134*). His parents were heterozygous for the mutant alleles. All four PVRL1 mutations identified in cleft lip/palate-ectodermal dysplasia syndrome to date, including this study, resulted in truncated proteins that lack the transmembrane domain and intracellular domain of nectin-1, which is necessary to initiate the cell-cell adhesion process.

  18. The Gly16 Allele of the Gly16Arg Single-Nucleotide Polymorphism in the β2-Adrenergic Receptor Gene Augments Perioperative Use of Vasopressors

    DEFF Research Database (Denmark)

    Nielsen, Morten; Staalsø, Jonatan Myrup; Ullum, Henrik

    2016-01-01

    receptor (ADRB2) influences perioperative arterial blood pressure and consequently the use of vasopressors. METHODS: Five hundred seventy-one Danish Caucasians undergoing neurosurgery were genotyped for 5 marker single-nucleotide polymorphisms (SNPs) within ADRB2 (Gly16Arg, Gln27Glu, Thr164Ile, Arg175Arg......, and Gly351Gly). A pairwise tagging principle was used to identify ADRB2 haplotypes. Mean arterial blood pressure (MAP) was recorded in the supine awake state and, together with administration of vasopressors (ephedrine and/or phenylephrine), for 30 minutes after induction of general anesthesia...... (sevoflurane/remifentanil or propofol/remifentanil). RESULTS: Four hundred thirteen (72%) patients received ephedrine and/or phenylephrine. Only baseline MAP (P

  19. Polymorphism of FGFR4 Gly388Arg does not confer an increased risk to breast cancer development.

    Science.gov (United States)

    Naidu, R; Har, Y C; Taib, N A

    2009-01-01

    The genotype analysis of the Gly and Arg allele at codon 388 of fibroblast growth factor receptor-4 (FGFR4) gene was evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy. The aim of the present study was to evaluate the association between the FGFR4 Gly388Arg polymorphism and breast cancer risk as well as clinicopathological parameters of the patients. The Gly/Gly, Gly/Arg, Arg/Arg, and Arg allele genotypes were detected in 46.3%, 44.4%, 9.3%, and 53.7% of breast cancer cases, respectively. The distribution of genotype (p = 0.204) and allele (p = 0.086) frequencies of FGFR4 polymorphism were not significantly different between the breast cancer cases and normal individuals. Women who were Arg/ Arg homozygotes (OR = 1.714, 95% CI 0.896-3.278), Gly/Arg heterozygotes (OR = 1.205, 95% CI 0.863-1.683), carriers of Arg allele genotype (OR = 1.269, 95% CI 0.921-1.750), or Arg allele (OR = 1.246, 95% CI 0.970-1.602) were not associated with breast cancer risk. The Arg allele genotype was significantly associated with lymph node metastases (p = 0.001) but not with other clinicopathological parameters. Our findings suggest that the polymorphic variant at codon 388 of FGFR4 gene does not confer increased risk to breast cancer development but it may be a potential genetic marker for tumor prognosis.

  20. Rubber Tree (Hevea brasiliensis Muell. Arg).

    Science.gov (United States)

    Venkatachalam, Perumal; Jayashree, Radha; Rekha, Karumamkandathil; Sushmakumari, Sreedharannair; Sobha, Sankaren; Kumari Jayasree, Parukkuttyamma; Kala, Radha Gopikkuttanunithan; Thulaseedharan, Arjunan

    2006-01-01

    Rubber tree (Hevea brasiliensis Muell. Arg.) is an important industrial crop for natural rubber production. At present, more than 9.5 million hectares in about 40 countries are devoted to rubber tree cultivation with a production about 6.5 million tons of dry rubber each year. The world supply of natural rubber is barely keeping up with a global demand for 12 million tons of natural rubber in 2020. Tapping panel dryness (TPD) is a complex physiological syndrome widely found in rubber tree plantations, which causes severe yield and crop losses in natural rubber producing countries. Currently, there is no effective prevention or treatment for this serious malady. As it is a perennial tree crop, the integration of specific desired traits through conventional breeding is both time-consuming and labour-intensive. Genetic transformation with conventional breeding is certainly a more promising tool for incorporation of agronomically important genes that could improve existing Hevea genotype. This chapter provides an Agrobacterium-mediated transformation protocol for rubber tree using immature anther-derived calli as initial explants. We have applied this protocol to generate genetically engineered plants from a high yielding Indian clone RRII 105 of Hevea brasiliensis (Hb). Calli were co-cultured with Agrobacterium tumefaciens harboring a plasmid vector containing the Hb superoxide dismutase (SOD) gene and the reporter gene used was beta-glucuronidase (GUS) gene (uidA). The selectable marker gene used was neomycin phosphotransferase (nptII) and kanamycin was used as selection agent. We found that a suitable transformation protocol for Hevea consists of a 3-d co-cultivation with Agrobacterium in the presence of 20 mM acetosyringone, 15 mM betaine HCl, and 11.55 mM proline followed by selection on medium containing 300 mg/L kanamycin. Transformed calli surviving on medium containing 300 mg/L kanamycin showed a strong GUS-positive reaction. Upon subsequent subculture into

  1. Molecular cloning and characterization of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 (hmgr1) gene from rubber tree (Hevea brasiliensis Muell. Arg.): A key gene involved in isoprenoid biosynthesis.

    Science.gov (United States)

    Venkatachalam, P; Priya, P; Jayashree, R; Rekha, K; Thulaseedharan, A

    2009-04-01

    Natural rubber (cis-1,4-polyisoprene) is a secondary metabolite produced in the laticiferous tissue of Hevea tree. Mevalonate synthesis, which is the first step in isoprenoid biosynthesis, is catalyzed by the enzyme 3-hydroxy-3-methylglutarylcoenzyme A reductase 1 (hmgr1). We have cloned and characterized a full-length cDNA as well as genomic DNA for hmgr1 gene from an elite Indian rubber clone (RRII 105). The nucleotide sequence of the genomic clone comprises 4 exons and 3 introns, giving a total length of 2440 bp. The sequences of 42 bp 5' UTR and 69 bp of the 3' UTR were also determined. The hmgr1 cDNA contained an open reading frame of 1838 bp coding for 575 amino acid protein with a theoretical pI value of 6.6 and the calculated protein M W was 61.6 kDa. The deduced amino acid sequence showed high identity with other plant hmgr1 sequences. The amino acid sequence of the Hevea hmgr1 revealed several motifs which are highly conserved and common to the other plant species. These sequence conservations suggest a strong evolutionary pressure to maintain amino acid residues at specific positions, indicating that the conserved motifs might play important roles in the structural and/or catalytic properties of the enzyme. Southern blot analysis of genomic DNA from Hevea probed with a genomic fragment indicated that there were at least three isoforms of hmgr in Hevea. This result reveals that hmgr1 is one of the members of a small gene family. (Northern blot analysis showed that hmgr1 mRNA transcripts were noticed in all tissues - latex, leaf, immature leaf, and seedlings), however, the abundance of transcript level was higher in latex cells. As one step towards a better understanding of the role that this enzyme plays in coordinating isoprenoid biosynthesis in plants, hmgr1 cDNA was over expressed in transgenic Arabidopsis plants. Transgenic plants were morphologically distinguishable from control wild-type plants and an increased expression level of hmgr1 mRNA was

  2. A novel distinctive cerebrovascular phenotype is associated with heterozygous Arg179 ACTA2 mutations

    NARCIS (Netherlands)

    Munot, Pinki; Saunders, Dawn E.; Milewicz, Dianna M.; Regalado, Ellen S.; Ostergaard, John R.; Braun, Kees P.; Kerr, Timothy; Lichtenbelt, Klaske D.; Philip, Sunny; Rittey, Christopher; Jacques, Thomas S.; Cox, Timothy C.; Ganesan, Vijeya

    2012-01-01

    Mutations in the ACTA2 gene lead to diffuse and diverse vascular diseases; the Arg179His mutation is associated with an early onset severe phenotype due to global smooth muscle dysfunction. Cerebrovascular disease associated with ACTA2 mutations has been likened to moyamoya disease, but appears to h

  3. Meta-analysis of the association between Trp64Arg polymorphism in β3-adrenergic receptor gene and overweight/obesity in children%儿童超重/肥胖与β3肾上腺素受体基因Trp64 Arg多态性的关联meta分析

    Institute of Scientific and Technical Information of China (English)

    吴静; 焦周阳; 张静; 罗强; 刘玉峰; 安金斗; 田培超; 张好好

    2016-01-01

    [Summary] In this study, PubMed, Embase, China National Knowledge Infrastructure, databases VIP Chinese Periodical Database, and Wanfang Chinese Periodical Database were systematically searched for the case-control study related β3-adrenergic receptor ( ADRB3 ) Trp64Arg gene polymorphism to overweight/obesity among children from 1962 to 2014.Twelve eligible studies with 2 222 overweight/obese children and 1 955 normal children were included according the uniform inclusion and exclusion criteria.Meta-analyses showed that Trp64Arg polymorphism was associated with significantly increased overweight/obesity risk in Arg carriers among children( OR=1.34,95%CI1.17-1.53).Afterstratificationforethnicity,highlysignificantcoorelationofTrp64Argpolymorphism to overweight/obesity in Asian children(OR=1.44, 95%CI 1.23-1.68) but not significant in Europe(OR=1.05, 95%CI 0.79-1.40).It suggested that Trp64Arg polymorphism is associated with overweight/obesity susceptibility in children.Our results support an strong association between Trp64Arg polymorphism and overweight/obesity among the Asian children investigated.%本研究通过计算机检索Pubmed、Embae、中国全文期刊数据库(包含博硕士论文数据库)、万方和维普中文科技期刊数据库,收集1962年至2014年β3肾上腺素受体(β3-adrenergic receptor, ADRB3)基因Trp64Arg多态性与儿童超重/肥胖的病例对照研究文献,共纳入12篇文献,其中儿童超重/肥胖者2222例,对照组1955人。 Meta分析结果显示,ADRΒ3基因Trp64Arg突变能够增加儿童超重/肥胖的发病风险(OR=1.34,95%CI 1.17~1.53),亚洲儿童中该基因突变型携带者超重/肥胖风险升高明显(OR=1.44,95%CI 1.23~1.68),欧洲儿童Arg携带者罹患超重/肥胖风险升高不明显(OR=1.05,95%CI 0.79~1.40)。提示β3肾上腺素受体基因Trp64Arg多态性与儿童超重/肥胖发病具有一定相关性

  4. Premilinary studies for optimiziing a protocol for obtaining embryogenic calluses in two rubber (Hevea brasiliensis Mull. Arg clones from different geographical origins Estudios preliminares en la estandarización de un protocolo para la obtención de callos embriogénicos en dos clones de caucho (Hevea brasiliensis Müll. Arg. de diferentes orígenes geográficos

    Directory of Open Access Journals (Sweden)

    Medina S. Marisol

    2006-07-01

    Full Text Available The influence of growth regulators on obtaining friable rubber (Hevea brasiliensis Müll. Arg. calluses with no plant regeneration as investigated. Two clones having different geographical origin were used in all trails carried out in this study: FX 3864 (South-American and PB 254 (Asian. Young leaves and eight- to ten-week-old seed integument from both clones were used as explants in several experiments; they were initially cultured in MH medium (Carron, et ál., 1989, modified MH medium (Montoro, et ál., 1993, 2000 and modified MS medium (Carron, et at,. 1992, no positive response being obtained by days 25 or 50. However, other trials were carried out with the integument in modified MS medium (1962, 0.67 mg/L BAP and 0.66 mg/L 2-4 D being added as medium for initiating embryogenesis, the formation of white, friable calluses being observed by day 25 in the two selected clones. These calluses were sub-cultured in MS supplemented with 0.35 mg/L BAP and 0.2 mg/L 2-4 D as callogenesis expression medium, embryogenic expression being observed in both clones by day 50. Equally friable white calluses were obtained from young leaves in the two clones in MS medium supplemented with 1.0 mg/L BAP, 1.0 mg/L ANA but without IBA and kinetin by day 25. Calluses sub-cultured in the same medium supplemented with 0.5 mg/L BAP and 0.5 mg/L ANA began to show increased friability after 50 days. culture. This work is a partial report of a macro-project for optimising a protocol for rubber (Hevea brasiliensis  multiplication by somatic embryogenesis.Se investigó la influencia de los reguladores de crecimiento para la obtención de callos friables en caucho (Hevea brasiliensis Müll. Arg. sin llegar a obtenerse regeneración de plántulas. En todos los ensayos realizados en este estudio, se utilizaron dos clones de diferentes orígenes geográficos: el FX 3864 (suramericano y el PB 254 (asiático. Para los diferentes tratamientos se utilizaron como explantes hojas j

  5. ASSOCIATION BETWEEN GLN223ARG POLYMORPHISM IN LEPTIN RECEPTOR GENE AND OVERWEIGHT-OBESITY IN A CERTAIN DISTRICT IN SHANGHAI HAN NATIONALITY%LEPR基因GIn223Arg多态性与上海某区汉族儿童的相关性研究

    Institute of Scientific and Technical Information of China (English)

    江山曦; 郭红卫; 薛琨; 朱美英; 朱俭; 罗飞宏

    2012-01-01

    目的 探究瘦素受体基因Gln223Arg多态性与上海某区儿童超重肥胖的关系及相关生化指标的相关性.方法 采用PCR-RFLP对上海松江区六所小学7-11岁超重肥胖与正常体重儿童(各262名)的血样进行LEPR基因Gln223Arg多态性检测,logistic回归分析其与儿童超重肥胖的相关性,并分析了生化指标在超重肥胖组与正常组儿童以及不同基因型间的差异. 结果 超重肥胖组与对照组之间LEPR基因Gln223Arg从频率与A等位基因频率均无统计学差异(P>0.05).对其收缩压(SBP),舒张压(DBP),胆固醇(TC),甘油三酯(TG),血糖(GLU),高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C)进行t检验,得出SBP,DBP,TG,HDL-C和LDL-C在超重肥胖组与对照组中差异显著.在控制了混杂因素BMI等后,LEPR基因Gln223Arg各基因型组的生化指标差异分析表明基因型可能与LDL-C相关(P<0.05).进一步两两比较结果表明LDL-C水平在基因型AA组比AG(P=0.019)与GG组(P=0.017)低,而AG与GG组之间的差异无统计学意义(P=0.517). 结论 LEPR基因Gln223Arg多态性可能与儿童超重肥胖的发生无关,而LDL-C(P<0.05)可能与LEPR基因Gln223Arg基因型有相关性.%Objective To evaluate the association between leptin receptor (LEPR) Gln223Arg polymorphism and overweight-obesity in children, as well as related biochemical indices. Method The subjects were from six primary schools with the age from seven to eleven, in Songjiang District, Shanghai, China. LEPR Gln223Arg polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 262 normal weight subjects and 262 overweight-obese subjects. And logistic regression was used for analysis of the LEPR Gln223Arg polymorphism with obesity. Difference of biochemical indices was analyzed between the two groups, as well as between different genotypes. Results There was no significant difference of AA genotype and A allele of LEPR gene between

  6. 污水处理厂削减耐药菌与抗性基因的研究进展%State-of-the-art removal of antibiotic resistance bacteria (ARB) and antibiotic resistance gene (ARG) in wastewater treatment plants (WWTPs)

    Institute of Scientific and Technical Information of China (English)

    佟娟; 魏源送

    2012-01-01

    长期滥用抗生素导致细菌耐药性增强,并使抗性广泛传播.污水处理厂既是耐药菌(antibiotic resistance bacteria,ARB)与抗性基因(antibiotic resistance gene,ARG)的储存库,排放的污水与污泥是向自然环境中传播抗性的重要污染源,也是削减ARB和ARG及控制抗性传播的重要环节.本文总结了天然水体中的耐药菌和抗性基因污染现状,分析了近年来耐药菌与抗性基因在污水/污泥处理过程中的转归与去除方面的研究进展,同时对将来的重点研究方向提出展望,以期为今后耐药菌和抗性基因的污染控制提供参考.%The abuse and overuse of antibiotics lead to increasing bacterial resistance to actibiotics and extensive dissemination of resistance. As a reservoir for antibiotic resistance bacteria (ARB) and antibiotic resistance gene (ARG) , the effluent and biosolids of wastewater treatment plants (WWTPs) are the important contamination sources for the antibiotic resistance dissemination. Meanwhile, WWTPs play an important role in controlling of resistance dissemination. The purpose of this paper is to summarize pollution status of antibiotic resistance in the aquatic environment, to thoroughly review the advances of removing ARB and ARG during WWTP treating processes, and to propose the future research direction.

  7. GENETIC VARIATION IN THE BETA-3-ADRENORECEPTOR GENE (TRP64ARG POLYMORPHISM) AND THEIR INFLUENCE ON ANTHROPOMETRIC PARAMETERS AND INSULIN RESISTANCE AFTER A HIGH PROTEIN/LOW CARBOHYDRATE VERSUS A STANDARD HYPOCALORIC DIET.

    Science.gov (United States)

    de Luis, Daniel Antonio; Aller, Rocío; Izaola, Olatz; de la Fuente, Beatriz; Romero, Enrique

    2015-08-01

    Introducción: la variante Trp64Arg del receptor Beta ha sido relacionada con un aumento del peso corporal y resistencia a la insulina. Objetivo: el objetivo de nuestro estudio fue investigar la influencia del polimorfismo (rs 4994) del gen del receptor adrenérgico-Beta-3 en la respuesta metabólica y la pérdida de peso en un estudio de intervención a medio plazo con una dieta con alto contenido en proteínas/baja en carbohidratos vs una dieta hipocalórica estándar (1.000 kcal / día). Material y métodos: se evaluó una muestra de 284 sujetos obesos con un diseño de ensayo aleatorio. Se realizó una evaluación nutricional al inicio y al final de un período de 9 meses en el que los sujetos recibieron una de las dos dietas (dieta HP: alta en proteínas/baja en carbohidratos vs dieta S: dieta estándar). Resultados: no hubo diferencias significativas entre los efectos positivos (sobre el peso, el índice de masa corporal, la circunferencia de la cintura, la masa grasa, la presión arterial sistólica y los niveles de leptina) en los dos genotipos con ambas dietas. Con ambas dietas y solo en el genotipo salvaje (dieta HP vs dieta S), colesterol total (-10,1 ± 3,9 mg / dl vs -10,1 ± 2,2 mg / dl; p> 0,05), colesterol LDL (-9,5 ± 2,1 mg / dl vs -8,5 ± 2,3 mg / dl; p> 0,05) y los triglicéridos (-19,1 ± 2,1 mg / dl vs -14,3 ± 2,1 mg / dl; p> 0,05) disminuyeron. La mejoría de estos parámetros fue similar en sujetos con dieta HP vs dieta HS. Con la dieta HP y solo en el genotipo salvaje, los niveles de insulina (-3,7 ± 1,9 UI / L; p.

  8. The control in cis of the position and the amount of the ARG4 meiotic double-strand break of Saccharomyces cerevisiae.

    OpenAIRE

    de Massy, B.; Nicolas, A.

    1993-01-01

    During meiosis, a transient DNA double-strand break (DSB) occurs in the promoter region (positions -200/-185) of the Saccharomyces cerevisiae ARG4 gene and is a likely intermediate in the initiation of meiotic gene conversion events in this region. We report here a functional analysis of the ARG4 DSB based on the study of various deletions in this chromosomal region. We have identified several cis-acting elements located within the -465/+3 region of the ARG4 promoter that control the formatio...

  9. Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

    DEFF Research Database (Denmark)

    Philips, Mari-Anne; Kingo, Külli; Karelson, Maire;

    2010-01-01

    MYG1 (Melanocyte proliferating gene 1, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that MYG1 mRNA expression is elevated in the skin of vitiligo patients. Our aim was to ...

  10. Promoter polymorphism -119C/G in MYG1 (C12orf10) gene is related to vitiligo susceptibility and Arg4Gln affects mitochondrial entrance of Myg1

    DEFF Research Database (Denmark)

    Philips, Mari-Anne; Kingo, Külli; Karelson, Maire

    2010-01-01

    MYG1 (Melanocyte proliferating gene 1, also C12orf10 in human) is a ubiquitous nucleo-mitochondrial protein, involved in early developmental processes and in adult stress/illness conditions. We recently showed that MYG1 mRNA expression is elevated in the skin of vitiligo patients. Our aim...

  11. Fmoc-Arg(Pbf)-OH的合成%The synthesis of Fmoc-Arg(Pbf)-OH

    Institute of Scientific and Technical Information of China (English)

    洪镛裕; 刘超程; 赵宏伟

    2006-01-01

    研究了精氨酸用9-芴甲氧羰基(Fmoc)和2,2,4,6,7-五甲基苯并呋喃-5-磺酰基(Pbf)双保护的Fmoc-Arg(Pbf)-OH的制备过程.在引入Pbf时,加入了相转移催化剂四乙基溴化铵(TEBA),提高了反应效率,减少了Pbf-Cl的水解;成盐时改为将Cbz-Arg(Pbf)-OH溶液加入到环己胺溶液中,使成盐质量有所提高,将该步收率由文献的59%提高到72%.

  12. ArgR is an essential local transcriptional regulator of the arcABC operon in Streptococcus suis and is crucial for biological fitness in an acidic environment.

    Science.gov (United States)

    Fulde, Marcus; Willenborg, Joerg; de Greeff, Astrid; Benga, Laurentiu; Smith, Hilde E; Valentin-Weigand, Peter; Goethe, Ralph

    2011-02-01

    Streptococcus suis is one of the most important pathogens in pigs and can also cause severe infections in humans. Despite its clinical relevance, very little is known about the factors that contribute to its virulence. Recently, we identified a new putative virulence factor in S. suis, the arginine deiminase system (ADS), an arginine catabolic enzyme system encoded by the arcABC operon, which enables S. suis to survive in an acidic environment. In this study, we focused on ArgR, an ADS-associated regulator belonging to the ArgR/AhrC arginine repressor family. Using an argR knockout strain we were able to show that ArgR is essential for arcABC operon expression and necessary for the biological fitness of S. suis. By cDNA expression microarray analyses and quantitative real-time RT-PCR we found that the arcABC operon is the only gene cluster regulated by ArgR, which is in contrast to the situation in many other bacteria. Reporter gene analysis with gfp under the control of the arcABC promoter demonstrated that ArgR is able to activate the arcABC promoter. Electrophoretic mobility shift assays with fragments of the arcABC promoter and recombinant ArgR, and chromatin immunoprecipitation with antibodies directed against ArgR, revealed that ArgR interacts with the arcABC promoter in vitro and in vivo by binding to a region from -147 to -72 bp upstream of the transcriptional start point. Overall, our results show that in S. suis, ArgR is an essential, system-specific transcriptional regulator of the ADS that interacts directly with the arcABC promoter in vivo.

  13. Effect of the selective pressure of sub-lethal level of heavy metals on the fate and distribution of ARGs in the catchment scale.

    Science.gov (United States)

    Xu, Yan; Xu, Jian; Mao, Daqing; Luo, Yi

    2017-01-01

    Our previous study demonstrated that high levels of antibiotic resistance genes (ARGs) in the Haihe River were directly attributed to the excessive use of antibiotics in animal agriculture. The antibiotic residues of the Xiangjiang River determined in this study were much lower than those of the Haihe River, but the relative abundance of 16 detected ARGs (sul1, sul2 and sul3, qepA, qnrA, qnrB, qnrD and qnrS, tetA, tetB, tetW, tetM, tetQ and tetO, ermB and ermC), were as high as the Haihe River particularly in the downstream of the Xiangjiang River which is close to the extensive metal mining. The ARGs discharged from the pharmaceutical wastewater treatment plant (PWWTP) are a major source of ARGs in the upstream of the Xiangjiang River. In the downstream, selective stress of heavy metals rather than source release had a significant influence on the distinct distribution pattern of ARGs. Some heavy metals showed a positive correlation with certain ARG subtypes. Additionally, there is a positive correlation between individual ARG subtypes and heavy metal resistance genes, suggesting that heavy metals may co select the ARGs on the same plasmid of antibiotic resistant bacteria. The co-selection mechanism between specific metal and antibiotic resistance was further confirmed by these isolations encoding the resistance genotypes to antibiotics and metals. To our knowledge, this is the first study on the fate and distribution of ARGs under the selective pressure exerted by heavy metals in the catchment scale. These results are beneficial to understand the fate, and to discern the contributors of ARGs from either the source release or the selective pressure by sub-lethal levels of environmental stressors during their transport on a river catchment scale. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Impaired 8-Hydroxyguanine Repair Activity of MUTYH Variant p.Arg109Trp Found in a Japanese Patient with Early-Onset Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Kazuya Shinmura

    2014-01-01

    Full Text Available Purpose. The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP, which is characterized by colorectal multiple polyps and carcinoma(s. However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients. Methods. Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing. Results. Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19*  MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19* and p.Arg109Trp corresponded to p.Arg5* and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5* is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays. Conclusion. These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19* and p.Arg109Trp MUTYH variants are associated with functional impairments.

  15. Role of αArg145 and βArg263 in the active site of penicillin acylase of Escherichia coli

    NARCIS (Netherlands)

    Alkema, Wynand B.L.; Prins, Antoon K.; de Vries, Erik; Janssen, Dick B.

    2002-01-01

    The active site of penicillin acylase of Eschcrichia coli contains two conserved arginine residues, The function of these arainines, alphaArg(145) and betaArg(263), was studied by site-directed mutagenesis and kinetic analysis of the mutant enzymes. The mutants alphaArg(145)-->Leu (alphaArg145Leu),

  16. A novel missense mutation, GGC(Arg454)→TGC(Cys), of CYP11B1 gene identified in a Chinese family with steroid 11β-hydroxylase deficiency

    Institute of Scientific and Technical Information of China (English)

    YE Zheng-qin; ZHANG Man-na; ZHANG Hui-jie; JIANG Jing-jing; LI Xiao-ying; ZHANG Ke-qin

    2010-01-01

    Background Steroid 11β-hydroxylase deficiency (11β-OHD), an autosomal recessive inherited disease, accounts for 5%-8% of congenital adrenal hyperplasia.It was scarcely reported in China.This article reports two Chinese girls with 11β-OHD.Methods The two patients were sisters and presented with hypertrichosis, skin pigmentation, laryngeal prominence and virilization of external genitalia.The patients were followed up for their clinical symptoms and signs, hormone profile,and adrenal image.The genomic deoxyribonucleic acids of the patients and their parents were isolated.11β-hydroxylase gene (CYP11B1) was amplified by polymerase chain reaction and directly sequenced.Results Hormone tests showed that serum cortisol was in the low limit of normal range, whereas the concentrations of adrenocorticotropic hormone, testosterone and progesterone were much higher than those of normal adult females.There were obvious adrenal hyperplasia and advance of bone age.After 11 months of treatment with dexamethasone,the skin pigment became regressed; the breast, uterus and ovary gradually developed and normal menstrual cycle started while the manifestations of virilization did not change.A single point mutation of CYP11B1 (R454C, GGC → TGC)in all the members of this family was detected.The sisters were homozygous and their parents were heterozygous.Conclusions The clinical manifestation of 11β-OHD is complicated.The manifestation of virilization could not regress after treatment with dexamethasone.The novel missense mutation of CYP11B1 (R454C, GGC → TGC) is the pathogenesis of 11β-OHD at least in some Chinese patients.

  17. 瘦素受体基因Lys109Arg多态性与慢性阻塞性肺疾病营养状况的关系%Study on Relationship between Leptin Receptor Gene Polymorphism Lys109Arg and Nutriture of Patients with Chronic Obstructive Pulmonary Disease

    Institute of Scientific and Technical Information of China (English)

    陈鹤峰; 李向阳; 朱汉民; 缪应新; 甘洁明; 洪慰麟

    2012-01-01

    目的:探讨瘦素受体基因Lys109Arg多态性与慢性阻塞性肺疾病营养状况的关系.对象与方法:观察159例 COPD稳定期患者及110例健康对照者体重指数(BMI)、理想体重百分比(NW%)、三头肌皮皱厚度(TSF)、上臂中点臂围(MAC)、血清白蛋白(ALB)、总淋巴细胞(LYM)等营养参数,将COPD组分为营养不良组(COPD1组)68例,COPD非营养不良组(COPD2组)91例.用酶联免疫吸附试验(ELISA)法测定血清瘦素水平,采用聚合酶链式反应及连接酶检测反应方法(PCR -LDR)测定瘦素受体Lys109Arg多态性的基因型.结果:COPD1组Lys 109Arg基因型GG、GA及从的频率分别为0.838、0.147和0.015,G和A等位基因分别为0.912和0.088; COPD2组Lys 109Arg基因型GG、GA及AA的频率分别为0.67、0.319和0.011,G和A等位基因分别为0.83和0.17;对照组Lys 109Arg基因型GG、GA及AA的频率分别为0.7、0.273和0.027,G和A等位基因分别 0.841和0.159;COPD1组Lys 109Arg基因型及等位基因频率与COPD2组和对照组比较差异有显著性;COPD2组和对照组比较差异无显著性.GG型受试者血清瘦素水平低于A/G型+AA型(39.08± 15.79ng/ml vs 43.29±17.25ng/ml),但差异无统计学意义.结论:瘦素受体基因Lys 109Arg多态性可能与COPD营养状况相关.%Objective: To investigate the association between Leptin Receptor Gene polymorphism Lys109Arg and nutriture of Patients with Chronic Obstructive Pulmonary Disease. Methods: A hundred and fifty-nine COPD patients in stable stage and a hundred and ten normal controls were studied. Nutritional parameters, including body mass index (BMT), percentage of normal body mass (NM%), triceps skin-fold thickness(TSF), mid-upper arm circumference(MAC), serum album(ALB), total lymphocyte counts(LYM) were determined. COPD patients were divided into malnutrition group (group I) and non-malnutrition group (group 2) according to the nutrition parameter. Serum leptin levels were measured by ELISA. The frequencies

  18. Study on the leptin receptor gene Gln223Arg polymorphism in patients with chronic obstructive pulmonary disease accompanied by malnutrition%慢性阻塞性肺疾病伴营养不良患者瘦素受体基因Gln223Arg多态性研究

    Institute of Scientific and Technical Information of China (English)

    陈鹤峰; 李向阳; 缪应新; 甘洁民; 洪慰麟; 周瑾

    2012-01-01

    目的 探讨瘦素受体基因Gln223Arg多态性与慢性阻塞性肺疾病伴营养不良的关系.方法 观察158例COPD临床稳定期老年患者及108例健康对照者,并根据体重指数(BMI)、理想体重百分比(NW%)、三头肌皮皱厚度(TSF)、上臂中点臂围(MAC)、血清白蛋白(ALB)、总淋巴细胞(LYM)等营养参数,将COPD组分为营养不良组(COPD1组)66例,COPD非营养不良组(COPD2组)92例.用酶联免疫吸附试验(ELISA)法测定血清瘦素水平,采用聚合酶链式反应及连接酶检测反应方法(PCR-LDR)测定158例COPD患者与108例对照组的瘦素受体基因Gln223Arg多态性的基因型.结果 COPD营养不良组Gln223Arg基因型GG、GA及从的频率分别为0.924、0.061和0.015,G和A等位基因频率分别为0.955和0.045; COPD非营养不良组Gln223Arg基因型GG、GA及AA的频率分别为0.783、0.206和0.011,G和A等位基因频率分别为0.886和0.114;对照组Gln223Arg基因型GG、GA及AA的频率分别为0.769、0.222和0.009,G和A等位基因频率分别0.88和0.12; COPD 1组Gln223Arg基因型及等位基因频率与COPD2组和对照组比较差异有显著性;COPD 2组和对照组比较差异无显著性.不同基因表型血清瘦素水平GG型低于A/G型+AA型(40.08+17.53 ng/mL vs 44.35±16.95 ng/mL),但差异无统计学意义.结论 瘦素受体基因Gln223Arg多态性可能与COPD营养不良有关.%Objective To investigate the relationship between leptin receptor gene Gln223Arg polymorphism and malnutrition of patients with chronic obstructive pulmonary disease (COPD). Methods 158 elderly patients wilh COPD in stable stage and 10S normal controls were studied. Nutritional parameters, including body mass index (BMI), percentage of normal body mass (NM%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), serum album (ALB), total lymphocyte counts (LYM) in all cases, were evaluated, respectively. COPD patients were divided into malnutrition group (group 1) and non

  19. The Effect of the Arg389Gly Beta-1 Adrenoceptor Polymorphism on Plasma Renin Activity and Heart Rate and the Genotype-Dependent Response to Metoprolol Treatment

    DEFF Research Database (Denmark)

    Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen

    2012-01-01

    A gene-drug interaction has been indicated between beta-1 selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). We studied the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR) and the genotype......(metoprolol concentration) varied significantly between genotypes (P = 0.024). In Gly/Gly subjects, PRA decreased significantly with metoprolol concentration before (P = 0.025) and after exercise (P effect on PRA. The effect of metoprolol concentration...... on PRA in Gly/Gly subjects was enhanced by exercise (P = 0.044). No significant differences in HR were seen between genotype groups. Resting PRA was lower in Gly/Gly than in Arg/Arg subjects, and the effect of exercise and metoprolol concentration on PRA was stronger in Gly/Gly subjects than...

  20. Effect of the Arg389Gly β₁-adrenoceptor polymorphism on plasma renin activity and heart rate, and the genotype-dependent response to metoprolol treatment.

    Science.gov (United States)

    Petersen, Morten; Andersen, Jon T; Jimenez-Solem, Espen; Broedbaek, Kasper; Hjelvang, Brian R; Henriksen, Trine; Frandsen, Erik; Forman, Julie L; Torp-Pedersen, Christian; Køber, Lars; Poulsen, Henrik E

    2012-09-01

    1. A gene-drug interaction has been indicated between β₁-adrenoceptor-selective beta-blockers and the Arg389Gly polymorphism (rs1801253) in the adrenergic beta-1 receptor gene (ADRB1). In the present study, we investigated the effect of the ADRB1 Arg389Gly polymorphism on plasma renin activity (PRA) and heart rate (HR), as well as genotype-dependent responses to metoprolol and exercise. 2. Twenty-nine healthy male subjects participated in two treatment periods (placebo and 200 mg/day metoprolol). A 15 min submaximal exercise test was performed after each treatment period and PRA and HR were measured before and after exercise. 3. Before exercise, median PRA was lower in Gly/Gly subjects than in Arg/Arg subjects after both placebo (P = 0.030) and metoprolol (P = 0.020) treatment. After placebo, the exercise-induced increase in PRA was greater in Gly/Gly than Arg/Gly and Arg/Arg subjects (P = 0.033). The linear association between log(PRA) and log(metoprolol concentration) varied significantly between genotypes (P = 0.024). In Gly/Gly subjects, PRA decreased significantly with metoprolol concentration before (P = 0.025) and after exercise (P concentration had no effect on PRA. The effect of metoprolol concentration on PRA in Gly/Gly subjects was enhanced by exercise (P = 0.044). No significant differences in HR were seen between genotype groups. 4. Resting PRA was lower in Gly/Gly than Arg/Arg subjects and the effect of exercise and metoprolol concentration on PRA was stronger in Gly/Gly subjects than with the other two genotypes. Thus, Gly/Gly heart failure patients may require lower doses of metoprolol than other patients to block neurohumoral hyperactivity.

  1. Cloning and Expression Analyses of γGCS Gene in Hevea brasiliensis Muell.Arg.%巴西橡胶树HbγGCS基因克隆及表达分析

    Institute of Scientific and Technical Information of China (English)

    邓治; 刘向红; 覃碧; 李德军

    2012-01-01

    γ-Glutamylcysteine synthetase (yGCS) is a rate-limiting enzyme in glutathione biosynthesis. Gluta-thione plays a key role in many important physiological processes of plant. In this study, a full-length cDNA sequence of yGCS gene was obtained from the latex of Hevea brasiliensis with degeneracy PCR and RACE, and named as HbyGCS (GenBank accession No. GU997638). The full length cDNA of HbyGCS was 2 187 bp in size, with a 1 572-bp open reading frame encoding a deduced polypeptide of 523 amino acids. The phylogenetic analyses indicated that HbyGCS belonged to the yGCS of dicot subclass. Vitis vinifera yGCS and HbyGCS were divided into one group. Compared with the monocot yGCSs, HbyGCS indicated closer phylogenetic relationship with dicot yGCSs. Semi-quantitative RT-PCR analysis indicated that HbyGCS was ubiquitously expressed in all tissues, with the highest expression in flowers. HbyGCS transcript level was significantly higher in latex of healthy rubber trees than tapping panel dryness (TPD) ones. The expression of HbyGCS was regulated by ethylene, jasmonic acid, H2O2, mechanical wounding, drought, low temperature and NaCl treatments.%γ-谷氨酰半胱氨酸合成酶(γGCS)是细胞内谷胱甘肽(GSH)生物合成的限速酶,GSH在植物许多生理过程中发挥重要作用.本研究采用简并PCR和RACE技术获得巴西橡胶树γGCS基因全长cDNA序列,命名为HbγGCS (GenBank登录号:GU997638).该基因全长2187 bp,最长开放阅读框为1572 bp,编码523个氨基酸.进化分析结果表明HbγGCS属双子叶植物γGCS亚类,同葡萄γGCS分为一组,与单子叶植物的亲缘关系较远.半定量RT-PCR结果表明HbγGCS基因在胶乳、叶片、树皮、花中均有表达,以花中表达量最大.健康橡胶树胶乳中HbγGCS表达量高于死皮树.HbγGCS表达受乙烯、茉莉酸、过氧化氢、机械伤害、干旱、低温和高盐调控.

  2. Co-Expression of Wild-Type P2X7R with Gln460Arg Variant Alters Receptor Function.

    Directory of Open Access Journals (Sweden)

    Fernando Aprile-Garcia

    Full Text Available The P2X7 receptor is a member of the P2X family of ligand-gated ion channels. A single-nucleotide polymorphism leading to a glutamine (Gln by arginine (Arg substitution at codon 460 of the purinergic P2X7 receptor (P2X7R has been associated with mood disorders. No change in function (loss or gain has been described for this SNP so far. Here we show that although the P2X7R-Gln460Arg variant per se is not compromised in its function, co-expression of wild-type P2X7R with P2X7R-Gln460Arg impairs receptor function with respect to calcium influx, channel currents and intracellular signaling in vitro. Moreover, co-immunoprecipitation and FRET studies show that the P2X7R-Gln460Arg variant physically interacts with P2X7R-WT. Specific silencing of either the normal or polymorphic variant rescues the heterozygous loss of function phenotype and restores normal function. The described loss of function due to co-expression, unique for mutations in the P2RX7 gene so far, explains the mechanism by which the P2X7R-Gln460Arg variant affects the normal function of the channel and may represent a mechanism of action for other mutations.

  3. FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients.

    Science.gov (United States)

    Streit, S; Mestel, D S; Schmidt, M; Ullrich, A; Berking, C

    2006-06-19

    A single nucleotide polymorphism in the gene for FGFR4 (-Arg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P = 0.023 and AJCC, P = 0.046), presence of microulceration (P = 0.009), tumour vascularity (P = 0.001), metastases (P = 0.025), number of primary tumours (P = 0.022), overall survival (P = 0.047) and disease-free survival (P = 0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P = 0.004) and by Breslow in mm (P = 0.02)) and the tumour subtype nodular melanoma (P = 0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma.

  4. Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Torekov, Signe S; Larsen, Lesli H; Glümer, Charlotte

    2005-01-01

    tolerance test (OGTT) (P = 0.03), an increased area under the curve for the post-OGTT plasma glucose level (P = 0.03), and a lower insulinogenic index (P = 0.01). In conclusion, the common Arg allele of the PYY Arg72Thr variant modestly associates with type 2 diabetes and with type 2 diabetes......We tested the hypothesis that variants in the gene encoding the prepropeptide YY (PYY) associate with type 2 diabetes and/or obesity. Mutation analyses of DNA from 84 patients with obesity and familial type 2 diabetes identified two polymorphisms, IVS3 + 68C>T and Arg72Thr, and one rare variant......, +151C>A of PYY. The common allele of the Arg72Thr variant associated with type 2 diabetes with an allele frequency of the Arg allele of 0.667 (95% CI 0.658-0.677) among 4,639 glucose-tolerant subjects and 0.692 (0.674-0.710) among 1,326 patients with type 2 diabetes (P = 0.005, odds ratio 1.19 [95% CI...

  5. FGFR4 Gly388Arg polymorphism contributes to prostate cancer development and progression: A meta-analysis of 2618 cases and 2305 controls

    Directory of Open Access Journals (Sweden)

    Zhang Zheng D

    2011-02-01

    Full Text Available Abstract Background Fibroblast growth factor receptor 4 (FGFR4 displays multiple biological activities, including mitogenic and angiogenic activity, and plays important roles in the etiology and progression of prostate cancer. Gly388Arg polymorphism in FGFR4 gene has been reported to be involved in prostate cancer incidence and aggressiveness in several studies. To derive a more precise estimation of the relationship, a meta-analysis was performed. Methods Odds ratios (ORs with 95% confidence intervals (CIs were estimated to assess the association. Results The Arg388 allele increased prostate cancer risk compared with Gly388 allele (OR = 1.17, 95% CI = 1.07-1.29. When stratified by race, there was a significantly increased prostate cancer risk in Asian and Caucasian populations. Moreover, prostate cancer patients with Arg/Arg genotype had a 1.34-fold increased risk of advanced prostate cancer (95% CI: 1.03-1.74 compared with those with Gly/Gly+Gly/Arg genotype. Conclusion This meta-analysis showed the evidence that FGFR4 Gly388Arg polymorphism was associated with an increased risk of prostate cancer development and progression, suggesting that FGFR4 Gly388Arg polymorphism could be a marker for prostate cancer development and progression.

  6. KIF6 719Arg Carrier Status Association with Homocysteine and C-Reactive Protein in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease Patients

    Directory of Open Access Journals (Sweden)

    Michael Malek-Ahmadi

    2013-01-01

    Full Text Available Recent research has demonstrated associations between statin use, KIF6 719Arg carrier status, and cholesterol levels and amnestic mild cognitive impairment (aMCI and Alzheimer’s disease (AD patients. The association between 719Arg carrier status with homocysteine (tHcy and c-reactive protein (CRP levels in aMCI and AD has not been previously investigated. Data from 175 aMCI and AD patients were used for the analysis. 719Arg carriers had significantly lower levels of tHcy than noncarriers (P=0.02. No significant difference in CRP levels between 719Arg carriers and noncarriers was present (P=0.37. Logistic regression yielded no significant effect for 719Arg status on CRP [OR = 1.79 (0.85, 3.83, P=0.13] but did demonstrate a significant effect for tHcy [OR = 0.44 (0.23, 0.83, P=0.01] after adjusting for ApoE ε4 carrier status, age, gender, and statin use. This study is the first to explore the relationship between KIF6 719Arg carrier status with tHcy and CRP levels. 719Arg carriers were more likely to have normal tHcy levels after adjusting for ApoE ε4 status, age, gender, and statin use. These results suggest that the KIF6 gene might influence cardiovascular pathways associated with AD.

  7. A novel pro-Arg motif recognized by WW domains.

    Science.gov (United States)

    Bedford, M T; Sarbassova, D; Xu, J; Leder, P; Yaffe, M B

    2000-04-07

    WW domains mediate protein-protein interactions through binding to short proline-rich sequences. Two distinct sequence motifs, PPXY and PPLP, are recognized by different classes of WW domains, and another class binds to phospho-Ser-Pro sequences. We now describe a novel Pro-Arg sequence motif recognized by a different class of WW domains using data from oriented peptide library screening, expression cloning, and in vitro binding experiments. The prototype member of this group is the WW domain of formin-binding protein 30 (FBP30), a p53-regulated molecule whose WW domains bind to Pro-Arg-rich cellular proteins. This new Pro-Arg sequence motif re-classifies the organization of WW domains based on ligand specificity, and the Pro-Arg class now includes the WW domains of FBP21 and FE65. A structural model is presented which rationalizes the distinct motifs selected by the WW domains of YAP, Pin1, and FBP30. The Pro-Arg motif identified for WW domains often overlaps with SH3 domain motifs within protein sequences, suggesting that the same extended proline-rich sequence could form discrete SH3 or WW domain complexes to transduce distinct cellular signals.

  8. Effect of β3-adrenergic receptor gene Trp64Arg polymorphism on uric acid levels in a Chinese male type 2 diabetes mellitus population%β3肾上腺素受体基因Trp64Arg多态性与中国男性2型糖尿病患者合并高尿酸血症的相关性研究

    Institute of Scientific and Technical Information of China (English)

    黄琼; 张留福; 程雁; 司力; 魏伟

    2013-01-01

    目的:探讨中国人群男性2型糖尿病患者中β3肾上腺素受体基因Trp64Arg多态性与高尿酸血症的相关性.方法:196名高尿酸血症的2型糖尿病患者和196名正常尿酸水平的2型糖尿病患者进行基因分型.检测体重指数、腰臀比、收缩压、舒张压、血尿酸、肌酐、尿素氮、甘油三酯、低密度脂蛋白胆固醇脂、高密度脂蛋白胆固醇脂、空腹血糖和餐后血糖的水平.结果:高尿酸血症组中,携带不同β3肾上腺素受体Trp64Arg基因型的2型糖尿病患者其尿酸水平有统计学差异,且呈基因剂量效应[CC组(599.53±113.70) vs CT组(529.78±81.10) vs TT组(507.33±74.27),P<0.01].在该研究中,Trp64Arg TC+CC基因型患者的血尿酸水平亦显著高于TT基因型组p(557.95±99.91) vs (503.47±69.40) μmol/L,P<0.01].结论:β3肾上腺素受体基因Trp64Arg多态性与2型糖尿病合并高尿酸血症的具有相关性.%AIM:To investigate the association of β3-adrenergic receptor gene Trp64Arg polymorphism with hyperuricemia in a Chinese male type 2 diabetes mellitus patients population.METHODS:196 hyperuricemic and 196 normouricemic male subjects were genotyped in this study.Body mass index (BMI),waist to hip ratio (WHR),systolic blood pressure (SBP),diastolic blood pressure (DBP),serum uric acid,urea nitrogen,creatinine,triglyceride,total cholesterol,low-density lipoprotein-cholesterol (LDL-C),high-density lipoprotein-cholesterol (HDL-C),fasting plasma glucose (FPG),postprandial plasma glucose (PPG) were detected.RESULTS:We found patients with different Trp64Arg genotype showed significant differences in average uric acid concentrations (599.53±113.70 vs 529.78±81.10 vs 507.33±74.27,P<0.01) among CC,CT and TT genotype and there were significantly higher average uric acid concentrations in Trp64Arg TC + CC genotype individuals (557.95 ± 99.91 vs 503.47 ± 69.40 μ mol/L,P < 0.01) than those TT genotype subjects in the hyperuricemic group

  9. ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis.

    Science.gov (United States)

    Zhang, Guohong; Mai, Ruiqin; Huang, Bo

    2010-10-27

    Incidence of Esophageal squamous cell carcinoma (ESCC) is prevalent in Asian populations, especially in the ones from the "Asian esophageal cancer belt" along the Silk Road and the ones from East Asia (including Japan). Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984) polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians. This polymorphism was identified as responsible for susceptibility in the first large-scale genome-wide association study of ESCC and that's explained by its modulation of alcohol oxidization capability. To investigate the association of ADH1B Arg47His with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis. A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2 Glu504Lys. Heterogeneity among studies and their publication bias were also tested. The ADH1B*47Arg allele was found to be associated to increased risk of ESCC, with the odds ratios (OR) being 1.62 (95% CI: 1.49-1.76) and 3.86 (2.96-5.03) for the His/Arg and the Arg/Arg genotypes, respectively. When compared with the His/His genotype of non-drinkers, the Arg/Arg genotype can interact with alcohol drinking and greatly increase the risk of ESCC (OR = 20.69, 95%CI: 5.09-84.13). Statistical tests also showed gene-gene interaction of ADH1B Arg+ with ALDH2 Lys+ can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32-78.07). Revealed by this meta-analysis, ADH1B*47Arg as a common ancestral allele can significantly increase the risk of ESCC in Asians, especially when coupled with alcohol drinking or the ALDH2*504Lys allele.

  10. ADH1B Arg47His polymorphism is associated with esophageal cancer risk in high-incidence Asian population: evidence from a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Guohong Zhang

    Full Text Available BACKGROUND AND OBJECTIVES: Incidence of Esophageal squamous cell carcinoma (ESCC is prevalent in Asian populations, especially in the ones from the "Asian esophageal cancer belt" along the Silk Road and the ones from East Asia (including Japan. Silk Road and Eastern Asia population genetics are relevant to the ancient population migration from central China. The Arg47His (rs1229984 polymorphism of ADH1B is the highest in East Asians, and ancient migrations along the Silk Road were thought to be contributive to a frequent ADH1B*47His allele in Central Asians. This polymorphism was identified as responsible for susceptibility in the first large-scale genome-wide association study of ESCC and that's explained by its modulation of alcohol oxidization capability. To investigate the association of ADH1B Arg47His with ESCC in Asian populations under a common ancestry scenario of the susceptibility loci, we combined all available studies into a meta-analysis. METHODS: A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2 Glu504Lys. Heterogeneity among studies and their publication bias were also tested. RESULTS: The ADH1B*47Arg allele was found to be associated to increased risk of ESCC, with the odds ratios (OR being 1.62 (95% CI: 1.49-1.76 and 3.86 (2.96-5.03 for the His/Arg and the Arg/Arg genotypes, respectively. When compared with the His/His genotype of non-drinkers, the Arg/Arg genotype can interact with alcohol drinking and greatly increase the risk of ESCC (OR = 20.69, 95%CI: 5.09-84.13. Statistical tests also showed gene-gene interaction of ADH1B Arg+ with ALDH2 Lys+ can bring more risk to ESCC (OR  = 13.46, 95% CI: 2.32-78.07. CONCLUSION: Revealed by this meta-analysis, ADH1B*47Arg as a common ancestral allele can significantly increase the risk of ESCC in Asians, especially when coupled

  11. Neovascularization and functional recovery after intracerebral hemorrhage is conditioned by the Tp53 Arg72Pro single-nucleotide polymorphism.

    Science.gov (United States)

    Rodríguez, Cristina; Sobrino, Tomás; Agulla, Jesús; Bobo-Jiménez, Verónica; Ramos-Araque, María E; Duarte, Juan J; Gómez-Sánchez, José C; Bolaños, Juan P; Castillo, José; Almeida, Ángeles

    2017-01-01

    Intracerebral hemorrhage (ICH) is a devastating subtype of stroke that lacks effective therapy and reliable prognosis. Neovascularization following ICH is an essential compensatory response that mediates brain repair and modulates the clinical outcome of stroke patients. However, the mechanism that dictates this process is unknown. Bone marrow-derived endothelial progenitor cells (EPCs) promote endothelial repair and contribute to ischemia-induced neovascularization. The human Tp53 gene harbors a common single-nucleotide polymorphism (SNP) at codon 72, which yields an arginine-to-proline amino-acidic substitution (Arg72Pro) that modulates the apoptotic activity of the p53 protein. Previously, we found that this SNP controls neuronal susceptibility to ischemia-induced apoptosis in vitro. Here, we evaluated the impact of the Tp53 Arg72Pro SNP on vascular repair and functional recovery after ICH. We first analyzed EPC mobilization and functional outcome based on the modified Rankin scale scores in a hospital-based cohort of 78 patients with non-traumatic ICH. Patients harboring the Pro allele of the Tp53 Arg72Pro SNP showed higher levels of circulating EPC-containing CD34(+) cells, EPC-mobilizing cytokines - vascular endothelial growth factor and stromal cell-derived factor-1α - and good functional outcome following ICH, when compared with the homozygous Arg allele patients, which is compatible with increased neovascularization. To assess directly whether Tp53 Arg72Pro SNP regulated neovascularization after ICH, we used the humanized Tp53 Arg72Pro knock-in mice, which were subjected to the collagenase-induced ICH. The brain endothelial cells of the Pro allele-carrying mice were highly resistant to ICH-mediated apoptosis, which facilitated cytokine-mediated EPC mobilization, cerebrovascular repair and functional recovery. However, these processes were not observed in the Arg allele-carrying mice. These results reveal that the Tp53 Arg72Pro SNP determines

  12. Antibiotic resistance genes in the environment

    Directory of Open Access Journals (Sweden)

    Jianqiang Su

    2013-07-01

    Full Text Available Antibiotic resistance and its spread in bacteria are topics of great importance in global research. In this paper, we review recent progress in understanding sources, dissemination, distribution and discovery of novel antibiotics resistance genes (ARGs in the environment. Bacteria exhibiting intrinsic resistance and antibiotic resistant bacteria in feces from humans and animals are the major sources of ARGs occurring in the environment. A variety of novel ARGs have been discovered using functional metagenomics. Recently, the long-term overuse of antibotics in drug therapy and animal husbandry has led to an increase in diversity and abundance of ARGs, causing the environmental dissemination of ARGs in aquatic water, sewage treatmentplants, rivers, sediment and soil. Future research should focus on dissemination mechanisms of ARGs, the discovery of novel ARGs and their resistant mechanisms, and the establishment of environmental risk assessment systems for ARGs.

  13. Hepatic fibrinogen storage disease due to the fibrinogen γ375 Arg → Trp mutation "fibrinogen aguadilla" is present in Arabs

    Directory of Open Access Journals (Sweden)

    Abdulrahman Al-Hussaini

    2014-01-01

    Full Text Available The mutation γ375Arg → Trp (fibrinogen Aguadilla is one of four mutations (Brescia, Aguadilla, Angers, and AI duPont capable of causing hepatic storage of fibrinogen. It has been observed in four children from the Caribbean, Europe, and Japan, suffering from cryptogenic liver disease. We report the first case of hepatic fibrinogen storage disease in Arabs due to a mutation in the fibrinogen γ-chain gene in a 3-year-old Syrian girl presenting with elevated liver enzymes. The finding of an impressive accumulation of fibrinogen in liver cells raised the suspicion of endoplasmic reticulum storage disease. Sequencing of the fibrinogen genes revealed a γ375Arg → Trp mutation (fibrinogen Aguadilla in the child and in her father. In conclusion, when confronted with chronic hepatitis of unknown origin, one should check the plasma fibrinogen level and look carefully for the presence of hepatocellular intracytoplasmic globular inclusions to exclude hepatic fibrinogen storage disease.

  14. Effects of endogenous nitric oxide induced by 5-fluorouracil and L-Arg on liver carcinoma in nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To study the effects of endogeous nitric oxide induced by 5-fluorouracil (5-FU) and L-arginine (L-Arg)on the human liver carcinoma model in nude mice.METHODS: The human liver carcinoma model in nude mice was established with BEL-7402 cells and normal saline (NS), 5-FU and 5-FU + L-Arg injected intraperitoneally. The tumor size was measured. The necrotic degree and range were observed under microscope. The apoptosis of cancer cell was detected by turmina deoxynucleotidyl transferanse mediated dUTP nick end labeling (TUNEL) method. Immunohistochemical method was performed to determine the expression of iNOS, P16, BAX. The chemical colorimetry was used to test the activity and nitrate reductase method was adopted to test the concentration of nitric oxide (NO) in the tumor tissue. The BI2000 pathological image analyzer was used to analyze the result of immunohistochemistry.RESULTS: 5-FU combined with L-Arg could inhibit the tumor growth apparently. In NS, 5-FU and 5-FU+L-Arg groups, the changes of tumor volumes were 257.978 ± 59.0, 172.232 ± 66.0 and 91.523 ± 26.7 mm3,respectively (P < 0.05 5-FU vs 5-FU + L-Arg group;P < 0.05 NS vs 5-FU + L-Arg group; P < 0.05, NS vs 5-FU group).The necrotic range and apoptosis index were significantly increased after the drug injection. The necrotic range was biggest in 5-FU + L-Arg group (x2 = 15.963, P < 0.05).The apoptosis indexes were as follows: NS, 17.4% ± 6.19%; 5-FU, 31.3% ± 12.3%; and 5-FU + L-Arg, 46% ± 15.24% (P < 0.05, 5-FU vs 5-FU + L-Arg; P < 0.05, NS vs 5-FU + L-Arg; P < 0.05, NS vs 5-FU). The expression and activity of iNOS were increased in the tumor tissue.The concentration of NO was also increased. F of optical density of iNOS, iNOS activity and NO concentration are 31.693, 21.949, and 33.909, respectively, P < 0.05. The concentration of NO was related to the expression of P16 and BAX. The correlation coefficient was 0.764 and 0.554.CONCLUSION: 5-FU combined with L-Arg can inhibit the

  15. β1-adrenergic receptor(Arg389Gly) polymorphism and response to bisoprolol in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    俞文萍

    2006-01-01

    Objective The purpose of this study was to investigate the relation between the Arg389Gly polymorphism of theβ1-AR gene and chronic heart failure (CHF) and to evaluate the effect of this polymorphism on clinical response toβ-adrenoceptor blockade (bisoprolol) in patients with CHF. Methods One hundred and ten patients with stable CHF receiving basic therapy for heart failure were included. Before initiation and 3 months af-

  16. Characterisation of a C1qtnf5 Ser163Arg knock-in mouse model of late-onset retinal macular degeneration.

    Directory of Open Access Journals (Sweden)

    Xinhua Shu

    Full Text Available A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse "knock-in" model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct.

  17. Association analysis of the beta-3 adrenergic receptor Trp64Arg (rs4994) polymorphism with urate and gout.

    Science.gov (United States)

    Fatima, Tahzeeb; Altaf, Sara; Phipps-Green, Amanda; Topless, Ruth; Flynn, Tanya J; Stamp, Lisa K; Dalbeth, Nicola; Merriman, Tony R

    2016-02-01

    The Arg64 allele of variant rs4994 (Trp64Arg) in the β3-adrenergic receptor gene has been associated with increased serum urate and risk of gout. Our objective was to investigate the relationship of rs4994 with serum urate and gout in New Zealand European, Māori and Pacific subjects. A total of 1730 clinically ascertained gout cases and 2145 controls were genotyped for rs4994 by Taqman(®). Māori and Pacific subjects were subdivided into Eastern Polynesian (EP) and Western Polynesian (WP) sample sets. Publicly available genotype data from the Atherosclerosis Risk in Communities Study and the Framingham Heart Study were utilized for serum urate association analysis. Multivariate logistic and linear regression adjusted for potential confounders was carried out using R version 2.15.2. No significant association of the minor Arg64 (G) allele of rs4994 with gout was found in the combined Polynesian cohorts (OR = 0.98, P = 0.88), although there was evidence, after adjustment for renal disease, for association in both the WP (OR = 0.53, P = 0.03) and the lower Polynesian ancestry EP sample sets (OR = 1.86, P = 0.05). There was no evidence for association with gout in the European sample set (OR = 1.11, P = 0.57). However, the Arg64 allele was positively associated with urate in the WP data set (β = 0.036, P = 0.004, P Corrected = 0.032). Association of the Arg64 variant with increased urate in the WP sample set was consistent with the previous literature, although the protective effect of this variant with gout in WP was inconsistent. This association provides an etiological link between metabolic syndrome components and urate homeostasis.

  18. XRCC1 genetic polymorphism Arg399Gln and hepatocellular carcinoma risk: a meta-analysis.

    Science.gov (United States)

    Liu, Fei; Li, Bo; Wei, Yonggang; Yan, Lvnan; Wen, Tianfu; Zhao, Jichun; Xu, Mingqing

    2011-07-01

    Studies investigating the association between X-ray repair cross-complementing group 1 (XRCC1) genetic polymorphism Arg399Gln and hepatocellular carcinoma (HCC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline, Embase, CNKI and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for XRCC1 polymorphism and HCC were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate. The pooled ORs were performed for a codominant model (Gln/Gln vs. Arg/Arg, Arg/Gln vs. Arg/Arg), a dominant model (Gln/Gln+Arg/Gln vs. Arg/Arg) and a recessive model (Gln/Gln vs. Arg/Gln+Arg/Arg). This meta-analysis included 11 case-control studies, which included 2208 HCC cases and 3265 controls. Overall, the variant genotypes (Gln/Gln and Arg/Gln) of Arg399Gln were not associated with HCC risk when compared with the wild-type Arg/Arg homozygote (Gln/Gln vs. Arg/Arg, OR=1.01, 95% CI=0.79-1.28; Arg/Gln vs. Arg/Arg, OR=1.09, 95% CI=0.81-1.45). Similarly, no associations were found in the dominant and recessive models (dominant model, OR=1.12, 95% CI=0.85-1.47; recessive model, OR=0.99, 95% CI=0.79-1.25). Limiting the analysis to the studies within Hardy-Weinberg equilibrium, the results were persistent and robust. When stratifying for ethnicity, country/region and source of controls, no evidence of a significant association was observed in any subgroup. No publication bias was found in the present study. No association is found between the XRCC1 polymorphism Arg399Gln and the risk of HCC. © 2011 John Wiley & Sons A/S.

  19. Influence of angiotensin converting enzyme gene insertion/deletion polymorphism and β3-adrenergic receptor gene Trp64Arg polymorphism on fetal growth and neonatal insulin sensitivity%血管紧张素转化酶基因插入/缺失多态性及β3肾上腺素能受体基因Trp64Arg多态性对胎儿宫内发育及新生儿胰岛素敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    崔蕴璞; 韩彤妍; 王新利; 叶鸿瑁

    2008-01-01

    Objective To understand the influence of angiotensin converting enzyme(ACE)gene insertion/deletion(I/D)polymorphism and β3-adrenergic receptor(β3-AR)gene Trp64Arg polymorphism on fetal growth and neonatal insulin sensitivity.Methods Totally 296 newborn infants were selected into our study and divided into 2 groups according to gestational age and birth weight:adequate-for-gestationalage(AGA)group(222 cases)and small-for-gestational-age(SGA)group(74 case).Serum glucose and insulin were examined in the morning of the 3rd day before milk.Insulin sensitivity was evaluated by homeostasis model assessment(HOMA)equation.β3-AR gene Trp64Arg polymorphism and ACE gene I/D polymorphism(202 cases)were analysed using polymerase chain reaction-restricted fragment length polymorphism(PCR-RFLP)technique.Gestational age,birth weight,birth weight percentage,serum glucose,insulin and HOMA-IR were compared among different genotype groups.Statistical analysis was performed with the SPSS 10.0 software.Results No significant difference was found between the sernm glucose level of SGA group(4.03±1.05 mmol/L)and AGA group(4.05±1.14 mmol/L),P=0.008. The serum insulin level(converted into Ln)of SGA group(2.262±0.746)was significantly higher than that of AGA group(1.757±0.805),P<0.001.The HOMA-IR(also convened into Ln)level of SGA group(0.217±0.367)was also significantly higher than that of AGA group(0.001±0.378),P<0.001. In the SGA group β3-AR gene Arg64 allele carriers had higher serum insulin and HOMA-IR level(botll changed to Ln,2.654±0.701,0.371±0.338)compared with noncarriers(2.074±0.698,0.143± O.360),P<0.05.The ACE gene DD genotype carriers had higher serum insulin and HOMA-IR level(both were converted into Ln,2.19 4-0.91,0.5l 4-1.01)compared with II(1.77 ±0.85,0.02 ±0.93) and ID genotype group(1.77 ±0.83,0.05 ±0.91),P<0.05.The ACE gene DD carriers had lower birth weight percentage compared with II and ID genotype group.P<0.05.When both genes'polymorphisms were taken

  20. A novel distinctive cerebrovascular phenotype is associated with heterozygous Arg179 ACTA2 mutations

    Science.gov (United States)

    Munot, Pinki; Saunders, Dawn E.; Milewicz, Dianna M.; Regalado, Ellen S.; Ostergaard, John R.; Braun, Kees P.; Kerr, Timothy; Lichtenbelt, Klaske D.; Philip, Sunny; Rittey, Christopher; Jacques, Thomas S.; Cox, Timothy C.

    2012-01-01

    Mutations in the ACTA2 gene lead to diffuse and diverse vascular diseases; the Arg179His mutation is associated with an early onset severe phenotype due to global smooth muscle dysfunction. Cerebrovascular disease associated with ACTA2 mutations has been likened to moyamoya disease, but appears to have distinctive features. This study involved the analysis of neuroimaging of 13 patients with heterozygous missense mutations in ACTA2 disrupting Arg179. All patients had persistent ductus arteriosus and congenital mydriasis, and variable presentation of pulmonary hypertension, bladder and gastrointestinal problems associated with this mutation. Distinctive cerebrovascular features were dilatation of proximal internal carotid artery, occlusive disease of terminal internal carotid artery, an abnormally straight course of intracranial arteries, and absent basal ‘moyamoya’ collaterals. Patterns of brain injury supported both large and small vessel disease. Key differences from moyamoya disease were more widespread arteriopathy, the combination of arterial ectasia and stenosis and, importantly, absence of the typical basal ‘moyamoya’ collaterals. Evaluation of previously published cases suggests some of these features are also seen in the ACTA2 mutations disrupting Arg258. The observation that transition from dilated to normal/stenotic arterial calibre coincides with where the internal carotid artery changes from an elastic to muscular artery supports the hypothesis that abnormal smooth muscle cell proliferation caused by ACTA2 mutations is modulated by arterial wall components. Patients with persistent ductus arteriosus or congenital mydriasis with a label of ‘moyamoya’ should be re-evaluated to ensure the distinctive neuroimaging features of an ACTA2 mutation have not been overlooked. This diagnosis has prognostic and genetic implications, and mandates surveillance of other organ systems, in particular the aorta, to prevent life-threatening aortic dissection

  1. Leptin receptor Gln223Arg polymorphism and breast cancer risk in Nigerian women: A case control study

    Directory of Open Access Journals (Sweden)

    Anyanwu Stanley N

    2008-11-01

    Full Text Available Abstract Background Leptin, a 16 kDa polypeptide hormone, implicated in various physiological processes, exerts its action through the leptin receptor, a member of the class I cytokine receptor family. Both leptin and leptin receptor have recently been implicated in processes leading to breast cancer initiation and progression in animal models and humans. An A to G transition mutation in codon 223 in exon 6 of the leptin receptor gene, resulting in glutamine to arginine substitution (Gln223Arg, lies within the first of two putative leptin-binding regions and may be associated with impaired signaling capacity of the leptin receptor. This study was designed to assess the role of this polymorphism in breast cancer susceptibility in Nigerian women. Methods We utilized a polymerase chain reaction (PCR-based restriction fragment length polymorphism (RFLP assay to evaluate the association between the Gln223Arg polymorphism of the leptin receptor gene and breast risk in Nigeria in a case control study involving 209 women with breast cancer and 209 controls without the disease. Study participants were recruited from surgical outpatient clinics and surgical wards of four University Teaching Hospitals located in Midwestern and southeastern Nigeria between September 2002 and April 2004. Results Premenopausal women carrying at least one LEPR 223Arg allele were at a modestly increased risk of breast cancer after adjusting for confounders (OR = 1.8, 95% confidence interval [CI] 1.0–3.2, p = 0.07. There was no association with postmenopausal breast cancer risk (OR = 0.9, 95% CI 0.4–1.8, p = 0.68. Conclusion Our results suggest that the LEPR Gln223Arg polymorphism in the extracellular domain of the LEPR receptor gene is associated with a modestly increased risk of premenopausal breast cancer in Nigerian women.

  2. Tiotropium is noninferior to salmeterol in maintaining improved lung function in B16-Arg/Arg patients with asthma.

    Science.gov (United States)

    Bateman, Eric D; Kornmann, Oliver; Schmidt, Peter; Pivovarova, Anna; Engel, Michael; Fabbri, Leonardo M

    2011-08-01

    The efficacy and safety of inhaled long-acting β(2)-adrenergic agonists in asthmatic patients with the B16-Arg/Arg genotype has been questioned, and the use of antimuscarinics has been proposed as an alternative in patients whose symptoms are not controlled by inhaled corticosteroids (ICSs). We compared the efficacy and safety of the long-acting anticholinergic tiotropium with salmeterol and placebo added to an ICS in B16-Arg/Arg patients with asthma that was not controlled by ICSs alone. In a double-blind, double-dummy, placebo-controlled trial, after a 4-week run-in period with 50 μg of twice-daily salmeterol administered through a metered-dose inhaler, 388 asthmatic patients were randomized 1:1:1 to 16 weeks of treatment with 5 μg of Respimat tiotropium administered daily in the evening, 50 μg of salmeterol administered twice daily through a metered-dose inhaler, or placebo. Patients aged 18 to 67 years demonstrated reversibility to bronchodilators, and their symptoms were uncontrolled by regular ICSs (400-1000 μg of budesonide/equivalent). ICS regimens were maintained throughout the trial. The mean weekly morning peak expiratory flow (PEF) before randomization was 358 ± 115.7 L/min (range, 80.3-733.0 L/min). Changes in weekly PEF from the last week of the run-in period to the last week of treatment (primary end point: change in PEF) were -3.9 ± 4.87 L/min (n = 128) for tiotropium and -3.2 ± 4.64 L/min (n = 134) for salmeterol, and these were superior to placebo (-24.6 ± 4.84 L/min, n = 125, P < .05). Tiotropium was noninferior to salmeterol (estimated difference, -0.78 L/min [95% CI, -13.096 to 11.53]; P = .002; α = .025, 1-sided; noninferiority, 20 L/min). Tiotropium and salmeterol were numerically superior to placebo in some patient-reported secondary outcomes. Adverse events were comparable across treatments. Tiotropium was more effective than placebo and as effective as salmeterol in maintaining improved lung function in B16-Arg/Arg patients

  3. Nociceptive stimulation induces expression of Arc/Arg3.1 in the spinal cord with a preference for neurons containing enkephalin

    NARCIS (Netherlands)

    S.M. Hossaini (Mehdi); J.L.M. Jongen (Joost); K. Biesheuvel (Karla); D. Kuhl (Dietmar); J.C. Holstege (Jan)

    2010-01-01

    textabstractBackground: In pain processing, long term synaptic changes play an important role, especially during chronic pain. The immediate early gene Arc/Arg3.1 has been widely implicated in mediating long-term plasticity in telencephalic regions, such as the hippocampus and cortex. Accordingly, A

  4. Rapid Progression of Sporadic ALS in a Patient Carrying SOD1 p.Gly13Arg Mutation

    Science.gov (United States)

    Kim, Myung-Jin; Bae, Jae-Han; Kim, Jeong-Min; Kim, Hye Ryoun; Yoon, Byung-Nam; Sung, Jung-Joon

    2016-01-01

    Amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disease, is pathologically characterized by progressive loss of the upper and lower motor neurons. Mutations in the Cu/Zn superoxide dismutase gene (SOD1) account for about 20% of familial ALS cases and a small percentage of sporadic ALS (SALS) cases, and have revealed a validated genotype-phenotype correlation. Herein, we report a p.Gly13Arg mutation in SOD1 exon 1 in a patient with SALS who presented with a rapidly progressive course, predominantly affecting the lower motor neurons. A 48-year-old man presented with progressive weakness and muscle atrophy of the left upper and lower limbs, followed by muscle fasciculation and cramping. The clinical features of the patient were clearly suggestive of ALS, and implied a sporadic form with rapid progression, predominantly affecting the lower motor neurons. Sequencing of the SOD1 gene by PCR revealed a missense mutation of G to C (c.37G>C) in exon 1, and amino acid substitution of glycine by arginine (p.Gly13Arg). This is the first case identifying the p.Gly13Arg mutation of SOD1 in the Korean population, and clinical assessments of this patient revealed a different phenotype compared with other cases. PMID:28035186

  5. Use of Radioiodinated Peptide Arg-Arg-Leu Targeted to Neovascularization as well as Tumor Cells in Molecular Tumor Imaging

    Institute of Scientific and Technical Information of China (English)

    Xia Lu; Ping Yan; Rong-fu Wang; Meng Liu; Ming-ming Yu; Chun-li Zhang

    2012-01-01

    Objective:To explore a tumor peptide imaging agent Arginine-Arginine-Leucine (Tyr-Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys,tripeptide RRL [tRRL]) that targeted to tumor cells and tumor-derived endothelial cells (TDECs) and primarily investigate the possible relationship between tRRL and vascular endothelial growth factor receptor 2 (VEGFR-2).Methods:The tRRL sequence motif was identified as a tumor molecular marker specifically binding to TDECs.Tyrosine was conjugated to the amino terminal of RRL (Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys) for labeling with radionuclide iodine-131 (131I-tRRL).The uptake ability and molecular binding of tRRL to tumor cells and angiogenic endothelium were studied using flow cytometry and radioactivity counter in vitro.Whether VEGFR-2 is the binging site of tRRL was investigated.Biodistribution and single-photon emission computed tomography (SPECT) imaging of 131I-tRRL were used to evaluate the effectiveness of this new imaging agent to visualize varied tumor xenografts in nude mice.Results:In vitro cellular uptake experiments revealed that tRRL could not only adhere to tumor angiogenic endothelial cells but also largely accumulate in malignant tumor cells.VEGFR-2,which is highly expressed on TDECs,was probably not the solely binding ligand for tRRL targeted to tumor angiogenic endothelium.131I-tRRL mainly accumulated in tumors in vivo,not other organs at 24 h after injection.SPECT imaging with 131I-tRRL clearly visualized tumors in nude mice,especially at 24 h.Conclusion:Radioiodinated tRRL offers a noninvasive nuclear imaging method for functional molecular imaging of tumors targeted to neovascularization,and may be a promising candidate for tumor radioimmunotherapeutic carrier.

  6. Arg deficiency does not influence the course of Myelin Oligodendrocyte Glycoprotein (MOG35-55)-induced experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Jacobsen, Freja Aksel; Hulst, Camilla; Bäckström, Thomas;

    2016-01-01

    extensively studied in immune activation, roles for Arg are incompletely characterized. To investigate the role for Arg in experimental autoimmune encephalomyelitis, we studied disease development in Arg-/- mice. Methods: Arg-/- and Arg+/+ mice were generated from breeding of Arg+/- mice on the C57BL/6......Background: Inhibition of Abl kinases has an ameliorating effect on the rodent model for multiple sclerosis, experimental autoimmune encephalomyelitis, and arrests lymphocyte activation. The family of Abl kinases consists of the Abl1/Abl and Abl2/Arg tyrosine kinases. While the Abl kinase has been...... background. Mice were immunized with the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide and disease development recorded. Lymphocyte phenotypes of wild type Arg+/+ and Arg-/- mice were studied by in vitro stimulation assays and flow cytometry. Results: The breeding of Arg+/+ and Arg-/- mice showed...

  7. Selective pressure of antibiotics on ARGs and bacterial communities in manure-polluted freshwater-sediment microcosms

    Directory of Open Access Journals (Sweden)

    Wenguang eXiong

    2015-03-01

    Full Text Available The aim of this study was to investigate selective pressure of antibiotics on antibiotic resistance genes (ARGs and bacterial communities in manure-polluted aquatic environment. Three treatment groups were set up in freshwater-sediment microcosms: tetracyclines group, sulfonamides group and fluoroquinolones group. Sediment and water samples were collected on day 14 after treatment. Antibiotic concentrations, ARGs abundances and bacterial community composition were analyzed. Antibiotic concentrations were determined by ultra-performance liquid chromatography-electrospray tandem mass spectrometry. ARGs abundances were quantified by real time quantitative PCR. Bacterial community composition was analyzed based on amplicon sequencing. Of the three classes of antibiotics analyzed in the treatment groups, accumulation amounts were tetracyclines> fluoroquinolone> sulfonamides in the sediment samples, while they were sulfonamides> fluoroquinolone> tetracyclines in the water samples. In the treatment groups, the relative abundances of some tet resistance genes (tet(W and tet(X and plasmid-mediated quinolone resistance (PMQR genes (oqx(B and aac(6’-Ib in sediment samples were significantly higher than those in the paired water samples. Tetracyclines significantly selected the bacterial classes including Gammaproteobacteria, Clostridia, and the genera including Salmonella, Escherichia/Shigella, Clostridium, Stenotrophomonas in sediment samples. The significant selection on bacterial communities posed by sulfonamides and fluoroquinolones was also observed. The results indicated that sediment may supply an ideal setting for maintenance and persistence of tet resistance genes (tet(W and tet(X and PMQR genes (oqx(B and aac(6’-Ib under antibiotic pollution. The results also highlighted that antibiotics significantly selected specific bacterial communities including the taxa associated with opportunistic pathogens.

  8. Potential impact of (rs 4645878) BAX promoter -248G>A and (rs 1042522) TP53 72Arg>pro polymorphisms on epithelial ovarian cancer patients.

    Science.gov (United States)

    Dholariya, S; Mir, R; Zuberi, M; Yadav, P; Gandhi, G; Khurana, N; Saxena, A; Ray, P C

    2016-01-01

    In India, Epithelial ovarian cancer has emerged as one of the most common malignancies affecting women. Tumor protein 53 (TP53) induces expression of the B cell lymphoma 2-associated X protein (BAX) gene by directly binding to the TP53-binding element in the BAX promoter. Therefore, we hypothesized that single-nucleotide polymorphism of BAX promoter -248G>A and TP53 72Arg>Pro gene may jointly contribute to ovarian cancer risk. This study aimed at exploring the association of BAX promoter -248G>A and TP53 72Arg>Pro gene polymorphism with risk of developing EOC and its clinicopathological features and to evaluate gene-gene interaction of these two polymorphisms with risk of developing EOC. The study was conducted on 70 Epithelial ovarian cancer patients and 70 healthy controls. Genotyping of p53 codon 72 and BAX promoter gene was examined by ASO-PCR and PICA-PCR, respectively. Odds ratios and 95 % confidence intervals were calculated. We found an increased cancer risk associated with the BAX AA (ORs = 4.1, 95 %, CI = 1.23-13.97) genotype. An increased risk was also associated with the TP53 Pro/Pro (OR = 4.4, 95 % CI = 1.40-13.99) and Arg/Pro genotype (OR = 2.3, 95 % CI = 1.13-4.86). The gene-gene interaction of these polymorphisms increased EOC risk in a more than additive manner (ORs for the presence of both BAX AA and TP53 Arg/Pro genotypes = 8.7, 95 % CI = 1.66-45.48). BAX GG genotype was associated with adverse staging of cancer (P = 0.01). The findings suggest that polymorphism of BAX and TP53 genes may be potential genetic modifiers for developing ovarian cancer.

  9. P21 Ser31Arg polymorphism and cervical cancer risk: a meta-analysis.

    Science.gov (United States)

    Li, Ya; Liu, Fei; Tan, Shiqiao; Li, Shangwei

    2011-04-01

    Studies investigating the association between p21 genetic polymorphism Ser31Arg and cervical cancer (CC) risk report conflicting results. The aim of this study was to quantitatively summarize the evidence for p21 polymorphism and CC risk. Two investigators independently searched the MEDLINE, Embase, CNKI, and Chinese Biomedicine databases. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for p21 polymorphism and CC were calculated in a fixed effects model (the Mantel-Haenszel method) and a random effects model (the DerSimonian and Laird method) when appropriate. The pooled ORs were performed for codominant model (Arg/Arg vs Ser/Ser and Arg/Ser vs Ser/Ser), dominant model (Arg/Arg + Arg/Ser vs Ser/Ser), and recessive model (Arg/Arg vs Arg/Ser + Ser/Ser). Subgroup analyses were performed by country, matched controls, and Hardy-Weinberg equilibrium in the controls and study sample size. This meta-analysis included 10 case-control studies from an Asian population, which included 1415 CC cases and 1947 controls. Overall, the variant genotypes (Arg/Arg and Arg/Ser) of Ser31Arg were not associated with CC risk, when compared with the wild-type homozygote Ser/Ser (Arg/Arg vs Ser/Ser: OR, 1.30; 95% CI, 0.81-2.08; Arg/Ser vs Ser/Ser: OR, 1.06; 95% CI, 0.72-1.55). Similarly, no associations were found in the dominant and recessive models (dominant model: OR, 1.05; 95% CI, 0.73-1.51; recessive model: OR, 1.28; 95% CI, 0.86-1.90). Stratified analyses also detected no significant association in any subgroup, except among those studies from "other" country and those studies with controls deviated from Hardy-Weinberg equilibrium. No association was found between the p21 polymorphism Arg31Ser and risk of CC among Asians. In the future, additional studies based on white and African American patients should be performed to re-evaluate the association.

  10. Stationary phase expression of the arginine biosynthetic operon argCBH in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Sun Yuan

    2006-02-01

    Full Text Available Abstract Background Arginine biosynthesis in Escherichia coli is elevated in response to nutrient limitation, stress or arginine restriction. Though control of the pathway in response to arginine limitation is largely modulated by the ArgR repressor, other factors may be involved in increased stationary phase and stress expression. Results In this study, we report that expression of the argCBH operon is induced in stationary phase cultures and is reduced in strains possessing a mutation in rpoS, which encodes an alternative sigma factor. Using strains carrying defined argR, and rpoS mutations, we evaluated the relative contributions of these two regulators to the expression of argH using operon-lacZ fusions. While ArgR was the main factor responsible for modulating expression of argCBH, RpoS was also required for full expression of this biosynthetic operon at low arginine concentrations (below 60 μM L-arginine, a level at which growth of an arginine auxotroph was limited by arginine. When the argCBH operon was fully de-repressed (arginine limited, levels of expression were only one third of those observed in ΔargR mutants, indicating that the argCBH operon is partially repressed by ArgR even in the absence of arginine. In addition, argCBH expression was 30-fold higher in ΔargR mutants relative to levels found in wild type, fully-repressed strains, and this expression was independent of RpoS. Conclusion The results of this study indicate that both derepression and positive control by RpoS are required for full control of arginine biosynthesis in stationary phase cultures of E. coli.

  11. ARGE DFC - A European approach to MCFC commercialization

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, P.; Huppmann, G. [MTU Friedrichshafen GmbH, Muenchen (Germany); Heiming, A. [Ruhgras AG, Dorsten (Germany)] [and others

    1996-12-31

    The largest European program for the commercialization of the molten carbonate fuel cell technology is carried out by the European Direct Fuel Cell Consortium (ARGE DFC). The consortium consists of the following companies: (1) MTU Friedrichshafen GmbH (Germany), within the DaimlerBenz Group responsible for off-road propulsion and decentralized energy systems. (2) Haldor Topsoe A/S (Denmark), a plant engineering company and specialist for catalytic processes (3) Elkraft A.m.b.A. (Denmark), one of the countries two utility companies (4) Ruhrgas AG (Germany), the largest German gas company (5) RWE AG (Germany), the largest German electrical utility company MTU acts as a consortium leader. The company shares a license and technology exchange agreement with Energy Research Corporation of Danbury, Connecticut.

  12. A novel fibrinogen mutation (γ Thr277Arg) causes hereditary hypofibrinogenemia in a Chinese family.

    Science.gov (United States)

    Zhu, Liqing; Wang, Mingshan; Xie, Haixiao; Jin, Yanhui; Yang, Lihong; Xu, Pengfei

    2013-09-01

    Congenital hypofibrinogenemia is a rare disorder caused by heterozygous mutations in one of the three fibrinogen genes--fibrinogen α-chain (FGA), fibrinogen β-chain (FGB) and fibrinogen γ-chain (FGG)--which code for the Aα, Bβ and γ chains, respectively. In this study, we identified a genetic defect in the FGG underlying the hypofibrinogenemia. The proposita had a prolonged blood clotting time (thrombin time 24.5 s, prothrombin time 16.8 s) and a low level of plasma fibrinogen (0.71 g/l by Clauss method and 0.79 g/l by immunoturbidimetry). DNA screening of the whole fibrinogen gene revealed a heterozygous GC mutation at nucleotide 7482 in her FGG gene. Her father and her half-brother are also heterozygous for this mutation. This mutation contributes to Thr277 → Arg in the γ chain of fibrinogen. To the best of our knowledge, this is the first report of such a mutation that is associated with hypofibrinogenemia.

  13. TP53 Arg72Pro polymorphism is associated with esophageal cancer risk: A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    De-Ke Jiang; Lei Yao; Wen-Zhang Wang; Bo Peng; Wei-Hua Ren; Xian-Mei Yang; Long Yu

    2011-01-01

    AIM: To investigate the association between TP53 Ar-g72Pro polymorphism and esophageal cancer (EC) risk using meta-analysis.METHODS: All eligible studies published before March 1, 2010 were selected by searching PubMed using key-words “p53” or “TP53”, “polymorphism” or “variation”, “esophageal” and “cancer” or “carcinoma”. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were assessed for EC risk associated with TP53 Arg72Pro polymorphism using fixed- and random-effects models.RESULTS: Nine case-control studies involving 5545 subjects were included in this meta-analysis. Signifi-cantly reduced risk of EC was associated with TP53 genotypes for Arg/Arg + Arg/Pro vs Pro/Pro (OR = 0.73, 95% CI: 0.57-0.94, P = 0.014). Subgroup analy-ses according to the source of controls and the speci-mens used for determining TP53 Arg72Pro genotypes or sample size showed that significantly reduced risk was observed only in studies which have population-based controls (Arg/Arg vs Pro/Pro: OR = 0.56, 95% CI: 0.47-0.66, P < 0.001), and use white blood cells or normal tissue to assess TP53 genotypes of cases (Arg/Arg vs Pro/Pro: OR = 0.56, 95% CI: 0.47-0.65, P < 0.001) or include at least 200 subjects (Arg/Arg vs Pro/Pro: OR = 0.56, 95% CI: 0.47-0.65, P < 0.001). Analysis restricted to well-designed studies also sup-ported the significantly decreased risk of EC (Arg/Arg vs Pro/Pro: OR = 0.54, 95% CI: 0.46-0.64, P < 0.001). CONCLUSION: TP53 Arg72 carriers are significantly as-sociated with decreased EC risk. Nevertheless, more well-designed studies are needed to confirm our findings.

  14. The XRCC1 Arg194Trp polymorphism is significantly associated with lung adenocarcinoma: a case-control study in an Eastern European Caucasian group

    Directory of Open Access Journals (Sweden)

    Cătană A

    2015-11-01

    Full Text Available Andreea Cătană,1 Monica Pop,2 Bianca Domokos Hincu,2 Ioan V Pop,1 Felicia M Petrişor,1 Mihai D Porojan,3 Radu A Popp1 1Department of Molecular Sciences, 2Department of Pneumology, 3Department of Internal Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania Abstract: DNA repair plays an important role in maintaining the integrity of the genome by repairing DNA damage induced by carcinogens. Certain genetic polymorphisms that occur in DNA-repair genes may affect the ability to repair DNA defects, and may represent a risk factor in carcinogenesis. The gene XRCC1 is involved in DNA repair. The purpose of our study was to investigate the association between XRCC1 Arg194Trp and Arg399Gln polymorphisms and the risk of lung cancer in a Romanian population. We recruited 222 healthy controls and 102 patients with lung cancer. Genotypes were determined by multiplex polymerase chain-reaction restriction fragment-length polymorphism. Statistical analysis (odds ratio, recessive model revealed an increased risk for lung cancer for the homozygous 194Trp genotype (χ2=0.186, odds ratio 10.667, 95% confidence interval 1.309–86.933; P=0.007. Also, we found an association between the 194Trp allele and women with lung adenocarcinoma. In conclusion, the results of the study place the XRCC1 Arg194Trp polymorphism among independent risk factors for developing lung cancer. Keywords: lung cancer, XRCC1 Arg194Trp, XRCC1 Arg399Gln

  15. Clon and Sequence Analysis of Mitochondrial ND3,ND4L and tRNA-Arg Gene for Sichuan Black Bear (Ursus thibetnnus mupinensis)%四川黑熊ND3、ND4L和tRNA-Arg基因的克隆和序列分析

    Institute of Scientific and Technical Information of China (English)

    陈瑜; 吴夏; 彭正松; 周材权; 侯万儒

    2007-01-01

    克隆并测定了四川黑熊(Ursus thibetanus mupinensis)线粒体基因组764 bp的片段,根据序列同源性比较,该DNA片段包括2个蛋白质编码基因:ND3和ND4L基因,以及1个tRNA-Arg基因.四川黑熊的ND3基因和ND4L基因的DNA序列和所编码的氨基酸序列与马来熊、棕熊、美洲黑熊和北极熊的同源性分别为:90%和95%、93%和97%、91%和96%、93%和97%;89%和98.98%、88%和98.98%、89%和100%、89%和98.98%.与棕熊、美洲黑熊和北极熊tRNA-Arg(CGA)的同源性分别为95.65%、94.20%和94.20%.拓扑结构比较显示,四川黑熊的ND3基因所编码的氨基酸序列比美洲黑熊的少了1个蛋白激酶C磷酸化位点.

  16. Meta-analysis on the relationship between leptin receptor Gln223Arg and Prol019Pro gene polymorphism and obesity in the Chinese population%中国人群瘦素受体Gln223Arg、Pr01019Pro基因多态性与肥胖关联性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    阳赣萍; 彭司华; 左双燕; 王一任; 彭小宁; 曾小敏

    2011-01-01

    目的 探讨瘦素受体(LEPR) Gln223Arg、Prol019Pro基因多态性与肥胖的关联性.方法 计算机检索万方、CNKI、维普、CBM、PubMed、EMBASE数据库,收集1979-2010年公开发表的关于中国人群LEPR Gln223Arg、LEPR Pro1 019Pro基因多态性与肥胖的病例对照研究的文献,选择OR值及其95%CI作为Meta分析指标.利用Stata 10.0软件对各研究结果进行异质性检验和效应值合并计算.结果 根据统一的纳入和剔除标准,纳入15篇文献,其中LEPRGln223Arg基因多态性相关文献9篇,共有肥胖者1096例,对照组949人;LEPR Prol019Pro基因多态性相关文献8篇,共有肥胖者961例,对照组818人.LEPR Gln223Arg基因多态性与肥胖关联性的研究中,LEPR-668位点基因G/A的OR=0.66(95%CI:0.49~0.89),将有A→3基因突变的AG基因型和GG基因型合并后与AA基因型比较,肥胖易感性降低(OR=0.50,95%CI:0.32~0.77)有统计学意义;在LEPR Prol019Pro基因多态性与肥胖关联性的研究中,LEPR-3057位点基因A/G的OR=1,61 (95%CI:1.15~2.26),有G→A基因突变的基因型AG和基因型AA合并后与GG基因型比较,肥胖易感性升高(OR=1.50,95%CI:1.08~2.08),有统计学意义.结论 中国汉族为主的人群LEPR Gln223Arg和LEPR Prol019Pro基因多态性与肥胖的发生均有关联.%Objective To evaluate the associations between polymorphisms of LEPR Gln223Arg,LEPR Pro 1019Pro and the risk on obesity.Methods A computerized search on literature was carried out in Wanfang,CNKI,VIP databases and CBM,PubMed,EMBASE databases to collect articles published between 1979 and 2010 concerning the associations between polymorphisms of LEPR Gln223Arg and/or LEPR Pro 1019Pro and risk of obesity in the Chinese population.Odds ratios (ORs) were used to assess the strength of the association,and 95% confidence intervals (CIs) to present the precision of the estimates.Meta-analysis was performed using the STATA statistical software.Results Fifteen literature

  17. XRCC1 Arg399Gln polymorphism confers risk of breast cancer in American population: a meta-analysis of 10846 cases and 11723 controls.

    Directory of Open Access Journals (Sweden)

    Tao Bu

    Full Text Available BACKGROUND: In the X-ray repair cross-complementing group 1 (XRCC1 gene, a polymorphism, Arg399Gln (rs25487, has been shown to change neoconservative amino acid and thus result in alternation of DNA repair capacity. Numerous studies have investigated the association between Arg399Gln and breast cancer risk in the American population, but yielding inconsistent results. This study aimed to clarify the role of this polymorphism in susceptibility to breast cancer. METHODS: Literatures were searched in multiple databases including PubMed, Springer Link, Ovid, EBSCO and ScienceDirect databases up to April 2013. A comprehensive meta-analysis was conducted to estimate the overall odds ratio (OR, by integrating data from 18 case control studies of 10846 cases and 11723 controls in the American population. RESULTS: Overall, significant association was observed between the Arg399Gln polymorphism and breast cancer risk under the random-effects model (OR for dominant model = 1.12, 95% CI: 1.02-1.24, P heterogeneity = 0.003; OR for additive model = 1.07, 95% CI: 1.01-1.14, P heterogeneity = 0.017. Further sensitivity analysis supported the robust stability of this current result by showing similar ORs before and after removal of a single study. CONCLUSIONS: This meta-analysis suggests that the XRCC1 Arg399Gln polymorphism may significantly contribute to susceptibility of breast cancer in the American population.

  18. XRCC1 Arg399Gln Polymorphism Confers Risk of Breast Cancer in American Population: A Meta-Analysis of 10846 Cases and 11723 Controls

    Science.gov (United States)

    Sun, Yong; Zhao, Li; Peng, Yang; Zhou, Shudong; Li, Lixia; Chen, Sidong; Gao, Yanhui

    2014-01-01

    Background In the X-ray repair cross-complementing group 1 (XRCC1) gene, a polymorphism, Arg399Gln (rs25487), has been shown to change neoconservative amino acid and thus result in alternation of DNA repair capacity. Numerous studies have investigated the association between Arg399Gln and breast cancer risk in the American population, but yielding inconsistent results. This study aimed to clarify the role of this polymorphism in susceptibility to breast cancer. Methods Literatures were searched in multiple databases including PubMed, Springer Link, Ovid, EBSCO and ScienceDirect databases up to April 2013. A comprehensive meta-analysis was conducted to estimate the overall odds ratio (OR), by integrating data from 18 case control studies of 10846 cases and 11723 controls in the American population. Results Overall, significant association was observed between the Arg399Gln polymorphism and breast cancer risk under the random-effects model (OR for dominant model = 1.12, 95% CI: 1.02–1.24, Pheterogeneity = 0.003; OR for additive model = 1.07, 95% CI: 1.01–1.14, Pheterogeneity = 0.017). Further sensitivity analysis supported the robust stability of this current result by showing similar ORs before and after removal of a single study. Conclusions This meta-analysis suggests that the XRCC1 Arg399Gln polymorphism may significantly contribute to susceptibility of breast cancer in the American population. PMID:24489692

  19. Aminopeptidase activity in rat brain synaptosomes - 2-mercaptoethanol stimulation and Arg-vasopressin degradation

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, W.H.; Orawski, A.T.

    1986-03-05

    Rat brain synaptic plasma membranes contain an amastatin-inhibited aminopeptidase activity which degrades Arg-vaso-pressin (AVP). The pH optimum for AVP cleavage was found to be 6.8, similar to that reported for oxytocin. The ability of other peptides and arylamides such as oxytocin, Tyr-Phe-Met-Arg-Phe-NH/sub 2/ and Arg-Arg-..beta..NA to inhibit cleavage of (/sup 3/H-Tyr/sup 2/)-AVP suggests that the enzyme may not be specific for AVP. The AVP-cleaving activity has been solubilized and partially characterized. Synaptosomes were lysed with hypotonic buffer, washed, and extracted with 1% Nonidet P-40 detergent. The solubilized protein was chromatographed by gel filtration HPLC on Superose 6. A single peak of activity was found with a M.W. = 117,000 which could hydrolyze 1mM Ala-..beta..NA, Arg-..beta..NA, Arg-Arg-..beta..NA, Phe-Met and Phe-Arg as well as slowly cleave AVP with the ultimate release of /sup 3/H-Tyr. 2-Mercaptoethanol (3.9mM) (ME) stimulated activity 3.6 to 6.6-fold for arylamide and dipeptide substrates, but 35-fold for labelled AVP, possibly owing to reduction of the AVP disulfide bond. All activities in the presence of ME were completely inhibited by 0.2mM amastatin.

  20. Transcriptome analysis of the Lactococcus lactis ArgR and AhrC regulons

    DEFF Research Database (Denmark)

    Larsen, Rasmus; van Hijum, Sacha A. F. T.; Martinussen, Jan;

    2008-01-01

    In previous studies, we have shown that direct protein-protein. interaction between the two regulators ArgR and AhrC in Lactococcus lactis is required for arginine-dependent repression of the biosynthetic argC promoter and the activation of the catabolic arcA promoter. Here, we establish the global...

  1. Change in microbial community in landfill refuse contaminated with antibiotics facilitates denitrification more than the increase in ARG over long-term

    Science.gov (United States)

    Wu, Dong; Chen, Guanzhou; Zhang, Xiaojun; Yang, Kai; Xie, Bing

    2017-01-01

    In this study, the addition of sulfamethazine (SMT) to landfill refuse decreased nitrogen intermediates (e.g. N2O and NO) and dinitrogen (N2) gas fluxes to 5%) for the dominant bacterial hosts (Rhodothermus, ~20%) harboring nosZ and norB genes that significantly correlated with nitrogen emission pattern, while sulfamethazine amendment completely reduced the relative abundance of the “original inhabitants” functioning to produce NOx gas reduction. The main ARG carriers (Pseudomonas) that were substantially enriched in the SMT group had lower levels of denitrifying functional genes, which could imply that denitrification is influenced more by bacterial dynamics than by abundance of ARGs under antibiotic pressures. PMID:28120869

  2. Dissemination of antibiotic resistance genes from antibiotic producers to pathogens

    DEFF Research Database (Denmark)

    Jiang, Xinglin; Ellabaan, Mostafa M Hashim; Charusanti, Pep

    2017-01-01

    It has been hypothesized that some antibiotic resistance genes (ARGs) found in pathogenic bacteria derive from antibiotic-producing actinobacteria. Here we provide bioinformatic and experimental evidence supporting this hypothesis. We identify genes in proteobacteria, including some pathogens......, that appear to be closely related to actinobacterial ARGs known to confer resistance against clinically important antibiotics. Furthermore, we identify two potential examples of recent horizontal transfer of actinobacterial ARGs to proteobacterial pathogens. Based on this bioinformatic evidence, we propose...... results support the existence of ancient and, possibly, recent transfers of ARGs from antibiotic-producing actinobacteria to proteobacteria, and provide evidence for a defined mechanism....

  3. Mallotus philippinensis Muell. Arg (Euphorbiaceae: Ethnopharmacology and Phytochemistry Review

    Directory of Open Access Journals (Sweden)

    Mayank Gangwar

    2014-01-01

    Full Text Available Mallotus philippinensis Muell. Arg (Euphorbiaceae are widely distributed perennial shrub or small tree in tropical and subtropical region in outer Himalayas regions with an altitude below 1,000 m and are reported to have wide range of pharmacological activities. Mallotus philippinensis species are known to contain different natural compounds, mainly phenols, diterpenoids, steroids, flavonoids, cardenolides, triterpenoids, coumarins, isocoumarins, and many more especially phenols; that is, bergenin, mallotophilippinens, rottlerin, and isorottlerin have been isolated, identified, and reported interesting biological activities such as antimicrobial, antioxidant, antiviral, cytotoxicity, antioxidant, anti-inflammatory, immunoregulatory activity protein inhibition against cancer cell. We have selected all the pharmacological aspects and toxicological and all its biological related studies. The present review reveals that Mallotus philippinensis is a valuable source of medicinally important natural molecules and provides convincing support for its future use in modern medicine. However, the existing knowledge is very limited about Mallotus philippinensis and its different parts like steam, leaf, and fruit. Further, more detailed safety data pertaining to the acute and subacute toxicity and cardio- and immunotoxicity also needs to be generated for crude extracts or its pure isolated compounds. This review underlines the interest to continue the study of this genus of the Euphorbiaceae.

  4. Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

    Energy Technology Data Exchange (ETDEWEB)

    Olinto, S.C.F. [Faculdade de Ciências Integradas do Pontal, Universidade Federal de Uberlândia, Ituiutaba, MG (Brazil); Adrião, M.G. [Departamento de Morfologia e Fisiologia, Universidade Federal Rural de Pernambuco, Recife, PE (Brazil); Castro-Barbosa, T.; Goulart-Silva, F.; Nunes, M.T. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2012-06-01

    The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (∼250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (an NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

  5. Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

    Directory of Open Access Journals (Sweden)

    S.C.F. Olinto

    2012-11-01

    Full Text Available The amino acid arginine (Arg is a recognized secretagogue of growth hormone (GH, and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO, which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (~250 g were removed, divided into two halves, pooled (three hemi-pituitaries and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM, the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM and a cyclic guanosine monophosphate (cGMP analogue (8-Br-cGMP, 1 mM increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM blunted the effect of SNP, and the combined treatment with Arg and L-NAME (a NO synthase (NOS inhibitor, 55 mM abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

  6. Influence of Glu/Arg, Asp/Arg, and Glu/Lys Salt Bridges on α-Helical Stability and Folding Kinetics.

    Science.gov (United States)

    Meuzelaar, Heleen; Vreede, Jocelyne; Woutersen, Sander

    2016-06-07

    Using a combination of ultraviolet circular dichroism, temperature-jump transient-infrared spectroscopy, and molecular dynamics simulations, we investigate the effect of salt bridges between different types of charged amino-acid residue pairs on α-helix folding. We determine the stability and the folding and unfolding rates of 12 alanine-based α-helical peptides, each of which has a nearly identical composition containing three pairs of positively and negatively charged residues (either Glu(-)/Arg(+), Asp(-)/Arg(+), or Glu(-)/Lys(+)). Within each set of peptides, the distance and order of the oppositely charged residues in the peptide sequence differ, such that they have different capabilities of forming salt bridges. Our results indicate that stabilizing salt bridges (in which the interacting residues are spaced and ordered such that they favor helix formation) speed up α-helix formation by up to 50% and slow down the unfolding of the α-helix, whereas salt bridges with an unfavorable geometry have the opposite effect. Comparing the peptides with different types of charge pairs, we observe that salt bridges between side chains of Glu(-) and Arg(+) are most favorable for the speed of folding, probably because of the larger conformational space of the salt-bridging Glu(-)/Arg(+) rotamer pairs compared to Asp(-)/Arg(+) and Glu(-)/Lys(+). We speculate that the observed impact of salt bridges on the folding kinetics might explain why some proteins contain salt bridges that do not stabilize the final, folded conformation.

  7. The Escherichia coli argW-dsdCXA genetic island is highly variable, and E. coli K1 strains commonly possess two copies of dsdCXA.

    Science.gov (United States)

    Moritz, Rebecca L; Welch, Rodney A

    2006-11-01

    The genome sequences of Escherichia coli pathotypes reveal extensive genetic variability in the argW-dsdCXA island. Interestingly, the archetype E. coli K1 neonatal meningitis strain, strain RS218, has two copies of the dsdCXA genes for d-serine utilization at the argW and leuX islands. Because the human brain contains d-serine, an epidemiological study emphasizing K1 isolates surveyed the dsdCXA copy number and function. Forty of 41 (97.5%) independent E. coli K1 isolates could utilize d-serine. Southern blot hybridization revealed physical variability within the argW-dsdC region, even among 22 E. coli O18:K1:H7 isolates. In addition, 30 of 41 K1 strains, including 21 of 22 O18:K1:H7 isolates, had two dsdCXA loci. Mutational analysis indicated that each of the dsdA genes is functional in a rifampin-resistant mutant of RS218, mutant E44. The high percentage of K1 strains that can use d-serine is in striking contrast to our previous observation that only 4 of 74 (5%) isolates in the diarrheagenic E. coli (DEC) collection have this activity. The genome sequence of diarrheagenic E. coli isolates indicates that the csrRAKB genes for sucrose utilization are often substituted for dsdC and a portion of dsdX present at the argW-dsdCXA island of extraintestinal isolates. Among DEC isolates there is a reciprocal pattern of sucrose fermentation versus d-serine utilization. The ability to use d-serine is a trait strongly selected for among E. coli K1 strains, which have the ability to infect a wide range of extraintestinal sites. Conversely, diarrheagenic E. coli pathotypes appear to have substituted sucrose for d-serine as a potential nutrient.

  8. WOOD ANATOMY OF Phyllanthus sellowianus Müll. Arg. (PHYLLANTHACEAE

    Directory of Open Access Journals (Sweden)

    Luciano Denardi

    2013-06-01

    Full Text Available http://dx.doi.org/10.5902/198050989294The present study aimed to describe the wood anatomy of Phyllanthus sellowianus Müll. Arg.(Phyllanthaceae, as well as the research of anatomical characters associated with the flexibility of their stems, desirable characteristic for bioengineering works. Belonging to the group of  reophyllous and with up to three  meters in height, the species occurs naturally in the south of Brazil, Uruguay and Argentina. The exsicat and wood sample from a P. sellowianus, located in the municipality of Santa Maria, Rio Grande do Sul state, Brazi, were deposited in the University Federal de Santa Maria under the numbers HDCF 5587 e 5588. Standard technique was used to set the histological lamina of wood. For macerations used the method of Jeffrey. The Wood anatomy description followed the IAWA Committee (1989. The microscopic analysis revealed the presence vassels of small diameter (< 60µm, radial multiples of 2 to 4 units, and simple perforation plates, obliquely, axial parenchyma absent, heterogeneous rays, with 1-3 cells large, and gelatinous fibers. The absence of axial parenchyma and laticifer tubes is compatible to the Phyllanthaceae group. The presence of perforated ray cells is, probably, the main anatomic component for differentiation of P. sellowianus from the other species of the genera. The abundant presence of gelatinous fibers certainly is one of the main anatomical characteristics related to the high flexibility of its stem.

  9. A new factor X defect (factor X Padua 3): a compound heterozygous between true deficiency (Gly(380)-->Arg) and an abnormality (Ser(334)-->Pro).

    Science.gov (United States)

    Vianello, F; Lombardi, A M; Boldrin, C; Luni, S; Girolami, A

    2001-11-15

    We report a novel mutation in Factor X (FX) gene which results in a phenotype without any bleeding tendency. The proband has been found to be a compound heterozygote between a novel FX true deficiency (Gly(380)-->Arg) and a previously reported dysfunctional mutation Ser(334)-->Pro (FX Marsiglia). Prothrombin time (PT) and partial thromboplastin time (PTT) were moderately prolonged and were fully corrected by the addition of normal serum. Her FX activity level varied between 8% and 19% of normal according to the method used whereas the FX antigen level was 40% of the normal control value. All the exons and intron/exon junctions of the FX gene were studied using a combined approach of polymerase chain reaction and conformation sensitive gel electrophoresis. A transversion G to A in exon 8 resulting in the replacement of Gly380 by Arg was found in the proband, in the father and in a proband's brother, whereas heterozygous FX Marsiglia was present in the proband's mother and her sister. Gly380 is strictly linked to Ser379, a component of the catalytic triad. The substitution of Gly for Arg causes the introduction of a large charged amino acid which could affect the catalytic function of FX leading to secretion problem, accounting for the cross-reactive material (CRM) negative phenotype.

  10. Seasonal variations in antibiotic resistance gene transport in the almendares river, havana, cuba.

    Science.gov (United States)

    Knapp, Charles W; Lima, Lazaro; Olivares-Rieumont, Susana; Bowen, Emma; Werner, David; Graham, David W

    2012-01-01

    Numerous studies have quantified antibiotic resistance genes (ARG) in rivers and streams around the world, and significant relationships have been shown that relate different pollutant outputs and increased local ARG levels. However, most studies have not considered ambient flow conditions, which can vary dramatically especially in tropical countries. Here, ARG were quantified in water column and sediment samples during the dry- and wet-seasons to assess how seasonal and other factors influence ARG transport down the Almendares River (Havana, Cuba). Eight locations were sampled and stream flow estimated during both seasons; qPCR was used to quantify four tetracycline, two erythromycin, and three beta-lactam resistance genes. ARG concentrations were higher in wet-season versus dry-season samples, which combined with higher flows, indicated much greater ARG transport downstream during the wet-season. However, water column ARG levels were more spatially variable in the dry-season than the wet-season, with the proximity of waste outfalls strongly influencing local ARG levels. Results confirm that dry-season sampling provides a useful picture of the impact of individual waste inputs on local stream ARG levels, whereas the majority of ARGs in this tropical river were transported downstream during the wet-season, possibly due to re-entrainment of ARG from sediments.

  11. Seasonal variations in antibiotic resistance gene transport in the Almendares River, Havana, Cuba

    Directory of Open Access Journals (Sweden)

    Charles W Knapp

    2012-11-01

    Full Text Available Numerous studies have quantified antibiotic resistance genes (ARG in rivers and streams around the world, and significant relationships have been shown that relate different pollutant outputs and increased local ARG levels. However, most studies have not considered ambient flow conditions, which can vary dramatically especially in tropical countries. Here, ARG were quantified in water-column and sediment samples during the dry-and wet-seasons to assess how seasonal and other factors influence ARG transport down the Almendares River (Havana, Cuba. Eight locations were sampled and stream flow estimated during both seasons; qPCR was used to quantify four tetracycline, two erythromycin, and three beta-lactam resistance genes. ARG concentrations were higher in wet-season versus dry-season samples, which combined with higher flows, indicated greater ARG transport downstream during the wet season. Water-column ARG levels were more spatially variable in the dry-season than the wet-season, with the proximity of waste outfalls strongly influencing local ARG levels. Results confirm that dry-season sampling provides a useful picture of the impact of individual waste inputs on local stream ARG levels, whereas, the majority of ARGs in this tropical river were transported downstream during the wet season, possibly due to re-entrainment of ARG from sediments.

  12. Association between p21 Ser31Arg polymorphism and cancer risk: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Hongxia Ma; Ziyuan Zhou; Sheng Wei; Qingyi Wei

    2011-01-01

    P21 (CDKN1A), a key cell cycle regulatory protein that governs cell cycle progression from G1 to S phase, can regulate cell proliferation, growth arrest, and apoptosis. The Ser31Arg polymorphism is located in the highly conserved region of p21 and may encode functionally distinct proteins. Although many epidemiological studies have been conducted to evaluate the association between the p21 Ser31Arg polymorphism and cancer risk, the findings remain conflicting. This meta-analysis with 33 077 cases and 45 013 controls from 44 published case-control studies showed that the variant homozygous 31Arg/Arg genotype was associated with an increased risk of numerous types of cancers in a random-effect model (homozygote comparison: OR = 1.17, 95% CI = 0.99 to 1.37, P = 0.0002 for the heterogeneity test; recessive model comparison: OR = 1.16, 95% CI = 1.01 to 1.33, P = 0.0001 for the heterogeneity test). Stratified analysis revealed that increased cancer risk associated with the 31Arg/Arg genotype remained significant in subgroups of colorectal cancer, estrogen-related cancer, Caucasians, population-based studies, studies with matching information or a larger sample size. Heterogeneity analysis showed that tumor type contributed to substantial between-study heterogeneity (recessive model comparison: x2 = 21.83, df = 7, P = 0.003). The results from this large-sample sized meta-analysis suggest that the p21 31Arg/Arg genotype may serve as a potential marker for increased cancer risk.

  13. Polimorfisme Gly972Arg Gen IRS-1 dan Cys981Tyr Gen PTPN1 sebagai Faktor Risiko pada Sindrom Metabolik dengan Riwayat Berat Bayi Lahir Rendah

    Directory of Open Access Journals (Sweden)

    Hikmat Permana

    2012-09-01

    Full Text Available Increasing prevalence of obesity occurs worldwide and can affect all ages levels. Risk factors of increasing metabolic syndrome were associated with changes in lifestyle, obesity and low birth weight (LBW. This study was aimed to analyze the genotype IRS-1, genotype PTPN1 and LBW in metabolic syndrome risk factors. In 2009, this restrospective cohort study was comprised of 97 LBW and 100 normal birth weight (NBW, aged 20–21 years old, from the previous cohort study in District Tanjung Sari since 1989. The role of IRS-1 gene, PTPN1 gene and LBW in the metabolic syndrome factors were analyzed using multiple logistic regressions. The result showed there were no significant relationship between IRS-1 and PTPN1 genotype with metabolic syndrome factors but only IRS-1 genotype was significantly associated with trygliceride (p=0.006. Gly972Arg IRS-1 gene polymorphism in LBW has predictive value of increasing diastolic blood pressure, waist circumference and trygliceride. Cys981 Tyr PTPN1 gene polymorphism showed a risk factor for systolic blood pressure and high density lipoprotein (HDL cholesterol. Gly972Arg IRS-1 gene polymorphism was a dominant factor to increase diastolic blood pressure, waist circumference and trygliceride. In conclusions, Cys981 Tyr PTPN1 gene polymorphism is a risk factor of increased systolic blood pressure and HDL cholesterol, and LBW is the risk factor increasing fasting glucose level.

  14. Meta and pooled analyses of FGFR4 Gly388Arg polymorphism as a cancer prognostic factor.

    Science.gov (United States)

    Frullanti, Elisa; Berking, Carola; Harbeck, Nadia; Jézéquel, Pascal; Haugen, Aage; Mawrin, Christian; Parise, Orlando; Sasaki, Hidefumi; Tsuchiya, Norihiko; Dragani, Tommaso A

    2011-07-01

    Fibroblast growth factor receptor 4 (FGFR4) contains a Gly388Arg functional polymorphism (rs351855) that has shown contrasting results in association studies. In this study, we assessed the association between the FGFR4 Gly388Arg polymorphism and cancer prognosis. Meta-analysis and pooled analysis of 6817 and 2537 cancer cases, respectively, were carried out by nodal status and overall survival. The study included the following types of cancer: brain, breast, colorectal, head and neck, larynx, lung, melanoma, prostate, sarcomas. A statistically significant association between the Arg388Arg genotype and nodal involvement was found in the meta-analysis (odds ratio=1.33, 95% confidence interval 1.01-1.74). In the pooled analysis, the Arg388 allele carriers showed an increased hazard of poor overall survival compared with homozygous carriers of the common Gly388 allele, even after adjusting for nodal status (hazard ratio=1.21, 95% confidence interval 1.05-1.40). These results provide evidence of a role for the FGFR4 Gly388Arg polymorphism in modulating patients' outcome in different types of cancer, thus offering to clinicians a new marker to predict predisposition to poor survival in cancer patients.

  15. Apert Syndrome: Molecularly Confirmed C.758C>G (P.Pro253Arg) in FGFR2

    Energy Technology Data Exchange (ETDEWEB)

    Cha Gon, Lee, E-mail: leechagon@eulji.ac.kr [Department of Pediatrics, Eulji General Hospital, College of Medicine, Eulji University, 68 Hangeulbiseok-ro, Nowon-gu, Seoul 139-711 (Korea, Republic of)

    2016-03-21

    A 5-day-old girl was referred to our clinic for evaluation of congenital malformations. She was identified with a pathogenic mutation c.758C>G (p.Pro253Arg) in FGFR2 gene using targeted exome sequencing. The de novo mutation was confirmed with Sanger sequencing in the patient and her parents. She showed occipital plagiocephaly with frontal bossing (Figure A and B). Skull frontal and lateral radiography revealed fusion of most of the sutures except coronal suture, with convolutional markings (Figure D and E). She had complete cleft palate (Figure C). Her fused bilateral hands showed type II syndactyly with complete syndactyly between the ring and the little fingers (Figure F1-F3). Both toes were simple syndactyly with side-to-side fusion of skin (Figure G1-)

  16. Evaluating antibiotic resistance genes in soils with applied manures

    Science.gov (United States)

    Antibiotics are commonly used in livestock production to promote growth and combat disease. Recent studies have shown the potential for spread of antibiotic resistance genes (ARG) to the environment following application of livestock manures. In this study, concentrations of bacteria with ARG in soi...

  17. The association between the TP53 Arg72Pro polymorphism and colorectal cancer: An updated meta-analysis based on 32 studies

    Science.gov (United States)

    Tian, Xin; Dai, Shundong; Sun, Jing; Jiang, Shenyi; Jiang, Youhong

    2017-01-01

    Several previous studies evaluated the association between the Arg72Pro (rs1042522) polymorphism in the TP53 tumor suppressor gene and colorectal cancer (CRC). However, the results are conflicting. This meta-analysis aimed to shed new light on the precise association between TP53 variants and CRC. We analyzed 32 published case-control studies involving 8,586 cases and 10,275 controls using crude odd ratios (ORs) with 95% confidence intervals (CIs). The meta-analysis was performed using a fixed-effect or random-effects model, as appropriate. We found that the TP53 Arg72Pro polymorphism was not significantly associated with CRC risk in the overall population. However, subgroup analysis based on ethnicity revealed an increased risk of CRC among Asians (CC vs. GC+GG: OR=1.22, 95% CI: 1.02-1.45), and similar results were found for rectal cancer (CC vs. GC+GG: OR=1.34, 95% CI: 1.120-1.62). These results suggest that the TP53 Arg72Pro polymorphism CC genotype may contribute to an increased risk of CRC, especially for rectal cancer and among Asians. PMID:27901479

  18. FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung.

    Science.gov (United States)

    Falvella, Felicia S; Frullanti, Elisa; Galvan, Antonella; Spinola, Monica; Noci, Sara; De Cecco, Loris; Nosotti, Mario; Santambrogio, Luigi; Incarbone, Matteo; Alloisio, Marco; Calabrò, Elisa; Pastorino, Ugo; Skaug, Vidar; Haugen, Aage; Taioli, Emanuela; Dragani, Tommaso A

    2009-06-15

    The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1-1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3-2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue.

  19. Associations between Dietary Patterns, ADRβ2 Gln27Glu and ADRβ3 Trp64Arg with Regard to Serum Triglyceride Levels: J-MICC Study

    Directory of Open Access Journals (Sweden)

    Hinako Nanri

    2016-09-01

    Full Text Available Interactions between dietary patterns and 2 β-adrenergic receptor (ADRβ gene polymorphisms (ADRβ2 Gln27Glu and ADRβ3 Trp64Arg were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35–69 years enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRβ3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01 were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01. However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55. Interactions between other dietary patterns and ADRβ polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRβ3 polymorphism modifies the effects of the bread pattern on triglyceride levels.

  20. Site-directed mutagenesis from Arg195 to His of a microalgal chloroplastidial glycerol-3-phosphate acyltransferase causes an increase in phospholipid levels in yeast

    Directory of Open Access Journals (Sweden)

    Long-Ling eOuyang

    2016-03-01

    Full Text Available To analyze the contribution of glycerol-3-phosphate acyltransferase (GPAT to the first acylation of glycerol-3-phosphate (G-3-P, the present study focused on a functional analysis of the GPAT gene from Lobosphaera incisa (designated as LiGPAT and the subcellular localization of the encoded protein LiGPAT. A full-length cDNA of LiGPAT consisting of a 1,305-bp ORF, a 1,652-bp 5′-UTR, and a 354-bp 3′-UTR, was cloned. The ORF encoded a 434-amino acid peptide, of which 63 residues at the N-terminus defined a chloroplast transit peptide. LiGPAT was exclusively localized to chloroplasts, which was shown by co-expression of LiGPAT with eGFP in Chlamydomonas reinhardtii and by immunogold labeling in L. incisa. Considering the conservation of His among the G-3-P binding sites from chloroplastidial GPATs and the substitution of His by Arg at position 195 in the LiGPAT mature protein (designated mLiGPAT, we established the heterologous expression of either mLiGPAT or its mutant (Arg195His (sdmLiGPAT in the GPAT-deficient yeast mutant gat1Δ. Lipid profile analyses of these transgenic yeasts not only validated the acylation function of LiGPAT but also indicated that the site-directed mutagenesis from Arg195 to His led to an increase in the phospholipid level in yeast. Semi-quantitative analysis of mLiGPAT and sdmLiGPAT, together with the structural superimposition of their G-3-P binding sites, indicated that the increased enzymatic activity was caused by the enlarged accessible surface of the phosphate group binding pocket when Arg195 was mutated to His. Thus, the potential of genetic manipulation of GPAT to increase the glycerolipid level in L. incisa and other microalgae would be of great interest.

  1. Neutron crystallography of photoactive yellow protein reveals unusual protonation state of Arg52 in the crystal.

    Science.gov (United States)

    Yonezawa, Kento; Shimizu, Nobutaka; Kurihara, Kazuo; Yamazaki, Yoichi; Kamikubo, Hironari; Kataoka, Mikio

    2017-08-24

    Because of its high pKa, arginine (Arg) is believed to be protonated even in the hydrophobic environment of the protein interior. However, our neutron crystallographic structure of photoactive yellow protein, a light sensor, demonstrated that Arg52 adopts an electrically neutral form. We also showed that the hydrogen bond between the chromophore and Glu46 is a so-called low barrier hydrogen bond (LBHB). Because both the neutral Arg and LBHB are unusual in proteins, these observations remain controversial. To validate our findings, we carried out neutron crystallographic analysis of the E46Q mutant of PYP. The resultant structure revealed that the proportion of the cationic form is higher in E46Q than in WT, although the cationic and neutral forms of Arg52 coexist in E46Q. These observations were confirmed by the occupancy of the deuterium atom bound to the N η1 atom combined with an alternative conformation of the N(η2)D2 group comprising sp(2) hybridisation. Based on these results, we propose that the formation of the LBHB decreases the proton affinity of Arg52, stabilizing the neutral form in the crystal.

  2. FGFR4 Gly388Arg polymorphism and prostate cancer risk in Scottish men.

    Science.gov (United States)

    Ho, C K M; Anwar, S; Nanda, J; Habib, F K

    2010-03-01

    Fibroblast growth factor receptor 4 (FGFR4), a member of the fibroblast growth receptor family, was recently reported to be more abundantly expressed in malignant than benign prostate cells. A single nucleotide polymorphism at position 388 of the FGFR4 amino-acid sequence results in the substitution of glycine (Gly) with arginine (Arg) and higher frequency of the ArgArg genotype was previously found in prostate cancer patients. DNA was extracted from the blood drawn from 399 prostate cancer patients, 150 BPH patients and 294 healthy community controls. Polymerase chain reaction was carried out and single nucleotide polymorphisms of FGFR4 were identified by restriction enzyme digestion. No overall association is detectable between the Arg allele and increased prostate cancer risk. Subgroup analysis shows a higher incidence of the heterozygous ArgGly genotype in cancer cases than in the combined group of BPH and controls (PFGFR4 is not associated with increased risk of prostate cancer in Scottish men. This observation is in contrast with results from two previous studies conducted in the USA and Japan.

  3. Arg-Phe-amide-related peptides influence gonadotropin-releasing hormone neurons

    Institute of Scientific and Technical Information of China (English)

    Haluk Kelestimur; Emine Kacar; Aysegul Uzun; Mete Ozcan; Selim Kutlu

    2013-01-01

    The hypothalamic Arg-Phe-amide-related peptides, gonadotropin-inhibitory hormone and orthologous mammalian peptides of Arg-Phe-amide, may be important regulators of the hypothalamus-pituitary-gonadal reproductive axis. These peptides may modulate the effects of kisspeptins because they are presently recognized as the most potent activators of the hypothalamus-pituitary-gonadal axis. However, their effects on gonadotropin-releasing hormone neurons have not been investigated. In the current study, the GT1–7 cell line-expressing gonadotropin-releasing hormone was used as a model to explore the effects of Arg-Phe- amide-related peptides on kisspeptin activation. Intracellular calcium concentration was quantified using the calcium-sensitive dye, fura-2 acetoxymethyl ester. Gonadotropin-releasing hormone released into the medium was detected via enzyme-linked immunosorbent assay. Results showed that 100 nmol/L kisspeptin-10 significantly increased gonadotropin-releasing hormone levels (at 120 minutes of exposure) and intracellular calcium concentrations. Co-treatment of kisspeptin with 1 μmol/L gonadotropin-inhibitory hormone or 1 μmol/L Arg-Phe-amide-related peptide-1 significantly attenuated levels of kisspeptin-induced gonadotropin-releasing hormone but did not affect kisspeptin-induced elevations of intracellular calcium concentration. Overall, the results suggest that gonadotropin-inhibitory hormone and Arg-Phe-amide-related peptide-1 may have inhibitory effects on kisspeptin-activated gonadotropin-releasing hormone neurons independent of the calcium signaling pathway.

  4. IL23R(Arg381Gln) functional polymorphism is associated with active pulmonary tuberculosis severity.

    Science.gov (United States)

    Ben-Selma, Walid; Boukadida, Jalel

    2012-08-01

    The purpose of our study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin-23 receptor gene (IL23R; rs11209026, 1142 G(wild type) → A(reduced function), Arg381Gln) and disease severity outcome in pulmonary tuberculosis (TB) in the Tunisian population. SNP was investigated in a population of 168 patients with active pulmonary TB (cases were stratified into patients with minimal/moderate lung involvement, i.e., patients with minimal/moderate disease [Pmd], and patients with extensive lung involvement, i.e., patients with active disease [Pad]) and 150 healthy subjects. Genotype analyses were carried out using the PCR-restriction fragment length polymorphism method. We have found that the IL23R reduced-function allele 1142A and genotypes AA and AG were overrepresented, especially in the Pad subgroup compared with the control group (51% versus 18% [P = 10(-8)], 33% versus 5% [P = 10(-8)], and 36% versus 26% [P = 5 × 10(-3)], respectively). Additionally, comparison of the Pad and the Pmd groups showed that the A allele and AA genotype seemed to be associated with 2.79-fold (P = 4 × 10(-5)) and 7.74-fold (P = 10(-5)) increased risks of TB with minimal/moderate lung involvement, respectively. Our results demonstrate that the reduced-function polymorphism 1142G → A encoded by IL23R influences the outcome of disease severity of active pulmonary TB in Tunisian patients.

  5. Dominant-negative mutation p.Arg324Thr in KCNA1 impairs Kv1.1 channel function in episodic ataxia.

    Science.gov (United States)

    Tristán-Clavijo, Enriqueta; Scholl, Francisco G; Macaya, Alfons; Iglesias, Gemma; Rojas, Ana M; Lucas, Miguel; Castellano, Antonio; Martinez-Mir, Amalia

    2016-11-01

    Episodic ataxia type 1 is a rare autosomal dominant neurological disorder caused by mutations in the KCNA1 gene that encodes the α subunit of voltage-gated potassium channel Kv1.1. The functional consequences of identified mutations on channel function do not fully correlate with the clinical phenotype of patients. A clinical and genetic study was performed in a family with 5 patients with episodic ataxia type 1, with concurrent epilepsy in 1 of them. Protein expression, modeling, and electrophysiological analyses were performed to study Kv1.1 function. Whole-genome linkage and candidate gene analyses revealed the novel heterozygous mutation p.Arg324Thr in the KCNA1 gene. The encoded mutant Kv1.1 channel displays reduced currents and altered activation and inactivation. Taken together, we provide genetic and functional evidence that mutation p.Arg324Thr in the KCNA1 gene is pathogenic and results in episodic ataxia type 1 through a dominant-negative effect. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

  6. Convergent evidence of the contribution of TP53 genetic variation (Pro72Arg) to metabolic activity and white matter volume in the frontal lobe in schizophrenia patients.

    Science.gov (United States)

    Molina, Vicente; Papiol, Sergi; Sanz, Javier; Rosa, Araceli; Arias, Bárbara; Fatjó-Vilas, Mar; Calama, Julia; Hernández, Ana I; Bécker, Joemir; Fañanás, Lourdes

    2011-05-01

    Abnormalities in white matter (WM) volumes and integrity in schizophrenia, together with post-mortem studies showing reduced expression of oligodendrocyte/myelination genes and apoptotic processes taking place in oligodendrocytes, suggest the interest of major regulators of apoptosis as candidate genes for some features related to myelin integrity in schizophrenia. Protein p53, encoded by TP53 gene, has a central role in the control of apoptosis and is involved in oligodendrocyte development. TP53 gene polymorphisms may account for variability in WM features, metabolic activity and biochemical markers of neuronal integrity and membrane turnover. Pro72Arg and Ins16bp polymorphisms at TP53 gene were analyzed in 20 DSM-IV schizophrenia patients. T1/T2-weighted sequences of these patients were acquired using a 1.5T Philips Gyroscan system. Scans were transformed into Talairach space and segmented into gray matter (GM), WM and cerebrospinal fluid (CSF) using Statistical Parametric Mapping under a ROI approach. Likewise dorsolateral prefrontal cortex (DLPFC) metabolic activity was measured using a procedure based on MRI/PET image fusion. In 13 of these patients proton magnetic resonance spectroscopy was used to examine N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) levels in dorsolateral-medial prefrontal cortex (DLMPFC). MRI data were adjusted for age and brain volume using regression parameters from a healthy control group (n=45). Patients Pro/Arg heterozygous (Pro72Arg polymorphism) showed a generalized deficit in whole-brain WM that was especially prominent in frontal lobe and a lower metabolic activity in the DLPFC as compared to Pro/Pro homozygous. Pro/Arg subjects also showed decreased NAA/Cho and increased Cho/Cr ratios in right DLMPFC. TP53 genetic variability influences WM volumes in frontal lobes and it seems to modulate the metabolic activity in this region. Our results suggest that TP53 might influence aspects of myelin and white matter integrity

  7. AZT-related mutation Lys70Arg in reverse transcriptase of human immunodeficiency virus type 1 confers decrease in susceptibility to ddATP in in vitro RT inhibition assay.

    Science.gov (United States)

    Sharma, P L; Chatis, P A; Dogon, A L; Mayers, D L; McCutchan, F E; Page, C; Crumpacker, C S

    1996-09-15

    The genetic basis for didanosine (ddl) resistance in human immunodeficiency virus (HIV-1) has previously been shown to be commonly associated with a Leu to Val change at codon 74 in the HIV-1 RT gene. In this study sequential viral isolates were analyzed from five patients with prior zidovudine (AZT) use who received 6 to 16 months of ddl therapy. Following ddl therapy, viral isolates exhibited an increased AZT susceptibility and decreased ddl susceptibility. Sequence and nested PCR analysis of the HIV-1 RT gene revealed that two viral isolates contained the Leu to Val change at codon 74, and three other isolates with reduced susceptibility to ddl each contained changes at codons 65, 70, and 72. Site-directed mutagenesis was employed to insert specific mutations in RT gene of proviral clone pNL4-3. Analysis of virion-associated reverse transcriptase activity indicated that the Lys70Arg mutation resulted in an enzyme with 2- to 4-fold decreased susceptibility to ddATP. Statistical analysis of the inhibitory concentration for RT activity between pNL4-3 and mutant Lys70Arg viruses obtained in three independent RT inhibition assays was significant (P = 0.05) by student t test paired analysis. Drug susceptibility assays on the virus with Lys70Arg mutation showed a marginal decrease in susceptibility to ddl (1.5- to 2-fold) and about 4- to 6-fold decrease in susceptibility to AZT. Mutations Lys65Glu and Arg72Ser resulted in an impaired RT with greatly diminished functional RT activity. The AZT-associated Lys70Arg mutation results in an RT enzyme with decreased susceptibility to ddATP.

  8. Cloning and Bioinformatical Analysis of Phospholipase Dα1 Gene and Its Promoter in the Latex of Rubber Tree (Hevea brasiliensis Muell.Arg.)%橡胶树胶乳HbPLDα1基因及其启动子的克隆与生物信息学分析

    Institute of Scientific and Technical Information of China (English)

    夏可灿; 康桂娟; 黎瑜; 聂智毅; 代龙军; 段翠芳; 曾日中

    2012-01-01

    植物磷脂酶PLDα1与伤害信号转导密切相关,是伤害诱导内源茉莉酸(Jasmonic acid,JA)生物合成的关键酶之一.橡胶树胶乳PLDα1基因(HbPLDα1)表达的研究将有助于揭示橡胶树乳管细胞JA信号转导及其调控橡胶生物合成的机制.在EST序列的基础上,通过RACE和Genome Walking方法分别克隆了橡胶树胶乳的HbPLDα1基因及其启动子序列.HbPLDα1基因的cDNA全长为2 870 bp,包含长度为2427 bp的完整开放阅读框(ORF),具有典型的植物PLDα蛋白保守功能域,与同属大戟科的蓖麻和麻风树的PLDα1基因亲缘关系最近.HbPLDα1基因启动子区域长为1 559 bp,除含有TATA box和CAAT box等基本顺式作用元件外,还存在JA和脱落酸等激素响应元件以及干旱胁迫等环境信号响应元件,这表明HbPLDα1基因的表达可能受激素和环境信号的调控,在橡胶树乳管细胞对激素和环境信号的响应过程中发挥重要作用.%Phospholipase D alpha 1(PLDαl) is involved in wound signal transduction in plant cells, and is a key component for wound -induced jasmonic acid (JA) production. The investigation of PLDαl expression would facilitate unraveling the signaling pathway of JA and its regulation of the rubber biosynthesis in Hevea brasilienais (rubber tree). The PLDal gene from the Hevea latex, HbPLDal, and its promoter were cloned based on the EST sequences using RACE and Genome Walking. The full-length cDNA of HbPLDal gene was 2 870 bp with a complete ORF of 2 427 bp. HbPLDal had the similar typical conserved domains of plant PLD with those of other plants, and showed the highest identity with those of PLDal from Ricinus communis and Jatropha curcas. The promoter of HbPLDal was 1 559 bp long, including not only the ordinary cis-acting elements of TATA and CAAT box, but also such cis-acting elements responsive to phytohormones (JA, ABA, GB) and environmental stresses. The data demonstrated that the expressed of HbPLDal gene could be

  9. Paralysis periodica paramyotonica caused by SCN4A Arg1448Cys mutation.

    Science.gov (United States)

    Hsu, Wei-Chih; Huang, Yung-Chuan; Wang, Chung-Wei; Hsueh, Chia-Hsiang; Lai, Ling-Ping; Yeh, Jiann-Horng

    2006-06-01

    Paralysis periodica paramyotonica is an overlapping disease that shares the features of paramyotonia characteristic of paramyotonia congenita (PC) and periodic paralysis characteristic of hyperkalemic periodic paralysis. We report the case of a 23-year-old man with paralysis periodica paramyotonica. His father and a younger brother also exhibited a similar phenotype. A SCN4A Arg1448Cys mutation was detected in this family. The affected family members exhibited marked shifts in compound muscle action potential amplitudes on exercise test, and muscle weakness could be induced by potassium loading and cold exposure. This case demonstrates that SCN4A Arg1448Cys can produce paralysis periodica paramyotonica. Other genetic or environmental factors may modulate the manifestation of SCN4A Arg1448Cys mutation.

  10. Paralysis Periodica Paramyotonica Caused by SCN4A Arg1448Cys Mutation

    Directory of Open Access Journals (Sweden)

    Wei-Chih Hsu

    2006-01-01

    Full Text Available Paralysis periodica paramyotonica is an overlapping disease that shares the features of paramyotonia characteristic of paramyotonia congenita (PC and periodic paralysis characteristic of hyperkalemic periodic paralysis. We report the case of a 23-year-old man with paralysis periodica paramyotonica. His father and a younger brother also exhibited a similar phenotype. A SCN4A Arg1448Cys mutation was detected in this family. The affected family members exhibited marked shifts in compound muscle action potential amplitudes on exercise test, and muscle weakness could be induced by potassium loading and cold exposure. This case demonstrates that SCN4A Arg1448Cys can produce paralysis periodica paramyotonica. Other genetic or environmental factors may modulate the manifestation of SCN4A Arg1448Cys mutation.

  11. Pathogenic Variant in ACTB, p.Arg183Trp, Causes Juvenile-Onset Dystonia, Hearing Loss, and Developmental Delay without Midline Malformation

    Directory of Open Access Journals (Sweden)

    Erin Conboy

    2017-01-01

    Full Text Available ACTB encodes the β-actin, and pathogenic variations in this gene have typically been associated with Baraitser-Winter cerebrofrontofacial syndrome, a congenital malformation syndrome characterized by short stature, craniofacial anomalies, and cerebral anomalies. Here, we describe the third case with the p.Arg183Trp variant in ACTB causing juvenile-onset dystonia. Our patient has severe, intractable dystonia, developmental delay, and sensorineural hearing loss, besides hyperintensities in the caudate nuclei and putamen on the brain MRI, which is a distinct but overlapping phenotype with the previously reported case of identical twins with the same alteration in ACTB.

  12. Seasonal Variations in Antibiotic Resistance Gene Transport in the Almendares River, Havana, Cuba

    OpenAIRE

    Knapp, Charles W.; Lazaro eLima; Susana eOlivares-Rieumont; Emma eBowen; David eWerner; David W eGraham

    2012-01-01

    Numerous studies have quantified antibiotic resistance genes (ARG) in rivers and streams around the world, and significant relationships have been shown that relate different pollutant outputs and increased local ARG levels. However, most studies have not considered ambient flow conditions, which can vary dramatically especially in tropical countries. Here, ARG were quantified in water column and sediment samples during the dry- and wet-seasons to assess how seasonal and other factors influen...

  13. Frequencies of the Arg16Gly, Gln27Glu and Thr164Ile Adrenoceptor β2 Polymorphisms among Omanis

    Directory of Open Access Journals (Sweden)

    Khalid Al-Balushi

    2015-11-01

    Full Text Available Objectives: This study aimed to assess the distribution of missense mutations in the adrenoceptor β2 (ADRB2 gene in an Omani cohort. Methods: This study was carried out between May 2014 and March 2015 at the Sultan Qaboos University, Muscat, Oman. Blood samples were taken from 316 unrelated Omani subjects. Genotyping for rs1042713 (c.46A>G, p.Arg16Gly, rs1042714 (c.79C>G, p.Gln27Glu and rs1800888 (c.491C>T, p.Thr164Ile polymorphisms was performed by real-time polymerase chain reaction using single nucleotide polymorphism (SNP genotyping assays. The allelic frequencies of these polymorphisms were estimated on the basis of the observed numbers of specific alleles from the genotype data for male and female subjects. The genotype frequencies for each polymorphism were tested for deviation from the Hardy-Weinberg equilibrium. Results: Gly16 and Glu27 were the most frequent variants found among the cohort (63% and 75%, respectively. The Ile164 variant was not detected in the study population. There was a significant linkage disequilibrium between the rs1042713 and rs1042714 SNPs (r2 = 0.209; P ≤0.001. The most observed haplotypes were Gly16-Gln27 and Arg16-Gln27 (0.37 and 0.38, respectively. The frequency of Gly16-Glu27 was 0.25, comprising all Glu27 carriers. Conclusion: The allelic distribution of variants in this Omani cohort was similar to distributions reported among Caucasian populations.

  14. Point mutation of Arg440 to his in cytochrome P450c17 causes severe 17{alpha}-hydroxylase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Fardella, C.E.; Hum, D.W.; Miller, W.L. [Univ. of California, San Francisco, CA (United States); Homoki, J. [Univ. of Ulm (Germany)

    1994-07-01

    Genetic disorders in the gene encoding P450c17 cause 17{alpha}-hydroxylase deficiency. The consequent defects in the synthesis of cortisol and sex steroids cause sexual infantilism and a female phenotype in both genetic sexes as well as mineralorcorticoid excess and hypertension. A 15-yr-old patient from Germany was seen for absent pubertal development and mild hypertension with hypokalemia, high concentrations of 17-deoxysteroids, and hypergonadotropic hypogonadism. Analysis of her P450c17 gene by polymerase chain reaction amplification and direct sequencing showed mutation of codon 440 from CGC (Arg) to CAC (His). Expression of a vector encoding this mutated form of P450c17 in transfected nonsteroidogenic COS-1 cells showed that the mutant P450c17 protein was produced, but it lacked both 17{alpha}-hydroxylase and 17,20-lyase activities. To date, 15 different P450c17 mutations have been described in 23 patients with 17{alpha}-hydroxylase deficiency, indicating that mutations in this gene are due to random events. 36 refs., 3 figs., 2 tabs.

  15. Insulin Receptor Substrate-1 (IRS-1 Gly927Arg: Correlation with Gestational Diabetes Mellitus in Saudi Women

    Directory of Open Access Journals (Sweden)

    Khalid Khalaf Alharbi

    2014-01-01

    Full Text Available Pregnant women with gestational diabetes mellitus (GDM and type 2 diabetes mellitus (T2DM share a common pathophysiology associated with similar risk factors. Genetic variants used to determine the risk of developing T2DM might also be associated with the prevalence of GDM. The aim of the present study was to scrutinize the relationship between the G972R polymorphism of the insulin receptor substrate-1 (IRS-1 gene with GDM in the Saudi female population. This is a case-control study that monitored 500 Saudi women. Subjects with GDM (n=200 were compared with non-GDM (n=300 controls. We opted to evaluate rs1801278 polymorphism in the IRS1 gene, which plays a critical role in the insulin-signaling pathway. Genotyping was performed with the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP method. The frequency of the rs1801278 polymorphism was significantly higher in women with GDM than in women with non-GDM (for TT + CT versus CC: P=0.02. Additionally, there was a significant increase in the frequency of the Arg-encoding mutant allele from GDM to non-GDM (for T versus C: P=0.01. Our results suggest that the rs1801278 polymorphism in the IRS-1 gene is involved in the occurrence of GDM in the Saudi population.

  16. Insulin receptor substrate-1 (IRS-1) Gly927Arg: correlation with gestational diabetes mellitus in Saudi women.

    Science.gov (United States)

    Alharbi, Khalid Khalaf; Khan, Imran Ali; Abotalib, Zeinab; Al-Hakeem, Malak Mohammed

    2014-01-01

    Pregnant women with gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share a common pathophysiology associated with similar risk factors. Genetic variants used to determine the risk of developing T2DM might also be associated with the prevalence of GDM. The aim of the present study was to scrutinize the relationship between the G972R polymorphism of the insulin receptor substrate-1 (IRS-1) gene with GDM in the Saudi female population. This is a case-control study that monitored 500 Saudi women. Subjects with GDM (n = 200) were compared with non-GDM (n = 300) controls. We opted to evaluate rs1801278 polymorphism in the IRS1 gene, which plays a critical role in the insulin-signaling pathway. Genotyping was performed with the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The frequency of the rs1801278 polymorphism was significantly higher in women with GDM than in women with non-GDM (for TT + CT versus CC: P = 0.02). Additionally, there was a significant increase in the frequency of the Arg-encoding mutant allele from GDM to non-GDM (for T versus C: P = 0.01). Our results suggest that the rs1801278 polymorphism in the IRS-1 gene is involved in the occurrence of GDM in the Saudi population.

  17. Change in microbial community in landfill refuse contaminated with antibiotics facilitates denitrification more than the increase in ARG over long-term

    Science.gov (United States)

    Wu, Dong; Chen, Guanzhou; Zhang, Xiaojun; Yang, Kai; Xie, Bing

    2017-01-01

    In this study, the addition of sulfamethazine (SMT) to landfill refuse decreased nitrogen intermediates (e.g. N2O and NO) and dinitrogen (N2) gas fluxes to antibiotic resistance gene) levels in the refuse increased tenfold after long-term exposure to antibiotics, followed by a fourfold increase in the N2 flux, but SMT-amended samples with the largest resistome facilitated the denitrification (the nitrogen accumulated as NO gas at ~6 μg-N/kg-refuse·h‑1) to a lesser extent than OTC-amended samples. Further, deep sequencing results show that long-term OTC exposure partially substituted Hyphomicrobium, Fulvivirga, and Caldilinea (>5%) for the dominant bacterial hosts (Rhodothermus, ~20%) harboring nosZ and norB genes that significantly correlated with nitrogen emission pattern, while sulfamethazine amendment completely reduced the relative abundance of the “original inhabitants” functioning to produce NOx gas reduction. The main ARG carriers (Pseudomonas) that were substantially enriched in the SMT group had lower levels of denitrifying functional genes, which could imply that denitrification is influenced more by bacterial dynamics than by abundance of ARGs under antibiotic pressures.

  18. Contribution of ARLTS1 Cys148Arg (T442C variant with prostate cancer risk and ARLTS1 function in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Sanna Siltanen

    Full Text Available ARLTS1 is a recently characterized tumor suppressor gene at 13q14.3, a region frequently deleted in both sporadic and hereditary prostate cancer (PCa. ARLTS1 variants, especially Cys148Arg (T442C, increase susceptibility to different cancers, including PCa. In this study the role of Cys148Arg substitution was investigated as a risk factor for PCa using both genetic and functional analysis. Cys148Arg genotypes and expression of the ARLTS1 were explored in a large set of familial and unselected PCa cases, clinical tumor samples, xenografts, prostate cancer cell lines and benign prostatic hyperplasia (BPH samples. The frequency of the variant genotype CC was significantly higher in familial (OR = 1.67, 95% CI = 1.08-2.56, P = 0.019 and unselected patients (OR = 1.52, 95% CI = 1.18-1.97, P = 0.001 and the overall risk was increased (OR = 1.54, 95% CI = 1.20-1.98, P = 0.0007. Additional analysis with clinicopathological data revealed an association with an aggressive disease (OR = 1.28, 95% CI = 1.05-∞, P = 0.02. The CC genotype of the Cys148Arg variant was also contributing to the lowered ARLTS1 expression status in lymphoblastoid cells from familial patients. In addition significantly lowered ARLTS1 expression was observed in clinical tumor samples compared to BPH samples (P = 0.01. The ARLTS1 co-expression signature based on previously published microarray data was generated from 1587 cancer samples confirming the low expression of ARLTS1 in PCa and showed that ARLTS1 expression was strongly associated with immune processes. This study provides strong confirmation of the important role of ARLTS1 Cys148Arg variant as a contributor in PCa predisposition and a potential marker for aggressive disease outcome.

  19. 纤维蛋白原α链Arg16His突变导致遗传性异常纤维蛋白原血症%Inherited dysfibrinogenemia caused by Arg16His mutation in α chain of fibrinogen

    Institute of Scientific and Technical Information of China (English)

    赵小娟; 阮长耿; 王兆钺; 江明华; 张威; 曹丽娟; 马珍妮; 董宁征; 白霞; 余自强

    2010-01-01

    Objective To analyze the phenotype and genotype of a family with inherited dysfibrinogenemia.Methods Assays of coagulation,including activated partial thromboplastin time(APIT),prothrombin time(PT)and thrombin time(TT),were carried out with Stago Compact in the proband and his family members.The activity and antigen of fibrinogen in plasma were determined by Clanss and immunotur bidimetry,respectively.Fibrinogen and its constituent were analyzed by Western blot with nonreducing 4%-20% SDS-polyacrylamide gel electrophoresis(PAGE).All exons and exon-intron boundaries of fibringen genes FGA,FGB and FGG were analyzed by PCR and then direct sequencing.Results The proband had normal APTT and PT.but prolonged TT.The activity of fibrinogen in plasma wag decreased while its antigen level was normal.These abnormalities were also found in his mother and a sister.Genetic analysis revealed heterozygous G1233A in the exon 2 of FGA originating from his mother.which resulted in Arg16His missense mutation.Conclusion Inherited dysfibrinogenemia was caused by Arg16His mutation in exon 2 of FGA,and this iS the first case reported in a Chinese family.%目的 对1例遗传性异常纤维蛋白原血症家系进行表型和基因型分析.方法 用血凝仪检测先证者家系3代6人外周血活化部分凝血酶时间(APTT)、凝血酶原时间(PT)和凝血酶时间(TT).纤维蛋白原活性和抗原分别用Clauss法和免疫比浊法检测,Western blot检测血浆纤维蛋白原及其片段分布.PCR扩增纤维蛋白原基因FGA、FGB和FGG所有外显子及其侧翼序列,PCR产物纯化后直接测序进行基因分析.结果 先证者APTT、PT正常,而TT明显延长;纤维蛋白原抗原正常,而纤维蛋白原活性降低,先证者母亲和胞姐表型与之相似.基因分析显示先证者纤维蛋白原FGA基因2号外显子g1233→a杂合碱基改变(密码子GGT→CAT),导致Arg16His错义突变,该突变来源于母系.结论 纤维蛋白原α链Arg16His杂合错义

  20. Appearance of β-lactam Resistance Genes in Agricultural Soils and Clinical Isolates over the 20th Century

    DEFF Research Database (Denmark)

    Graham, David W.; Knapp, Charles W.; Christensen, Bent Tolstrup;

    2016-01-01

    archived since 1923 at Askov Experimental Station in Denmark, we quantified four broad-spectrum β-lactam AR genes (ARG; blaTEM, blaSHV, blaOXA and blaCTX-M) and class-1 integron genes (int1) in soils from manured (M) versus inorganic fertilised (IF) fields. “Total” β-lactam ARG levels were significantly...

  1. GABAB R活性水平对致痫大鼠认知功能及Arc/Arg3.1表达的影响%Effects of GABAB receptor expression level on cognitive impairment and Arc/Arg3.1 expression in induced epileptic rats model

    Institute of Scientific and Technical Information of China (English)

    兰彦平; 孙涛; 张春; 袁聪聪; 杨征; 王峰

    2016-01-01

    目的 探讨GABABR活性变化对癫痫大鼠认知功能及Arc/Arg3.1的影响.方法 建立氯化锂-匹罗卡品致痫模型,随机分成正常组、巴氯酚组、CGP组、单纯点燃组.避暗、水迷宫实验观察大鼠认知情况,免疫组化、荧光定量PCR、免疫印迹检测海马组织内GABABR(GB1、GB2)、Arc/Arg3.1蛋白及mRNA表达情况.结果 避暗实验:4组大鼠穿梭次数为:6.8±0.6、1.2土0.2、5.4±0.5及3.6±0.3,潜伏期为:26.1 ±3.9、152.2±12.9、65.8 ±7.0、91.2±9.1,与水迷宫行为学变化趋势一致,显示致痫大鼠认知功能减退,巴氯酚进一步抑制致痫大鼠学习和记忆获取能力,CGP35348可改善致痫大鼠认知功能.Arc/Arg3.1及GB1、GB2相对表达量检测显:致痫大鼠较正常大鼠Arc/Arg3.1及GB1、GB2表达量明显增高,致痫组大鼠相对比,巴氯酚组Arc/Arg3.1表达量下降,GB1、GB2增高;而CGP35348组Arc/Arg3.1表达量增高,GB1、GB2降低.结论 GABABR活性水平可以调控Arc/Arg3.1表达,并影响致痫大鼠认知功能.%Objective To investigate the effects of GABAB receptor on cognitive impairment by using pilocarpine induced kindled rats model and also to check early gene (Arc/Arg3.1) expression.Methods Pilocarpine induced kindled rats were divided into four groups (Group normal,Baclofen,CGP and Kindled) randomly,and every group included 20 rats.We checked their cognitive impairment by using passive avoidance test and water maze test.The expression of GABAB receptor (GB1,GB2) and Arc/Arg3.1 was tested by immunohistochemical staining,RT-PCR and Western blot.Results Passive avoidance test showed four Group rats shuttle times were 6.8 ± 0.6,1.2 ± 0.2,5.4 ± 0.5,3.6 ± 0.3,incubation period were 26.1 ±3.9,152.2 ± 12.9,65.8 ±7.0,91.2 ±9.1,and water maze test had the same trend,with values in epilepsy groups significantly lower than the normal group of rats,which meant cognitive dysfunction.The above results also showed Baclofen further inhibited the learning

  2. A ribosomal misincorporation of Lys for Arg in human triosephosphate isomerase expressed in Escherichia coli gives rise to two protein populations.

    Directory of Open Access Journals (Sweden)

    Beatriz Aguirre

    Full Text Available We previously observed that human homodimeric triosephosphate isomerase (HsTIM expressed in Escherichia coli and purified to apparent homogeneity exhibits two significantly different thermal transitions. A detailed exploration of the phenomenon showed that the preparations contain two proteins; one has the expected theoretical mass, while the mass of the other is 28 Da lower. The two proteins were separated by size exclusion chromatography in 3 M urea. Both proteins correspond to HsTIM as shown by Tandem Mass Spectrometry (LC/ESI-MS/MS. The two proteins were present in nearly equimolar amounts under certain growth conditions. They were catalytically active, but differed in molecular mass, thermostability, susceptibility to urea and proteinase K. An analysis of the nucleotides in the human TIM gene revealed the presence of six codons that are not commonly used in E. coli. We examined if they were related to the formation of the two proteins. We found that expression of the enzyme in a strain that contains extra copies of genes that encode for tRNAs that frequently limit translation of heterologous proteins (Arg, Ile, Leu, as well as silent mutations of two consecutive rare Arg codons (positions 98 and 99, led to the exclusive production of the more stable protein. Further analysis by LC/ESI-MS/MS showed that the 28 Da mass difference is due to the substitution of a Lys for an Arg residue at position 99. Overall, our work shows that two proteins with different biochemical and biophysical properties that coexist in the same cell environment are translated from the same nucleotide sequence frame.

  3. An ARGS-aggrecan assay for analysis in blood and synovial fluid

    DEFF Research Database (Denmark)

    Larsson, S; Lohmander, Stefan; Struglics, A

    2014-01-01

    OBJECTIVE: To validate a modified ligand-binding assay for the detection of aggrecanase generated aggrecan fragments with the ARGS neoepitope in synovial fluid (SF) and blood, and to verify the identity of aggrecan fragments found in blood. DESIGN: An enzyme-linked immunosorbent assay (ELISA) on ...

  4. The role of Arg445 and Asp498 in the human thyroid hormone transporter MCT8

    NARCIS (Netherlands)

    S. Groeneweg (Stefan); E.C.H. Friesema (Edith); S. Kersseboom (Simone); W. Klootwijk (Willem); W.E. Visser (Wil Edward); R.P. Peeters (Robin); T.J. Visser (Theo)

    2014-01-01

    textabstractMonocarboxylate transporter 8 (MCT8) facilitates cellular influx and efflux of the thyroid hormones (THs) T4 and T3. Mutations in MCT8 lead to severe psychomotor retardation. Here, we studied the importance of 2 highly conserved residues (Arg445 in transmembrane domain 8 and Asp498 in tr

  5. Involvement of the FGFR4 Arg388 allele in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Streit, Sylvia; Bange, Johannes; Fichtner, Alexander; Ihrler, Stephan; Issing, Wolfgang; Ullrich, Axel

    2004-08-20

    Fibroblast growth factor receptors (FGFRs) have been implicated in various forms of human hyperproliferative disorders such as cancers of the cervix and bladder. We investigated the expression pattern of FGFR4 and the clinical significance of the recently identified Gly/Arg polymorphism (388) in head and neck squamous cell carcinomas (HNSCCs) of the oral cavity and the oropharynx. Sections from 104 paraffin-embedded tumors were analyzed by a restriction fragment length polymorphism-based method to determine the FGFR4 genotypes. Protein expression was investigated immunohistochemically and graded into a low, intermediate, or high degree of staining. FGFR4 expression was scored as high in 17, as intermediate in 59 and as low in 28 cases. The FGFR4 Arg388 allele was found in 59 tumors, 46 of them having heterozygous and 13 homozygous genotypes. High expression of the FGFR4 Arg388 allele was significantly associated with reduced overall survival (p = 0.032) and with an advanced tumor stage (p = 0.023), whereas expression of the FGFR4 Gly388 had no impact on disease progression. Our findings indicate that high expression of FGFR4 in connection with the Arg388 allele is associated with poor clinical outcome and support the significance of FGFR4 as a diagnostic marker and a target for therapeutic intervention in human HNSCC.

  6. Hemoglobin Moabit: alpha 86 (F7) Leu leads to Arg: a new unstable abnormal hemoglobin.

    Science.gov (United States)

    Knuth, A; Pribilla, W; Marti, H R; Winterhalter, K H

    1979-01-01

    A new alpha chain abnormal hemoglobin variant was found in a Turkish patient with a mild Heinz body hemolytic anemia and splenomegaly. The substitution alpha 86 Leu leads to Arg, which is next to the heme binding proximal histidine, is responsible for a marked instability of the molecule. The oxygen affinity of the erythrocytes was found to be slightly decreased.

  7. The architecture of ArgR-DNA complexes at the genome-scale in> Escherichia coli

    DEFF Research Database (Denmark)

    Cho, Suhyung; Cho, Yoo-Bok; Kang, Taek Jin;

    2015-01-01

    DNA-binding motifs that are recognized by transcription factors (TFs) have been well studied; however, challenges remain in determining the in vivo architecture of TF-DNA complexes on a genome-scale. Here, we determined the in vivo architecture of Escherichia coli arginine repressor (ArgR)-DNA co...

  8. Molecular Interactions Between the Active Sites of RGD (Arg-Gly-Asp with its Receptor (Integrine

    Directory of Open Access Journals (Sweden)

    E. Jauregui

    2000-03-01

    Full Text Available A study of the molecular interactions between the active sites of RGD (Arg-Gly-Asp with it Receptor using simultaions is reported. Our calculations indicate that the guanidine-carboxylate complex is energetically favourd with respect to the guanidine-methyl tetrazole complex.

  9. A dynamic Asp-Arg interaction is essential for catalysis in microsomal prostaglandin E2 synthase.

    Science.gov (United States)

    Brock, Joseph S; Hamberg, Mats; Balagunaseelan, Navisraj; Goodman, Michael; Morgenstern, Ralf; Strandback, Emilia; Samuelsson, Bengt; Rinaldo-Matthis, Agnes; Haeggström, Jesper Z

    2016-01-26

    Microsomal prostaglandin E2 synthase type 1 (mPGES-1) is responsible for the formation of the potent lipid mediator prostaglandin E2 under proinflammatory conditions, and this enzyme has received considerable attention as a drug target. Recently, a high-resolution crystal structure of human mPGES-1 was presented, with Ser-127 being proposed as the hydrogen-bond donor stabilizing thiolate anion formation within the cofactor, glutathione (GSH). We have combined site-directed mutagenesis and activity assays with a structural dynamics analysis to probe the functional roles of such putative catalytic residues. We found that Ser-127 is not required for activity, whereas an interaction between Arg-126 and Asp-49 is essential for catalysis. We postulate that both residues, in addition to a crystallographic water, serve critical roles within the enzymatic mechanism. After characterizing the size or charge conservative mutations Arg-126-Gln, Asp-49-Asn, and Arg-126-Lys, we inferred that a crystallographic water acts as a general base during GSH thiolate formation, stabilized by interaction with Arg-126, which is itself modulated by its respective interaction with Asp-49. We subsequently found hidden conformational ensembles within the crystal structure that correlate well with our biochemical data. The resulting contact signaling network connects Asp-49 to distal residues involved in GSH binding and is ligand dependent. Our work has broad implications for development of efficient mPGES-1 inhibitors, potential anti-inflammatory and anticancer agents.

  10. The architecture of ArgR-DNA complexes at the genome-scale in Escherichia coli

    DEFF Research Database (Denmark)

    Cho, Suhyung; Cho, Yoo-Bok; Kang, Taek Jin

    2015-01-01

    R)-DNA complexes using high-throughput sequencing of exonuclease-treated chromatin-immunoprecipitated DNA (ChIP-exo). The ChIP-exo has a unique peak-pair pattern indicating 5′ and 3′ ends of ArgR-binding region. We identified 62 ArgR-binding loci, which were classified into three groups, comprising single, double...

  11. Interaction between ArgR and AhrC controls regulation of arginine metabolism in Lactococcus lactis

    NARCIS (Netherlands)

    Larsen, R; Kok, J; Kuipers, OP

    2005-01-01

    The expression of arginine metabolism in Lactococcus lactis is controlled by the two homologous transcriptional regulators ArgR and AhrC. Genome sequence analyses have shown that the occurrence of multiple homologues of the ArgR family of transcriptional regulators is a common feature of many low-G

  12. Polymorphisms in α- and β-Adrenergic Receptor Genes, Hypertension, and Obstructive Sleep Apnea: The Skaraborg Sleep Study

    Directory of Open Access Journals (Sweden)

    Kristina Bengtsson Boström

    2010-01-01

    Full Text Available The sympathetic nervous system and the adrenergic receptors play an important role in regulation of blood pressure. This study explored the associations between functional polymorphisms of the α2B-, β1-, and β2-adrenergic receptor genes and obstructive sleep apnea (OSA in hypertensive patients and hypertension in patients with OSA in a populationbased sample of 157 hypertensive patients and 181 healthy control subjects. Only the Arg389Gly polymorphism of the β1-adrenergic receptor gene was associated with increased risk for mild OSA in hypertensive patients (Arg/Arg versus Gly/Arg/Gly/Gly, 2.1, 95% CI, 1.02–4.7. Hypertensive men carrying the Arg389Arg genotype had higher crude and age-adjusted AHI than carriers of the Arg389Gly/Gly389Gly genotypes. When adjusted also for BMI this difference became borderline significant. This difference was not observed in women. The risk of hypertension in mild OSA was associated with increasing number of Arg-alleles (Arg/Arg OR 5.4, 95% CI 1.4–21.2.

  13. Antibiotic resistance genes in the bacteriophage DNA fraction of human fecal samples.

    Science.gov (United States)

    Quirós, Pablo; Colomer-Lluch, Marta; Martínez-Castillo, Alexandre; Miró, Elisenda; Argente, Marc; Jofre, Juan; Navarro, Ferran; Muniesa, Maite

    2014-01-01

    A group of antibiotic resistance genes (ARGs) (blaTEM, blaCTX-M-1, mecA, armA, qnrA, and qnrS) were analyzed by real-time quantitative PCR (qPCR) in bacteriophage DNA isolated from feces from 80 healthy humans. Seventy-seven percent of the samples were positive in phage DNA for one or more ARGs. blaTEM, qnrA, and, blaCTX-M-1 were the most abundant, and armA, qnrS, and mecA were less prevalent. Free bacteriophages carrying ARGs may contribute to the mobilization of ARGs in intra- and extraintestinal environments.

  14. Antibiotic resistance genes in municipal wastewater treatment systems and receiving waters in Arctic Canada

    DEFF Research Database (Denmark)

    Neudorf, Kara D.; Huang, Yan Nan; Ragush, Colin M.

    2017-01-01

    communities under extreme climatic conditions. WWTPs have been identified as reservoirs of antibiotic resistance genes (ARGs). The objective of this work was to quantify the presence of nine different ARG markers (int1, sul1, sul2, tet(O), erm(B), mecA, blaCTX-M, blaTEM, and qnr(S)) in two passive systems...... that the WWTPs provided only primary treatment. Low levels of the ARGs (2 log copies/mL) were observed in the effluent, demonstrating that bacteria residing in three northern WWTPs harbour ARGs conferring resistance to multiple clinically-relevant classes of antibiotics. Our results indicate that long...

  15. Diverse Phenotypic Expression of Cardiomyopathies in a Family with TNNI3 p.Arg145Trp Mutation

    Science.gov (United States)

    Hwang, Ji-won; Jang, Mi-Ae; Jang, Shin Yi; Seo, Soo Hyun; Seong, Moon-Woo; Park, Sung Sup; Ki, Chang-Seok

    2017-01-01

    Genetic diagnosis of cardiomyopathies is challenging, due to the marked genetic and allelic heterogeneity and the lack of knowledge of the mutations that lead to clinical phenotypes. Here, we present the case of a large family, in which a single TNNI3 mutation caused variable phenotypic expression, ranging from restrictive cardiomyopathy (RCMP) to hypertrophic cardiomyopathy (HCMP) to near-normal phenotype. The proband was a 57-year-old female with HCMP. Examining the family history revealed that her elder sister had expired due to severe RCMP. Using a next-generation sequencing-based gene panel to analyze the proband, we identified a known TNNI3 gene mutation, c.433C>T, which is predicted to cause an amino acid substitution (p.Arg145Trp) in the highly conserved inhibitory region of the cardiac troponin I protein. Sanger sequencing confirmed that six relatives with RCMP or near-normal phenotypes also carried this mutation. To our knowledge, this is the first genetically confirmed family with diverse phenotypic expression of cardiomyopathies in Korea. Our findings demonstrate familial implications, where a single mutation in a sarcomere protein can cause diverse phenotypic expression of cardiomyopathies.

  16. Nutrients, heavy metals and microbial communities co-driven distribution of antibiotic resistance genes in adjacent environment of mariculture.

    Science.gov (United States)

    Zhao, Zelong; Wang, Jing; Han, Ying; Chen, Jingwen; Liu, Guangfei; Lu, Hong; Yan, Bin; Chen, Shiaoshing

    2017-01-01

    With the rapid development of aquaculture, the large amounts of pollutants were discharged into the aquatic environment, where the detected antibiotic resistance genes (ARGs) have drawn increasing attention due to their potential threats to ecological environment and human health. Thus, the impact of mariculture on ARGs was assessed and the underlying mechanism of their propagation was explained. Sediments from eight sampling sites were collected along a mariculture drainage ditch, and the sediment in Yellow River Delta National Park was used as a non-mariculture control. Microbial ARGs qPCR array and illumina sequencing of 16S rRNA gene were applied to examine the changing patterns of ARGs and bacterial communities. Results showed that 18 ARGs (3 fluoroquinolone, 1 aminoglycoside, 3 macrolide-lincosamide-streptogramin B, 2 tetracycline, and 9 beta-lactam resistance genes) were influenced by mariculture, and ARGs abundance and diversity were significantly increased in mariculture sediments (p < 0.05). A remarkable shift in bacterial community structure and composition was also observed. The abundance of most of ARGs were significantly decreased in the estuary samples, implying that seawater had a significant dilution effect on the ARGs emission from the mariculture sites. Partial redundancy analysis showed that nutrients, heavy metals, and bacteria communities might directly and indirectly contribute to ARGs propagation, suggesting that the profile and dissemination of ARGs were driven by the combined effects of multiple factors in mariculture-impacted sites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Occurrence and distribution of antibiotic resistance genes in the coastal area of the Bohai Bay, China.

    Science.gov (United States)

    Niu, Zhi-Guang; Zhang, Kai; Zhang, Ying

    2016-06-15

    Considering the abuse of antibiotics worldwide, we investigated the abundance of three classes of antibiotic resistance genes (ARGs) and the concentrations of corresponding antibiotics in water and sediments of Bohai Bay. The results showed that sulI and sulII were detected in all samples, and their abundance range was 10(-5)-10(-2)/16S gene copies. The abundance of tetM and ermB were relatively higher than the other genes of tet-ARGs and erm-ARGs. Sulfonamides were the most prevalent antibiotics, and the concentrations of antibiotic in sediments were higher than those in water. The correlation analysis revealed that antibiotics had pertinence with corresponding ARGs, indicating that antibiotics play an important role in the creation and transfer of ARGs. The results of regression analysis indicated that the propagation and maintenance of sulI and sulII were facilitated by class I integrons.

  18. High-throughput profiling of antibiotic resistance genes in drinking water treatment plants and distribution systems.

    Science.gov (United States)

    Xu, Like; Ouyang, Weiying; Qian, Yanyun; Su, Chao; Su, Jianqiang; Chen, Hong

    2016-06-01

    Antibiotic resistance genes (ARGs) are present in surface water and often cannot be completely eliminated by drinking water treatment plants (DWTPs). Improper elimination of the ARG-harboring microorganisms contaminates the water supply and would lead to animal and human disease. Therefore, it is of utmost importance to determine the most effective ways by which DWTPs can eliminate ARGs. Here, we tested water samples from two DWTPs and distribution systems and detected the presence of 285 ARGs, 8 transposases, and intI-1 by utilizing high-throughput qPCR. The prevalence of ARGs differed in the two DWTPs, one of which employed conventional water treatments while the other had advanced treatment processes. The relative abundance of ARGs increased significantly after the treatment with biological activated carbon (BAC), raising the number of detected ARGs from 76 to 150. Furthermore, the final chlorination step enhanced the relative abundance of ARGs in the finished water generated from both DWTPs. The total enrichment of ARGs varied from 6.4-to 109.2-fold in tap water compared to finished water, among which beta-lactam resistance genes displayed the highest enrichment. Six transposase genes were detected in tap water samples, with the transposase gene TnpA-04 showing the greatest enrichment (up to 124.9-fold). We observed significant positive correlations between ARGs and mobile genetic elements (MGEs) during the distribution systems, indicating that transposases and intI-1 may contribute to antibiotic resistance in drinking water. To our knowledge, this is the first study to investigate the diversity and abundance of ARGs in drinking water treatment systems utilizing high-throughput qPCR techniques in China.

  19. Influence of ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms on body weight and body composition changes after a controlled weight-loss intervention.

    Science.gov (United States)

    Szendrei, Barbara; González-Lamuño, Domingo; Amigo, Teresa; Wang, Guan; Pitsiladis, Yannis; Benito, Pedro J; Gomez-Candela, Carmen; Calderón, Francisco J; Cupeiro, Rocío

    2016-03-01

    The β-2 and β-3 adrenergic receptors (ADRB2 and ADRB3) are thought to play a role in energy expenditure and lipolysis. However, the effects of the ADRB2 glutamine (Gln) 27 glutamic acid (glutamate) (Glu) and ADRB3 tryptophan (Trp) 64 arginine (Arg) polymorphisms on weight loss remain controversial. The aim of this study was to investigate the effect of these polymorphisms on changes in weight and body composition during a controlled weight-loss program. One hundred seventy-three healthy overweight and obese participants (91 women, 82 men) aged 18-50 years participated in a 22-week-long intervention based on a hypocaloric diet and exercise. They were randomly assigned to 1 of 4 groups: strength, endurance, strength and endurance combined, and physical activity recommendations only. Body weight, body mass index (BMI), and body composition variables were assessed before and after the intervention. Genetic analysis was carried out according to standard protocols. No effect of the ADRB2 gene was shown on final weight, BMI, or body composition, although in the supervised male group, Glu27 carriers tended to have greater weight (p = 0.019, 2.5 kg) and BMI (p = 0.019, 0.88 kg/m(2)) reductions than did noncarriers. There seems to be an individual effect of the ADRB3 polymorphism on fat mass (p = 0.004) and fat percentage (p = 0.036), in addition to an interaction with exercise for fat mass (p = 0.038). After the intervention, carriers of the Arg64 allele had a greater fat mass and fat percentage than did noncarriers (p = 0.004, 2.8 kg). In conclusion, the ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms may influence weight loss and body composition, although the current evidence is weak; however, further studies are necessary to clarify their roles.

  20. Effect of temperature on removal of antibiotic resistance genes by anaerobic digestion of activated sludge revealed by metagenomic approach.

    Science.gov (United States)

    Zhang, Tong; Yang, Ying; Pruden, Amy

    2015-09-01

    As antibiotic resistance continues to spread globally, there is growing interest in the potential to limit the spread of antibiotic resistance genes (ARGs) from wastewater sources. In particular, operational conditions during sludge digestion may serve to discourage selection of resistant bacteria, reduce horizontal transfer of ARGs, and aid in hydrolysis of DNA. This study applied metagenomic analysis to examine the removal efficiency of ARGs through thermophilic and mesophilic anaerobic digestion using bench-scale reactors. Although the relative abundance of various ARGs shifted from influent to effluent sludge, there was no measureable change in the abundance of total ARGs or their diversity in either the thermophilic or mesophilic treatment. Among the 35 major ARG subtypes detected in feed sludge, substantial reductions (removal efficiency >90%) of 8 and 13 ARGs were achieved by thermophilic and mesophilic digestion, respectively. However, resistance genes of aadA, macB, and sul1 were enriched during the thermophilic anaerobic digestion, while resistance genes of erythromycin esterase type I, sul1, and tetM were enriched during the mesophilic anaerobic digestion. Efflux pump remained to be the major antibiotic resistance mechanism in sludge samples, but the portion of ARGs encoding resistance via target modification increased in the anaerobically digested sludge relative to the feed. Metagenomic analysis provided insight into the potential for anaerobic digestion to mitigate a broad array of ARGs.

  1. Demonstration of the functional role of conserved Glu-Arg residues in the Staphylococcus aureus ferrichrome transporter.

    Science.gov (United States)

    Vinés, Enrique D; Speziali, Craig D; Heinrichs, David E

    2014-02-01

    The features that govern the interaction of ligand binding proteins with membrane permeases of cognate ABC transporters are largely unknown. Using sequence alignments and structural modeling based on the structure of the Escherichia coli BtuCD vitamin B12 transporter, we identified six conserved basic residues in the permease, comprised of FhuB and FhuG proteins, in the ferrichrome transporter of Staphylococcus aureus. Using alanine-scanning mutagenesis we demonstrate that two of these residues, FhuB Arg-71 and FhuG Arg-61, play a more dominant role in transporter function than FhuB Arg-74 and Arg-311, and FhuG Arg-64 and Lys-306. Moreover, we show that at positions 71 and 61 in FhuB and FhuG, respectively, arginine cannot be substituted for lysine without loss of transporter function. Previously, our laboratory demonstrated the importance of conserved acidic residues in the ferrichrome binding protein, FhuD2. Taken together, these results support the hypothesis that Glu-Arg salt bridges are critical for the interaction of the ligand binding protein with the transmembrane domains FhuB and FhuG. This hypothesis was further studied by "charge swapping" experiments whereby we constructed a S. aureus strain expressing FhuD2 with conserved residues Glu-97 and Glu-231 replaced by Arg and FhuB and FhuG with conserved basic residues Arg-71 and Arg-61, respectively, replaced by Glu. A strain containing this combination of substitutions restored partial function to the ferrichrome transporter. The results provide a direct demonstration of the functional importance of conserved basic residues on the extracellular surface of the ferrichrome permease in the Gram-positive bacterium S. aureus.

  2. Three new species of the genus Arge (Hymenoptera: Symphyta: Argidae from South Korea with key to species of the subfamily Arginae

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    Jin-Kyung Choi

    2016-06-01

    Full Text Available Three new species, Arge koreana Wei & Lee sp. nov. from South Korea, Arge pseudorejecta Wei & Lee sp. nov., and Arge shengi Wei & Lee sp. nov. from South Korea and China are described. Keys to known genera of Argidae and known species of Arginae from South Korea are provided.

  3. Hexane soluble extract of Mallotus philippensis (Lam.) Muell. Arg. root possesses anti-leukaemic activity

    OpenAIRE

    Khan, Musa; Qureshi, Rizwana Aleem; Hussain, Masroor; Mehmood, Khalid; Khan, Rahmat Ali

    2013-01-01

    Background Mallotus philippensis (Lam.) Muell. Arg. is a well known medicinal plant of Asia and Australia. Various compounds from different aerial parts of the plant have been reported possessing potent pharmacological, antiviral, antibacterial and cytotoxic activities. We were interested to determine the effects of some root extracts from M. philippensis on human promyelocytic leukemia HL-60 cell proliferation, cell cycle regulators and apoptosis in order to investigate its anti-leukemic pot...

  4. Integration of regulatory signals through involvement of multiple global regulators: control of the Escherichia coli gltBDF operon by Lrp, IHF, Crp, and ArgR

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    Mishra Pankaj K

    2007-01-01

    Full Text Available Abstract Background The glutamate synthase operon (gltBDF contributes to one of the two main pathways of ammonia assimilation in Escherichia coli. Of the seven most-global regulators, together affecting expression of about half of all E. coli genes, two were previously shown to exert direct, positive control on gltBDF transcription: Lrp and IHF. The involvement of Lrp is unusual in two respects: first, it is insensitive to the usual coregulator leucine, and second, Lrp binds more than 150 bp upstream of the transcription starting point. There was indirect evidence for involvement of a third global regulator, Crp. Given the physiological importance of gltBDF, and the potential opportunity to learn about integration of global regulatory signals, a combination of in vivo and in vitro approaches was used to investigate the involvement of additional regulatory proteins, and to determine their relative binding positions and potential interactions with one another and with RNA polymerase (RNAP. Results Crp and a more local regulator, ArgR, directly control gltBDF transcription, both acting negatively. Crp-cAMP binds a sequence centered at -65.5 relative to the transcript start. Mutation of conserved nucleotides in the Crp binding site abolishes the Crp-dependent repression. ArgR also binds to the gltBDF promoter region, upstream of the Lrp binding sites, and decreases transcription. RNAP only yields a defined DNAse I footprint under two tested conditions: in the presence of both Lrp and IHF, or in the presence of Crp-cAMP. The DNAse I footprint of RNAP in the presence of Lrp and IHF is altered by ArgR. Conclusion The involvement of nearly half of E. coli's most-global regulatory proteins in the control of gltBDF transcription is striking, but seems consistent with the central metabolic role of this operon. Determining the mechanisms of activation and repression for gltBDF was beyond the scope of this study. However the results are consistent with a

  5. Somatic mosaicism for the COL7A1 mutation p.Gly2034Arg in the unaffected mother of a patient with dystrophic epidermolysis bullosa pruriginosa.

    Science.gov (United States)

    van den Akker, P C; Pasmooij, A M G; Meijer, R; Scheffer, H; Jonkman, M F

    2015-03-01

    Dystrophic epidermolysis bullosa (DEB) is a heritable blistering disorder caused by mutations in the type VII collagen gene, COL7A1. Although revertant mosaicism is well known in DEB, 'forward' somatic mosaicism, in which a pathogenic mutation arises on a wild-type (WT) background, extending beyond the germ cells, has not been reported. It is therefore unknown what proportion of sporadic dominant DEB (DDEB) cases result from de novo mutations or somatic mosaic parents. In the clinically unaffected mother of a patient with DDEB pruriginosa due to the p.Gly2034Arg mutation, we identified the p.Gly2034Arg mutation in a proportion of lymphocytes and skin cells (mutational load 10-25%). Our data emphasize that forward mosaicism occurs in DDEB and highlight that mutation analysis should always be performed in the parents of sporadic DDEB patients to confirm the de novo status of the mutation. Ultimately, this will reveal the frequency of true de novo mutations and somatic mosaicism in parents, which has important implications for genetic counselling. Our data indicate that the threshold of mutant type VII procollagen to develop DDEB must be higher than 10-25%, which provides a rationale for therapeutic approaches aimed at increasing the WT : mutant type VII collagen ratio.

  6. Hippocampal Arc (Arg3.1) expression is induced by memory recall and required for memory reconsolidation in trace fear conditioning.

    Science.gov (United States)

    Chia, Chester; Otto, Tim

    2013-11-01

    Mounting evidence suggests that long-lasting, protein synthesis-dependent changes in synaptic strength accompany both the initial acquisition and subsequent recall of specific memories. Within brain areas thought to be important for learning and memory, including the hippocampus, learning-related plasticity is likely mediated in part by NMDA receptor activation and experience-dependent changes in gene expression. In the present study, we examined the role of activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) expression in the acquisition, recall, and reconsolidation of memory in a trace fear conditioning paradigm. First, we show that the expression of Arc protein in ventral hippocampus (VH) is dramatically enhanced by memory recall 24h after the acquisition of trace fear conditioning, and that both memory recall and the associated recall-induced enhancement of Arc expression are blocked by pre-training administration of 2-amino-5-phosphonovaleric acid (APV). Next, we show that while infusion of Arc antisense oligodeoxynucleotides (ODNs) into VH prior to testing had little effect on memory recall, it significantly reduced both Arc protein expression and freezing behavior during subsequent testing sessions. Collectively, these results suggest that Arc/Arg3.1 protein plays an important functional role in both the initial acquisition of hippocampal-dependent memory and the reconsolidation of these memories after recall. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Molecular mechanisms mediating the beneficial metabolic effects of [Arg4]tigerinin-1R in mice with diet-induced obesity and insulin resistance.

    Science.gov (United States)

    Ojo, Opeolu O; Srinivasan, Dinesh K; Owolabi, Bosede O; McGahon, Mary K; Moffett, R Charlotte; Curtis, Tim M; Conlon, J Michael; Flatt, Peter R; Abdel-Wahab, Yasser H A

    2016-08-01

    The frog skin host-defense peptide tigerinin-1R stimulates insulin release in vitro and improves glucose tolerance and insulin sensitivity in animal models of type 2 diabetes. This study extends these observations by investigating the molecular mechanisms of action underlying the beneficial metabolic effects of the analogue [Arg4]tigerinin-1R in mice with diet-induced obesity, glucose intolerance and insulin resistance. The study also investigates the electrophysiological effects of the peptide on KATP and L-type Ca2+ channels in BRIN-BD11 clonal β cells. Non-fasting plasma glucose and glucagon concentrations were significantly (pinsulin increased by twice daily treatment with [Arg4]tigerinin-1R (75 nmol/kg body weight) for 28 days. Oral and intraperitoneal glucose tolerance were significantly (pinsulin. The peptide blocked KATP channels and, consistent with this, improved beta cell responses of isolated islets to a range of secretagogues. Peptide administration resulted in up-regulation of key functional genes in islets involved insulin secretion (Abcc8, Kcnj11, Cacna1c and Slc2a2) and in skeletal muscle involved with insulin action (Insr, Irs1, Pdk1, Pik3ca, and Slc2a4). These observations encourage further development of tigerinin-1R analogues for the treatment of patients with type 2 diabetes.

  8. Mammalian neuronal actions of FMRFamide and the structurally related opioid Met-enkephalin-Arg6-Phe7.

    Science.gov (United States)

    Gayton, R J

    1982-07-15

    Since the enkephalins were first isolated a number of opioid peptides have been discovered, including a heptapeptide with the sequence Tyr-Gly-Gly-Phe-Met-Arg-Phe (Met-enkephalin-Arg6-Phe7). The heptapeptide was first isolated from chromaffin granules in bovine adrenal medulla, but using immunochemical techniques it has now been identified in human, rat and bovine brains. The C-terminal tetrapeptide of this molecule (Phe-Met-Arg-Phe) occurs in amidated form as the molluscan peptide FMRFamide. Antisera raised against FMRFamide have revealed immunoreactive material in the brains of several vertebrate species, including the rat where it occurs in nerve cell bodies and terminals. I now report that ionophoretically applied FMRFamide has an excitatory effect on rat medullary neurones which is unaffected by the opiate antagonist naloxone. In contrast, Met-enkephalin-Arg6-Phe7 and leucine-enkephalin (Leu-enkephalin) have predominantly depressant effects, which suggests that FMRFamide acts at a separate receptor.

  9. Comparative studies on the discrepant fragmentation mechanisms of the GLy-Asp-Gly-Arg and Arg-Gly-Asp-Gly: evidence for the mobile proton model.

    Science.gov (United States)

    2014-01-01

    The fragmentation mechanisms of singly protonated Gly-Asp-Gly-Arg (GDGRI and Arg-Gly-Asp-Gly (RGDGJ were investigated by mass spectrometry and theoretical methods. Both protonated molecules are fragmented mainly at the Asp-Gly amide bond C-terminal to Asp, as supported by quantum chemical calculations. Charge distributions of C and N atoms (Qc + QN) on the amide bonds were collected when the ionizing proton was fixed at different nitrogen atoms along the backbone for each peptide. Compared with the neutral molecules, the total charges of C and N atoms (Qc + QN] for the singly charged peptides tended to be negative when the proton was located at the backbone nitrogen atoms. A relatively larger value of QC + QN corresponds to a higher trend of fragmentation, which is consistent with the experimental relative abundances data that the predominant ions are y2 for [GDGR + H]+ and b3 for [RGDG + H]+. Also, the anhydride mechanism driven by the C-terminal COOH for [RGDG + H]+ was explored by a quantum-mechanical/molecular-mechanical method. Calculations indicate that the protonated peptide can be cleaved through an unusual charge-directed pathway by forming a salt bridge at the C-termini. The formation of the anhydride linkage is much more feasible since this process needs very little energy and is exother- mic, though the subsequent nucleophilic attack on the Asp carbonyl carbon is more difficult. The combined experimental and theoretical methods substantiate the mobile proton model, which opens a way to analyze quantitatively the discrepant fragmentation of dissociated peptides in peptide/protein identification.

  10. Metagenomic profiling of historic Colorado Front Range flood impact on distribution of riverine antibiotic resistance genes

    Science.gov (United States)

    Garner, Emily; Wallace, Joshua S.; Argoty, Gustavo Arango; Wilkinson, Caitlin; Fahrenfeld, Nicole; Heath, Lenwood S.; Zhang, Liqing; Arabi, Mazdak; Aga, Diana S.; Pruden, Amy

    2016-12-01

    Record-breaking floods in September 2013 caused massive damage to homes and infrastructure across the Colorado Front Range and heavily impacted the Cache La Poudre River watershed. Given the unique nature of this watershed as a test-bed for tracking environmental pathways of antibiotic resistance gene (ARG) dissemination, we sought to determine the impact of extreme flooding on ARG reservoirs in river water and sediment. We utilized high-throughput DNA sequencing to obtain metagenomic profiles of ARGs before and after flooding, and investigated 23 antibiotics and 14 metals as putative selective agents during post-flood recovery. With 277 ARG subtypes identified across samples, total bulk water ARGs decreased following the flood but recovered to near pre-flood abundances by ten months post-flood at both a pristine site and at a site historically heavily influenced by wastewater treatment plants and animal feeding operations. Network analysis of de novo assembled sequencing reads into 52,556 scaffolds identified ARGs likely located on mobile genetic elements, with up to 11 ARGs per plasmid-associated scaffold. Bulk water bacterial phylogeny correlated with ARG profiles while sediment phylogeny varied along the river’s anthropogenic gradient. This rare flood afforded the opportunity to gain deeper insight into factors influencing the spread of ARGs in watersheds.

  11. Sludge bio-drying: Effective to reduce both antibiotic resistance genes and mobile genetic elements.

    Science.gov (United States)

    Zhang, Junya; Sui, Qianwen; Tong, Juan; Buhe, Chulu; Wang, Rui; Chen, Meixue; Wei, Yuansong

    2016-12-01

    Sewage sludge is considered as one of major contributors to the increased environmental burden of ARGs. Sludge bio-drying was increasingly adopted due to its faster sludge reduction compared with composting. The fate of ARGs during full-scale sludge bio-drying was investigated to determine whether it could effectively reduce ARGs, and the contributions of bacterial community, horizontal gene transfer (HGT) through mobile genetic elements (MGEs) and co-selection from heavy metals to ARGs profiles were discussed in detail. Two piles with different aeration strategies (Pile I, the improved and Pile II, the control) were operated to elucidate effects of aeration strategy on ARGs profiles. Results showed that sludge bio-drying could effectively reduce both most of targeted ARGs (0.4-3.1 logs) and MGEs (0.8-3.3 logs) by the improved aeration strategy, which also enhanced both the sludge bio-drying performance and ARGs reduction. The enrichment of ARGs including ermF, tetX and sulII could be well explained by the evolution of bioavailable heavy metals, not HGT through MGEs, and their potential host bacteria mainly existed in Bacteroidetes. Although changes of bacterial community contributed the most to ARGs profiles, HGT through MGEs should be paid more attention especially in the thermophilic stage of sludge bio-drying.

  12. Xaa-Arg-Gly triplets in the collagen triple helix are dominant binding sites for the molecular chaperone HSP47.

    Science.gov (United States)

    Koide, Takaki; Takahara, Yoshifumi; Asada, Shinichi; Nagata, Kazuhiro

    2002-02-22

    HSP47 is an essential procollagen-specific molecular chaperone that resides in the endoplasmic reticulum of procollagen-producing cells. Recent advances have revealed that HSP47 recognizes the (Pro-Pro-Gly)(n) sequence but not (Pro-Hyp-Gly)(n) and that HSP47 recognizes the triple-helical conformation. In this study, to better understand the substrate recognition by HSP47, we synthesized various collagen model peptides and examined their interaction with HSP47 in vitro. We found that the Pro-Arg-Gly triplet forms an HSP47-binding site. The HSP47 binding was observed only when Arg residues were incorporated in the Yaa positions of the Xaa-Yaa-Gly triplets. Amino acids in the Xaa position did not largely affect the interaction. The recognition of the Arg residue by HSP47 was specific to its side-chain structure because replacement of the Arg residue by other basic amino acids decreased the affinity to HSP47. The significance of Arg residues in HSP47 binding was further confirmed by using residue-specific chemical modification of types I and III collagen. Our results demonstrate that Xaa-Arg-Gly sequences in the triple-helical procollagen molecule are dominant binding sites for HSP47 and enable us to predict HSP47-binding sites in homotrimeric procollagen molecules.

  13. Persistence of naturally occurring antibiotic resistance genes in the bacteria and bacteriophage fractions of wastewater.

    Science.gov (United States)

    Calero-Cáceres, William; Muniesa, Maite

    2016-05-15

    The emergence and prevalence of antibiotic resistance genes (ARGs) in the environment is a serious global health concern. ARGs from bacteria can be mobilized by mobile genetic elements, and recent studies indicate that phages and phage-derived particles, among others, could play a role in the spread of ARGs through the environment. ARGs are abundant in the bacterial and bacteriophage fractions of water bodies and for successful transfer of the ARGs, their persistence in these environments is crucial. In this study, three ARGs (blaTEM, blaCTX-M and sul1) that naturally occur in the bacterial and phage fractions of raw wastewater were used to evaluate the persistence of ARGs at different temperatures (4 °C, 22 °C and 37 °C) and pH values (3, 7 and 9), as well as after various disinfection treatments (thermal treatment, chlorination and UV) and natural inactivation in a mesocosm. Gene copies (GC) were quantified by qPCR; then the logarithmic reduction and significance of the differences between their numbers were evaluated. The ARGs persisted for a long time with minimal reductions after all the treatments. In general, they showed greater persistence in the bacteriophage fraction than in the bacterial fraction. Comparisons showed that the ARGs persisted under conditions that reduced culturable Escherichia coli and infectious coliphages below the limit of detection. The prevalence of ARGs, particularly in the bacteriophage fraction, poses the threat of the spread of ARGs and their incorporation into a new bacterial background that could lead to the emergence of new resistant clones.

  14. The Evolution of Regional Disparities in the Rural Areas of Muscelele Argeşului

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    CĂTĂLINA CÂRSTEA

    2012-01-01

    Full Text Available Regional disparities are clearly a significant challenge to the new European construction. Disparities are often sources of instability but are also sources of antagonism and unrest. In the case of Muscelele Argeşului, in the past, it was a unitary area in terms of economic and social development, the two Middle Ages royal capitals keeping the balance of this area. After the 50s, the situation changed radically and the uneven development of the towns and villages began to widen. Some villages were collectivized; others were industrialized, while a third category was simply omitted from the development plans. As a consequence, development disparities evolved and became common during the 80s. After 1992, around the towns of Curtea de Argeş and Câmpulung, two relatively more developed regions emerged, while regions in the north and central part of the area were disadvantaged. Beginning with 2002, we are witnessing a reduction of disparities because the underdeveloped areas are increasing and incorporate previously developed areas. The area is starting to become a huge underdeveloped area and some of the main factors that led to this situation are the decay of the two poles of regional development and the closing of the coal mines. Today, the entire area is experiencing a rebirth and the entrepreneurial activities are playing an important role. The huge number of small hotels and accommodation establishments constructed in the west part of the area in the last five years, coupled with several investment projects in Curtea de Argeş, has led to the increased regional importance of the town to the expense of Câmpulung. In the meantime, former mining centres that where the engines of growth for the region became rather underdeveloped. The main cause of this is the fact that the region does not have perspectives and lacks the much needed entrepreneurial activities.

  15. Structural and functional studies of hemoglobin Moabit (alpha 86(F7) Leu-->Arg.

    Science.gov (United States)

    Gulbis, B; Tshilolo, L; Wajcman, H; Riou, J; Galactéros, F; Promé, D; Kister, J; Papassotiriou, I; Van Laethem, Y; Vertongen, F

    1997-06-01

    An abnormal hemoglobin fraction was detected on high performance liquid chromatography profile performed for the measurement of glycated hemoglobin in a 55-year-old caucasian patient. The structural and functional studies were performed by standard techniques. Separation of hemoglobins by alkaline electrophoresis and by IEF revealed a slightly more rapid fraction than does Hb S. By acid electrophoresis, no abnormal Hb fraction could be observed. Separation of globin chains by electrophoresis demonstrated an alpha-chain variant and by chromatography, a fraction which eluted between beta and gamma globin chains. Tryptic digests and amino acid analysis have demonstrated a previously described substitution of Leu-->Arg alpha 86(F7).

  16. Rational design and characterization of D-Phe-Pro-D-Arg-derived direct thrombin inhibitors.

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    Ana C Figueiredo

    Full Text Available The tremendous social and economic impact of thrombotic disorders, together with the considerable risks associated to the currently available therapies, prompt for the development of more efficient and safer anticoagulants. Novel peptide-based thrombin inhibitors were identified using in silico structure-based design and further validated in vitro. The best candidate compounds contained both L- and D-amino acids, with the general sequence D-Phe(P3-Pro(P2-D-Arg(P1-P1'-CONH₂. The P1' position was scanned with L- and D-isomers of natural or unnatural amino acids, covering the major chemical classes. The most potent non-covalent and proteolysis-resistant inhibitors contain small hydrophobic or polar amino acids (Gly, Ala, Ser, Cys, Thr at the P1' position. The lead tetrapeptide, D-Phe-Pro-D-Arg-D-Thr-CONH₂, competitively inhibits α-thrombin's cleavage of the S2238 chromogenic substrate with a K(i of 0.92 µM. In order to understand the molecular details of their inhibitory action, the three-dimensional structure of three peptides (with P1' L-isoleucine (fPrI, L-cysteine (fPrC or D-threonine (fPrt in complex with human α-thrombin were determined by X-ray crystallography. All the inhibitors bind in a substrate-like orientation to the active site of the enzyme. The contacts established between the D-Arg residue in position P1 and thrombin are similar to those observed for the L-isomer in other substrates and inhibitors. However, fPrC and fPrt disrupt the active site His57-Ser195 hydrogen bond, while the combination of a P1 D-Arg and a bulkier P1' residue in fPrI induce an unfavorable geometry for the nucleophilic attack of the scissile bond by the catalytic serine. The experimental models explain the observed relative potency of the inhibitors, as well as their stability to proteolysis. Moreover, the newly identified direct thrombin inhibitors provide a novel pharmacophore platform for developing antithrombotic agents by exploring the

  17. Estudo anatômico do lenho de Sapium haematospermum Müll. Arg. (Euphorbiaceae)

    OpenAIRE

    Siegloch, Anelise Marta; Marchiori, José Newton Cardoso; Universidade Federal de Santa Maria; Santos, Sidinei Rodrigues dos

    2014-01-01

    No presente estudo é descrito o lenho de Sapium haematospermum Müll. Arg., com base em material procedente de São Francisco de Assis, Rio Grande do Sul. Foram observadas as seguintes características anatômicas, comuns em Euphorbioideae e gênero Sapium: anéis de crescimento pouco conspícuos; poros de diâmetro médio, pouco numerosos e em curtos múltiplos radiais; placas de perfuração simples; pontoações intervasculares grandes; parênquima apotraqueal difuso-em-agregados; e raios uni e bisseriad...

  18. Biologia reprodutiva de Psychotria poeppigiana Mull. Arg. (Rubiaceae em mata de galeria Reproductive biology of Psychotria poeppigiana Mull. Arg. (Rubiaceae in gallery forest

    Directory of Open Access Journals (Sweden)

    Christiano Peres Coelho

    2004-09-01

    Full Text Available Psychotria L. (Rubiaceae é o gênero com mais espécies heterostílicas dentre as Angiospermas. O objetivo deste trabalho é descrever a biologia floral, fenologia, o sistema reprodutivo e os polinizadores de Psychotria poeppigiana Müll. Arg. As inflorescências são capitadas terminais, com brácteas vermelhas e flores amarelas apresentando dois morfos distintos: brevistiladas e longistiladas, caracterizadas por flores hermafroditas com diferentes comprimentos de estiletes e posicionamento oposto das anteras (hercogamia recíproca. Encontrou-se diferenças no tamanho das anteras, dos grãos de pólen e da superfície estigmática entre os morfotipos. Polinizações controladas mostraram que os morfotipos apresentam auto-incompatibilidade e intramorfo-incompatibilidade ao nível do estigma e do estilete. Os visitantes são pequenas vespas, abelhas, borboletas e beija-flores, que visitam as flores com maior freqüência no início da manhã. De acordo com a freqüência e eficiência no comportamento de transportar os grãos de pólen entre os morfos florais, o principal polinizador foi o beija-flor Thalurania furcata. O néctar é produzido em pequena quantidade (máximo de 8µl e durante a abertura das flores, que ocorre entre 5 e 7h. A espécie forma agrupamentos devido à existência de reprodução vegetativa.Psychotria L. (Rubiaceae is the genus with the most heterostylous species in the angiosperms. The objective of this study is to describe floral biology, phenology, reproductive system, and pollinators of Psychotria poeppigiana Müll. Arg. The terminal inflorescences are capitate with red bracts and yellow flowers, and presented two different morphs: pin and thrum, characterized by hermaphroditic flowers with different lengths of styles and opposed position of the anthers (reciprocal herkogamy. Dimorphism was also observed in the size of anthers, pollen grains and stigmatic surfaces. Controlled pollination revealed self

  19. Chapa aglomerada de cimento-madeira de Hevea brasiliensis Müll. Arg. Cement-bonded particleboard of Hevea brasiliensis Müll. Arg.

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    Esmeralda Yoshico Arakaki Okino

    2004-06-01

    Full Text Available Chapas de partículas de cimento-madeira foram confeccionadas com a madeira de quatro clones de Hevea brasiliensis Müll. Arg. (seringueira: IAN 717, IAN 873, GT 711 e AVROS 1301. Confeccionaram-se as chapas na proporção de 1:4:1 (madeira:cimento:água por peso e nas dimensões de 450 x 450 x 13 mm e densidade nominal de 1,4 g/cm³, com a adição de 4% de cloreto de cálcio di-hidratado (CaCl2.2H2O como acelerador. Foram testadas partículas fervidas e não-fervidas dos quatro clones, totalizando oito tratamentos, sendo em cada um destes, com quatro repetições, avaliadas as propriedades mecânicas e físicas das chapas, segundo a norma ASTM D 1037 - 96a. De forma geral, os melhores resultados de propriedades físicas e mecânicas foram obtidos nas chapas com partículas do clone AVROS 1301. No teste de hidratação do cimento, a madeira de seringueira in natura foi classificada como de "inibição extrema", porém com a adição de CaCl2 o foi como de "baixa inibição". Essa madeira se mostrou tecnicamente viável à produção de chapas de cimento-madeira, independentemente do clone.Cement-bonded particleboards of rubberwood were manufactured with four clones of Hevea brasiliensis Müll. Arg. (rubberwood: IAN 717, IAN 873, GT 711 and AVROS 1301. Boards of 450 x 450 x 13 mm were manufactured in a ratio of 1:4:1 (wood/cement/water, weight basis, with 1.4 g/cm³ density and 4% calcium chloride dihydrated - CaCl2.2H2O as accelerator. The particles of four clones were tested in treated and untreated conditions, totaling eight treatments. In each treatment with four replicates, the physical and mechanical properties were evaluated according to ASTM D 1037 - 96a standard. Overall, the best mechanical and physical results were obtained with the cement-bonded particleboard made with particles from clone AVROS 1301. Rubberwood has shown to be "highly inhibitory" in the hydration test, however when CaCl2 was added the inhibition index decreased and

  20. Effects of advanced treatment systems on the removal of antibiotic resistance genes in wastewater treatment plants from Hangzhou, China.

    Science.gov (United States)

    Chen, Hong; Zhang, Mingmei

    2013-08-06

    This study aimed at quantifying the concentration and removal of antibiotic resistance genes (ARGs) in three municipal wastewater treatment plants (WWTPs) employing different advanced treatment systems [biological aerated filter, constructed wetland, and ultraviolet (UV) disinfection]. The concentrations of tetM, tetO, tetQ, tetW, sulI, sulII, intI1, and 16S rDNA genes were examined in wastewater and biosolid samples. In municipal WWTPs, ARG reductions of 1-3 orders of magnitude were observed, and no difference was found among the three municipal WWTPs with different treatment processes (p > 0.05). In advanced treatment systems, 1-3 orders of magnitude of reductions in ARGs were observed in constructed wetlands, 0.6-1.2 orders of magnitude of reductions in ARGs were observed in the biological aerated filter, but no apparent decrease by UV disinfection was observed. A significant difference was found between constructed wetlands and biological filter (p constructed wetlands and UV disinfection (p constructed wetlands, significant correlations were observed in the removal of ARGs and 16S rDNA genes (R(2) = 0.391-0.866; p Constructed wetlands not only have the comparable ARG removal values with WWTP (p > 0.05) but also have the advantage in ARG relative abundance removal, and it should be given priority to be an advanced treatment system for further ARG attenuation from WWTP.

  1. Narrow grass hedges reduce tylosin and associated antimicrobial resistance genes in agricultural runoff

    Science.gov (United States)

    Agricultural runoff from areas receiving livestock manure can potentially contaminate surface water with antimicrobials and antimicrobial resistance genes (ARGs). The objective of this study was to investigate the effectiveness of narrow grass hedges (NGHs) on reducing the transport of antimicrobial...

  2. TGFbeta1 (Leu10Pro), p53 (Arg72Pro) can predict for increased risk for breast cancer in south Indian women and TGFbeta1 Pro (Leu10Pro) allele predicts response to neo-adjuvant chemo-radiotherapy.

    Science.gov (United States)

    Rajkumar, Thangarajan; Samson, Mani; Rama, Ranganathan; Sridevi, Veluswami; Mahji, Urmila; Swaminathan, Rajaraman; Nancy, Nirmala K

    2008-11-01

    The breast cancer incidence has been increasing in the south Indian women. A case (n=250)-control (n=500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in GSTM1 (Present/Null); GSTP1 (Ile105Val), p53 (Arg72Pro), TGFbeta1 (Leu10Pro), c-erbB2 (Ile655Val), and GSTT1 (Null/Present) in breast cancer. In addition, the value of the SNP's in predicting primary tumor's pathologic response following neo-adjuvant chemo-radiotherapy was assessed. Genotyping was done using PCR (GSTM1, GSTT1), Taqman Allelic discrimination assay (GSTP1, c-erbB2) and PCR-CTPP (p53 and TGFbeta1). None of the gene SNP's studied were associated with a statistically significant increased risk for the breast cancer. However, combined analysis of the SNP's showed that p53 (Arg/Arg and Arg/Pro) with TGFbeta1 (Pro/Pro and Leu/Pro) were associated with greater than 2 fold increased risk for breast cancer in Univariate (P=0.01) and Multivariate (P=0.003) analysis. There was no statistically significant association for the GST family members with the breast cancer risk. TGFbeta1 (Pro/Pro) allele was found to predict complete pathologic response in the primary tumour following neo-adjuvant chemo-radiotherapy (OR=6.53 and 10.53 in Univariate and Multivariate analysis respectively) (P=0.004) and was independent of stage. This study suggests that SNP's can help predict breast cancer risk in south Indian women and that TGFbeta1 (Pro/Pro) allele is associated with a better pCR in the primary tumour.

  3. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  4. THE INCIDENCE OF HIV INFECTIONS IN ARGES POPULATION IN 2012 - 2013

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    Ionica Deliu

    2015-12-01

    Full Text Available Human immunodeficiency virus (HIV from Retroviridae family was isolated in early 80´s but his presence in Africa is much older than we previously thought, before the pandemic spread because of the social changes of 70´s (Cernescu, 1998. The incidence of HIV infections is a constant concern for public health specialists, with inferences for whole population. In this paper we presented the incidence of HIV infections in 2012/2013 period in Arges County, Romania. Studies were made in Laboratories of Public Health Department Arges. Immunoenzymatic methods were used for anti-HIV antibodies detection (Genscreen ULTRA HIV Ag-Ab kit from BIO RAD. The results of the immunoenzymatic tests were presented in order to age and gender of the tested people. New cases of HIV infection were 1.73% in 2012 and 1.10% in 2013 from all investigated samples. The positive samples were frequent in male population, and for 25 -34 years and 35-44 years age groups. Prophylaxis is the best weapon in fight against HIV/AIDS. But the properly way to stop the spread of HIV infections may be the development of vaccine or drugs to stop progression to AIDS (Al-Jabri, 2007.

  5. Ablation of Arg-tRNA-protein transferases results in defective neural tube development.

    Science.gov (United States)

    Kim, Eunkyoung; Kim, Seonmu; Lee, Jung Hoon; Kwon, Yong Tae; Lee, Min Jae

    2016-08-01

    The arginylation branch of the N-end rule pathway is a ubiquitin-mediated proteolytic system in which post-translational conjugation of Arg by ATE1-encoded Arg-tRNA-protein transferase to N-terminal Asp, Glu, or oxidized Cys residues generates essential degradation signals. Here, we characterized the ATE1-/- mice and identified the essential role of N-terminal arginylation in neural tube development. ATE1-null mice showed severe intracerebral hemorrhages and cystic space near the neural tubes. Expression of ATE1 was prominent in the developing brain and spinal cord, and this pattern overlapped with the migration path of neural stem cells. The ATE1-/- brain showed defective G-protein signaling. Finally, we observed reduced mitosis in ATE1-/- neuroepithelium and a significantly higher nitric oxide concentration in the ATE1-/- brain. Our results strongly suggest that the crucial role of ATE1 in neural tube development is directly related to proper turn-over of the RGS4 protein, which participate in the oxygen-sensing mechanism in the cells. [BMB Reports 2016; 49(8): 443-448].

  6. Apolipoprotein E4 domain interaction accelerates diet-induced atherosclerosis in hypomorphic Arg-61 Apoe mice

    Science.gov (United States)

    Eberlé, Delphine; Kim, Roy Y.; Luk, Fu Sang; de Mochel, Nabora Soledad Reyes; Gaudreault, Nathalie; Olivas, Victor R.; Kumar, Nikit; Posada, Jessica M.; Birkeland, Andrew C.; Rapp, Joseph H.; Raffai, Robert L.

    2012-01-01

    Objective Apolipoprotein (apo) E4 is an established risk factor for atherosclerosis, but the structural components underlying this association remain unclear. ApoE4 is characterized by two biophysical properties: domain interaction and molten globule state. Substituting Arg-61 for Thr-61 in mouse apoE introduces domain interaction without molten globule state, allowing us to delineate potential pro-atherogenic effects of domain interaction in vivo. Methods and Results We studied atherosclerosis susceptibility of hypomorphic Apoe mice expressing either Thr-61 or Arg-61 apoE (ApoeTh/h or ApoeRh/h mice). On a chow diet, both mouse models were normo-lipidemic with similar levels of plasma apoE and lipoproteins. However, on a high cholesterol diet, ApoeRh/h mice displayed increased levels of total plasma cholesterol and VLDL as well as larger atherosclerotic plaques in the aortic root, arch and descending aorta compared to ApoeTh/h mice. In addition, evidence of cellular dysfunction was identified in peritoneal ApoeRh/h macrophages which released lower amounts of apoE in culture medium and displayed increased expression of MHC class II molecules. Conclusions These data indicate that domain interaction mediates pro-atherogenic effects of apoE4 in part by modulating lipoprotein metabolism and macrophage biology. Pharmaceutical targeting of domain interaction could lead to new treatments for atherosclerosis in apoE4 individuals. PMID:22441102

  7. VIDRARU RESERVOIR, ROMANIA. ENVIRONMENTAL IMPACT OF THE HYDROTEHNICAL CONSTRUCTIONS ON THE UPPER COURSE OF ARGES RIVER

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    Laura Ana MITITELU

    2010-12-01

    Full Text Available Having an important hydrographic system, with a significant discharge potential and being located in a place that has all the forms of relief, the basin Arges is, at present, one of the most complex hydroelectric facilities from all the rivers with reservoirs in the country. Vidraru reservoir is the biggest of its 11 reservoirs. The information (data about the management of the water in Walachia dates from the year 1576, and the oldest writing about protection against floods is known as the “Ipsilantis canal”, which stated that the big waters of Dambovita river were deviated at Lunguletu in the riverbed of Ciorogarla rivulet and dates from 1774.The effects caused by the hydrotehnical constructions on the environment are numerous and profound, both positive and negative. In this essay, the analysis of the environmental impact of the hydrotehnical facilities on Arges River is made from two perspectives. The first method of analysis is the Water Directive 2000/60 and the second method is basd on a SWOT analysis, a method taken from the economy, but very efficient in establishing the current state, and also the perpective of this environemental impact.

  8. Mutation of Arg154 to Gly154 in urokinase augments its fibrin-specificity.

    Science.gov (United States)

    Peng, G; Ma, Z; Kuai, L; Zhu, D

    1997-04-01

    Rscu-PA and its mutant constructed by in vitro site specific mutagenesis of Arg154 in rscu-PA to Gly154 (mscu-PA) were both expressed in Escherichia coli. After in vitro denaturation and renaturation, the rscu-PA and mscu-PA were purified to homogeneity by Zn2+ selective precipitation, anti-u-PA IgG-sepharose CL 4B affinity chromatography. After activation by plasmin, the kinetic constants for the resultant mtcu-PA against synthetic substrate S2444 hydrolysis were found to be essentially identical to rtcu-PA, suggesting that no impairment had been exerted on the catalytic active site of mtcu-PA. However, both 125I-fibrin plasma-clot lysis and fibrinogenolysis showed that mtcu-PA possessed a higher fibrinolytic activity but hardly any degradation of fibrinogen in plasma compared to rtcu-PA and rscu-PA. It was concluded that the substitution of Arg154 by Gly154 in tcu-PA promoted the fibrin-specificity of urokinase.

  9. Arg-Tyr-Asp (RYD) and Arg-Cys-Asp (RCD) motifs in dendroaspin promote selective inhibition of beta1 and beta3 integrins.

    Science.gov (United States)

    Wattam, B; Shang, D; Rahman, S; Egglezou, S; Scully, M; Kakkar, V; Lu, X

    2001-05-15

    Arg-Gly-Asp (RGD) is a unique minimal integrin-binding sequence that is found within several glycoprotein ligands. This sequence has also been found in snake-venom anti-platelet proteins, including the disintegrins and dendroaspin, a natural variant of short-chain neurotoxins isolated from the venom of Dendroaspis jamesonii. In the present study, the motifs RYD and RCD were introduced into the dendroaspin scaffold to replace RGD. Both motifs in dendroaspin caused inhibition of ADP-induced platelet aggregation with IC(50) values of 200 and 300 nM respectively, similar to that of the wild-type RGD motif (170 nM). In comparison with wild-type dendroaspin, both RYD- and RCD-containing dendroaspins were more selective in the inhibition of the adhesion of K562 cells to laminin rather than to fibrinogen and fibronectin, even though they were 10-30-fold less potent at inhibiting K562 cell (containing alpha(5)beta(1) integrin) adhesion to laminin compared with wild-type. Interestingly, the RYD motif produced a similar IC(50) value to the RGD motif at inhibiting A375-SM cell (beta(3) integrin) adhesion to collagen, whereas the RCD motif was approx. 2-6-fold less potent compared with either RGD or RYD. These findings show that the selectivity of dendroaspin binding to beta(1) and beta(3) integrins can be modulated by the introduction of alternative cell recognition sequences.

  10. The Topology of the l-Arginine Exporter ArgO Conforms to an Nin-Cout Configuration in Escherichia coli: Requirement for the Cytoplasmic N-Terminal Domain, Functional Helical Interactions, and an Aspartate Pair for ArgO Function.

    Science.gov (United States)

    Pathania, Amit; Gupta, Arvind Kumar; Dubey, Swati; Gopal, Balasubramanian; Sardesai, Abhijit A

    2016-12-01

    ArgO and LysE are members of the LysE family of exporter proteins and ordinarily mediate the export of l-arginine (Arg) in Escherichia coli and l-lysine (Lys) and Arg in Corynebacterium glutamicum, respectively. Under certain conditions, ArgO also mediates Lys export. To delineate the arrangement of ArgO in the cytoplasmic membrane of E. coli, we have employed a combination of cysteine accessibility in situ, alkaline phosphatase fusion reporters, and protein modeling to arrive at a topological model of ArgO. Our studies indicate that ArgO assumes an Nin-Cout configuration, potentially forming a five-transmembrane helix bundle flanked by a cytoplasmic N-terminal domain (NTD) comprising roughly its first 38 to 43 amino acyl residues and a short periplasmic C-terminal region (CTR). Mutagenesis studies indicate that the CTR, but not the NTD, is dispensable for ArgO function in vivo and that a pair of conserved aspartate residues, located near the opposing edges of the cytoplasmic membrane, may play a pivotal role in facilitating transmembrane Arg flux. Additional studies on amino acid substitutions that impair ArgO function in vivo and their derivatives bearing compensatory amino acid alterations indicate a role for intramolecular interactions in the Arg export mechanism, and some interactions are corroborated by normal-mode analyses. Lastly, our studies suggest that ArgO may exist as a monomer in vivo, thus highlighting the requirement for intramolecular interactions in ArgO, as opposed to interactions across multiple ArgO monomers, in the formation of an Arg-translocating conduit.

  11. On-site removal of antibiotics and antibiotic resistance genes from leachate by aged refuse bioreactor: Effects of microbial community and operational parameters.

    Science.gov (United States)

    Su, Yinglong; Wang, Jiaxin; Huang, Zhiting; Xie, Bing

    2017-07-01

    The abuse of antibiotics has raised the prevalence of antibiotic resistance, which will pose potential risk to human health. Leachate, generated during the landfill treatment of municipal solid waste, is the important hotspot of the antibiotics and antibiotic resistance genes (ARGs), and no effective on-site treatment has been put forward for preventing ARGs dissemination. Herein, the aged refuse bioreactor was employed to remove antibiotics and ARGs from leachate, and the great removal performance was observed. For the detected antibiotics, the total removal efficiency was about 76.75%, and sulfanilamide and macrolide were removed with high efficiencies (>80%). Among the target ARGs, tetracycline and macrolide resistance genes (tetM, tetQ and ermB) were eliminated with 1.2-2.0 orders of magnitude. The occurrences of ARGs did not correlated with water quality parameters such as COD, total nitrogen, ammonia, nitrate and nitrite, but closely linked to the variations of the bacterial community structure. Redundancy analysis (RDA) indicated the significant correlations between four genera and the distribution of ARGs, which implied that these key genera (including potential pathogens) drove the ARGs removal. Furthermore, the hydraulic loading test confirmed that the aged refuse bioreactor was capable of achieving high removal efficiencies even under shock loading for the higher loading was negative for the proliferations of potential ARGs hosts. This study suggested that aged refuse bioreactor could be a promising way for antibiotics and ARGs on-site removal from leachate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Comparative MD Simulations Indicate a Dual Role for Arg1323.50 in Dopamine-Dependent D2R Activation.

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    Ralf C Kling

    Full Text Available Residue Arg3.50 belongs to the highly conserved DRY-motif of class A GPCRs, which is located at the bottom of TM3. On the one hand, Arg3.50 has been reported to help stabilize the inactive state of GPCRs, but on the other hand has also been shown to be crucial for stabilizing active receptor conformations and mediating receptor-G protein coupling. The combined results of these studies suggest that the exact function of Arg3.50 is likely to be receptor-dependent and must be characterized independently for every GPCR. Consequently, we now present comparative molecular-dynamics simulations that use our recently described inactive-state and Gα-bound active-state homology models of the dopamine D2 receptor (D2R, which are either bound to dopamine or ligand-free, performed to identify the function of Arg1323.50 in D2R. Our results are consistent with a dynamic model of D2R activation in which Arg1323.50 adopts a dual role, both by stabilizing the inactive-state receptor conformation and enhancing dopamine-dependent D2R-G protein coupling.

  13. Novel R-plasmid conjugal transfer inhibitory and antibacterial activities of phenolic compounds from Mallotus philippensis (Lam.) Mull. Arg.

    Science.gov (United States)

    Oyedemi, Blessing O M; Shinde, Vaibhav; Shinde, Kamlesh; Kakalou, Dionysia; Stapleton, Paul D; Gibbons, Simon

    2016-06-01

    Antimicrobial resistance severely limits the therapeutic options for many clinically important bacteria. In Gram-negative bacteria, multidrug resistance is commonly facilitated by plasmids that have the ability to accumulate and transfer refractory genes amongst bacterial populations. The aim of this study was to isolate and identify bioactive compounds from the medicinal plant Mallotus philippensis (Lam.) Mull. Arg. with both direct antibacterial properties and the capacity to inhibit plasmid conjugal transfer. A chloroform-soluble extract of M. philippensis was subjected to bioassay-guided fractionation using chromatographic and spectrometric techniques that led to the isolation of the known compounds rottlerin [5,7-dihydroxy-2,2-dimethyl-6-(2,4,6-trihydroxy-3-methyl-5-acetylbenzyl)-8-cinnamoyl-1,2-chromene] and the red compound (8-cinnamoyl-5,7-dihydroxy-2,2,6-trimethylchromene). Both compounds were characterised and elucidated using one-dimensional and two-dimensional nuclear magnetic resonance (NMR). Rottlerin and the red compound showed potent activities against a panel of clinically relevant Gram-positive bacteria, including meticillin-resistant Staphylococcus aureus (MRSA). No significant direct activities were observed against Gram-negative bacteria. However, both rottlerin and the red compound strongly inhibited conjugal transfer of the plasmids pKM101, TP114, pUB307 and R6K amongst Escherichia coli at a subinhibitory concentration of 100mg/L. Interestingly, despite the planar nature of the compounds, binding to plasmid DNA could not be demonstrated by a DNA electrophoretic mobility shift assay. These results show that rottlerin and the red compound are potential candidates for antibacterial drug lead development. Further studies are needed to elucidate the mode of inhibition of the conjugal transfer of plasmids.

  14. Effect of cessation of beef cattle pasture-feedlot type backgrounding operation on the persistence of antibiotic resistance genes in the environment

    Science.gov (United States)

    Introduction It is not known how removal of cattle from a backgrounding operation will affect the persistence of antibiotic resistance genes (ARGs) in the environment. Our objective was to investigate the effect of destocking on the persistence and distribution of ARGs in the backgrounding environm...

  15. [Preliminary studies on the occurrence of antibiotic resistance genes in typical aquaculture area of the Pearl River Estuary].

    Science.gov (United States)

    Liang, Xi-Mei; Nie, Xiang-Ping; Shi, Zhen

    2013-10-01

    Traditional and quantitative PCR techniques were used to determine the occurrence and quantities of ARGs, including three types of genes resistant to sulfonamide, seven for tetracycline resistance and one for quinolone resistance, as well as one integron gene in typical aquaculture of the Pearl River Estuary. The results showed that all genes except for tetW were detectable in the aquaculture environment, and sull, sul2 and int1 were the most frequently detected genes (detectable percentage, 100% ). Relative abundances of ARGs increased with the prolongation of rearing time under the same aquaculture pattern, suggesting a cumulative effect. Moreover, the occurrences of ARGs in the ponds were different with different aquaculture patterns, indicating that the aquaculture pattern might play an important role in the abundances and distributions of ARGs. Relative abundances of intl, as a horizontal mobile genetic element, were significantly correlated to the levels of sull and the total ARGs (P aquaculture substantially increased the abundances of ARGs probably owning to the induction of horizontal gene transfer of ARGs among bacteria.

  16. Intratympanic delivery of oligoarginine-conjugated nanoparticles as a gene (or drug) carrier to the inner ear.

    Science.gov (United States)

    Yoon, Ji Young; Yang, Keum-Jin; Kim, Da Eun; Lee, Kyu-Yup; Park, Shi-Nae; Kim, Dong-Kee; Kim, Jong-Duk

    2015-12-01

    A drug delivery system to the inner ear using nanoparticles consisting of oligoarginine peptide (Arg8) conjugated to poly(amino acid) (poly(2-hydroxyethyl L-aspartamide; PHEA) was investigated to determine whether the limitations of low drug transport levels across the round window membrane (RWM) and poor transport into inner ear target cells, including hair cells and spiral ganglion, could be overcome. Three types of carrier materials, PHEA-g-C18, PHEA-g-Arg8, and PHEA-g-C18-Arg8, were synthesized to examine the effects of oligoarginine and morphology of the synthesized carriers. Nile red (NR) was used as a fluorescent indicator as well as to model a hydrophobic drug. Compared with PHEA-g-C18-NR nanoparticles, the oligoarginine-conjugated nanoparticles of PHEA-g-C18-Arg8-NR and PHEA-g-Arg8-NR entered into HEI-OC1 cells at significant levels. Furthermore, the strongest fluorescence intensity was observed in nuclei when PHEA-g-C18-Arg8 nanoparticles were used. The high uptake rates of PHEA-g-C18 and PHEA-g-C18-Arg8 nanoparticles were observed in ex vivo experiments using hair cells. After the delivery of PHEA-g-C18-Arg8 nanoparticles with reporter gene transfer, EGFP (enhanced green fluorescent protein) expression was monitored as an indicator of gene delivery. In the inner ear cells, PHEA-g-C18-Arg8 nanoparticles showed comparable or better transfection capabilities than the commercially available Lipofectamine reagent. PHEA-g-C18-Arg8 penetrated in vivo across the RWM of C57/BL6 mice with Nile red staining and GFP expression in various inner ear tissues. In conclusion, PHEA-g-C18-Arg8 nanoparticles were successfully transported into the inner ear through the intratympanic route and are proposed as promising candidates as delivery carriers to address inner ear diseases.

  17. Temporal succession of soil antibiotic resistance genes following application of swine, cattle and poultry manures spiked with or without antibiotics.

    Science.gov (United States)

    Zhang, Yu-Jing; Hu, Hang-Wei; Gou, Min; Wang, Jun-Tao; Chen, Deli; He, Ji-Zheng

    2017-09-27

    Land application of animal manure is a common agricultural practice potentially leading to dispersal and propagation of antibiotic resistance genes (ARGs) in environmental settings. However, the fate of resistome in agro-ecosystems over time following application of different manure sources has never been compared systematically. Here, soil microcosm incubation was conducted to compare effects of poultry, cattle and swine manures spiked with or without the antibiotic tylosin on the temporal changes of soil ARGs. The high-throughput quantitative PCR detected a total of 185 unique ARGs, with Macrolide-Lincosamide-Streptogramin B resistance as the most frequently encountered ARG type. The diversity and abundance of ARGs significantly increased following application of manure and manure spiked with tylosin, with more pronounced effects observed in the swine and poultry manure treatments than in the cattle manure treatment. The level of antibiotic resistance gradually decreased over time in all manured soils but was still significantly higher in the soils treated with swine and poultry manures than in the untreated soils after 130 days' incubation. Tylosin-amended soils consistently showed higher abundances of ARGs than soils treated with manure only, suggesting a strong selection pressure of antibiotic-spiked manure on soil ARGs. The relative abundance of ARGs had significantly positive correlations with integrase and transposase genes, indicative of horizontal transfer potential of ARGs in manure and tylosin treated soils. Our findings provide evidence that application of swine and poultry manures might enrich more soil ARGs than cattle manure, which necessitates the appropriate treatment of raw animal manures prior to land application to minimise the spread of environmental ARGs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model

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    Matsubara Tsukasa

    2010-09-01

    Full Text Available Abstract Background The anti-human Fas/APO-1/CD95 (Fas mouse/human chimeric monoclonal IgM antibody ARG098 (ARG098 targets the human Fas molecule. The cytotoxic effects of ARG098 on cells isolated from RA patients, on normal cells in vitro, and on RA synovial tissue and cartilage in vivo using implanted rheumatoid tissues in an SCID mouse model (SCID-HuRAg were investigated to examine the potential of ARG098 as a therapy for RA. Methods ARG098 binding to each cell was analyzed by cytometry. The effects of ARG098 on several cells were assessed by a cell viability assay in vitro. Effects on the RA synovium, lymphocytes, and cartilage were assessed in vivo using the SCID-HuRAg mouse model. Results ARG098 bound to cell surface Fas molecules, and induced apoptosis in Fas-expressing RA synoviocytes and infiltrating lymphocytes in the RA synovium in a dose-dependent manner. However, ARG098 did not affect the cell viability of peripheral blood mononuclear cells of RA patients or normal chondrocytes. ARG098 also induced apoptosis in RA synoviocytes and infiltrating lymphocytes in the RA synovium in vivo. The destruction of cartilage due to synovial invasion was inhibited by ARG098 injection in the modified SCID-HuRAg mouse model. Conclusions ARG098 treatment suppressed RA synovial hyperplasia through the induction of apoptosis and prevented cartilage destruction in vivo. These results suggest that ARG098 might become a new therapy for RA.

  19. Association of β1 and β3 adrenergic receptors gene polymorphisms with insulin resistance and high lipid profiles related to type 2 diabetes and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Ana I. Burguete-García

    2014-06-01

    Full Text Available Background: Among the diverse genes associated to type 2 diabetes (T2D, the β-adrenergic receptors are an excellent candidate to study in Mexican population. The objective of this work was to analyze the association of polymorphisms in ADRB1 (rs1801253 (Arg389Gly and ADRB3 (Trp64Arg genes with T2D and metabolic syndrome (MS. Methods: We studied 445 MS patients, 502 with T2D and 552 healthy controls. Anthropometric features and complete biochemical profile were evaluated, and Arg389Gly and Trp64Arg SNPs were determined by TaqMan assays. Data analysis was adjusted by African, Caucasian and Amerindian ancestral percentage. Results: The variant Arg389Gly of ADRB1 was statistically associated with an increase of LDL levels (P < 0.008, and the variant ADRB3 Trp64Arg was associated to larger HOMA-IR (P < 0.018 and with an increase of insulin levels (P < 0.001. A multiple logistic regression analysis was made in three grouping models: For ADRB3 in the codominant model Trp/Arg genotype, there was an OR of 1.53 (1.09-2.13, P < 0.003 which was increased up to OR 2.99 (1.44-6.22, P < 0.003 for the Arg/Arg genotype. Similar risk association was found under the dominant model Trp/Arg-Arg/Arg genotype with OR 1.67 (1.21-2.30; P < 0.002. In the recessive model (Arg/Arg genotype, there was also a high association OR 2.56 (1.24-5.26, P < 0.01. Conclusions: The ADRB3 Trp64Arg variant is a susceptibility gene polymorphism for T2D and the ADRB1 Gly389Arg for lipid metabolism disruption. These results show that these variants are potential biomarkers for predicting metabolic alterations and evolution in diabetic and metabolic syndrome patients.

  20. A novel anti-virulence gene revealed by proteomic analysis in Shigella flexneri 2a

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    Ying Tianyi

    2010-06-01

    Full Text Available Abstract Background Shigella flexneri is a gram-negative, facultative pathogen that causes the majority of communicable bacterial dysenteries in developing countries. The virulence factors of S. flexneri have been shown to be produced at 37 degrees C but not at 30 degrees C. To discover potential, novel virulence-related proteins of S. flexneri, we performed differential in-gel electrophoresis (DIGE analysis to measure changes in the expression profile that are induced by a temperature increase. Results The ArgT protein was dramatically down-regulated at 37 degrees C. In contrast, the ArgT from the non-pathogenic E. coli did not show this differential expression as in S. flexneri, which suggested that argT might be a potential anti-virulence gene. Competitive invasion assays in HeLa cells and in BALB/c mice with argT mutants were performed, and the results indicated that the over-expression of ArgTY225D would attenuate the virulence of S. flexneri. A comparative proteomic analysis was subsequently performed to investigate the effects of ArgT in S. flexneri at the molecular level. We show that HtrA is differentially expressed among different derivative strains. Conclusion Gene argT is a novel anti-virulence gene that may interfere with the virulence of S. flexneri via the transport of specific amino acids or by affecting the expression of the virulence factor, HtrA.

  1. Antibiotic resistance genes occurrence and bacterial community composition in the Liuxi River

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    Wenguang eXiong

    2014-12-01

    Full Text Available Antibiotic resistance genes (ARGs in the environment have paid great concern due to their health risk. We investigated antibiotics concentrations (tetracyclines, sulfonamides and fluoroquinolones, ARGs abundances (tetracycline, sulfonamide and plasmid-mediated quinolone resistance (PMQR genes, and bacterial community composition in sediment and water samples in the Liuxi River, China. Antibiotics concentrations were determined by ultra-performance liquid chromatography-electrospray tandem mass spectrometry. ARGs abundances were quantified by a culture-independent method. Bacterial community composition was analyzed by metagenomic approach based on Ion Torrent Personal Genome Machine platform. Antibiotics concentrations were at the levels of 1.19 to 622 ug kg-1 in sediment samples and below the limit of detection to 127 ng L-1 in water samples. Relative abundances (ARGs copies/16S rRNA gene copies of detected ARGs were at the range of 10-5 to 10-2. The dominant phyla were Proteobacteria, Bacteroidetes and Verrucomicrobia in sediment samples, and were Proteobacteria, Actinobacteria and Bacteroidetes in water samples. The results indicated that the river environment was contaminated by antibiotics and may be as a reservoir of ARGs. This study provided quantitative data on antibiotics, ARGs and bacterial community composition in the Liuxi River, a geographical location different from the reported studies.

  2. Mechanism and Effect of Temperature on Variations in Antibiotic Resistance Genes during Anaerobic Digestion of Dairy Manure

    Science.gov (United States)

    Sun, Wei; Qian, Xun; Gu, Jie; Wang, Xiao-Juan; Duan, Man-Li

    2016-07-01

    Animal manure comprises an important reservoir for antibiotic resistance genes (ARGs), but the variation in ARGs during anaerobic digestion at various temperatures and its underlying mechanism remain unclear. Thus, we performed anaerobic digestion using dairy manure at three temperature levels (moderate: 20 °C, mesophilic: 35 °C, and thermophilic: 55 °C), to analyze the dynamics of ARGs and bacterial communities by quantitative PCR and 16S rRNA gene sequencing. We found that 8/10 detected ARGs declined and 5/10 decreased more than 1.0 log during thermophilic digestion, whereas only four and five ARGs decreased during moderate and mesophilic digestion, respectively. The changes in ARGs and bacterial communities were similar under the moderate and mesophilic treatments, but distinct from those in the thermophilic system. Potential pathogens such as Bacteroidetes, Proteobacteria, and Corynebacterium were removed by thermophilic digestion but not by moderate and mesophilic digestion. The bacterial community succession was the dominant mechanism that influenced the variation in ARGs and integrons during anaerobic digestion. Thermophilic digestion decreased the amount of mesophilic bacteria (Bacteroidetes and Proteobacteria) carrying ARGs. Anaerobic digestion generally decreased the abundance of integrons by eliminating the aerobic hosts of integrons (Actinomycetales and Bacilli). Thermophilic anaerobic digestion is recommended for the treatment and reuse of animal manure.

  3. Mechanism and Effect of Temperature on Variations in Antibiotic Resistance Genes during Anaerobic Digestion of Dairy Manure.

    Science.gov (United States)

    Sun, Wei; Qian, Xun; Gu, Jie; Wang, Xiao-Juan; Duan, Man-Li

    2016-07-22

    Animal manure comprises an important reservoir for antibiotic resistance genes (ARGs), but the variation in ARGs during anaerobic digestion at various temperatures and its underlying mechanism remain unclear. Thus, we performed anaerobic digestion using dairy manure at three temperature levels (moderate: 20 °C, mesophilic: 35 °C, and thermophilic: 55 °C), to analyze the dynamics of ARGs and bacterial communities by quantitative PCR and 16S rRNA gene sequencing. We found that 8/10 detected ARGs declined and 5/10 decreased more than 1.0 log during thermophilic digestion, whereas only four and five ARGs decreased during moderate and mesophilic digestion, respectively. The changes in ARGs and bacterial communities were similar under the moderate and mesophilic treatments, but distinct from those in the thermophilic system. Potential pathogens such as Bacteroidetes, Proteobacteria, and Corynebacterium were removed by thermophilic digestion but not by moderate and mesophilic digestion. The bacterial community succession was the dominant mechanism that influenced the variation in ARGs and integrons during anaerobic digestion. Thermophilic digestion decreased the amount of mesophilic bacteria (Bacteroidetes and Proteobacteria) carrying ARGs. Anaerobic digestion generally decreased the abundance of integrons by eliminating the aerobic hosts of integrons (Actinomycetales and Bacilli). Thermophilic anaerobic digestion is recommended for the treatment and reuse of animal manure.

  4. Effects of chlortetracycline and copper on tetracyclines and copper resistance genes and microbial community during swine manure anaerobic digestion.

    Science.gov (United States)

    Wang, Rui; Chen, Meixue; Feng, Feng; Zhang, Junya; Sui, Qianwen; Tong, Juan; Wei, Yuansong; Wei, Dongbin

    2017-08-01

    As antibiotic and heavy metals are over used in the livestock industry, animal manure is a reservoir of antibiotic resistance genes (ARGs). Anaerobic digestion has been reported to have the potential to reduce ARGs. However, few studies investigated whether reduction of ARGs would be affected by different external pressures including antibiotics and heavy metals during anaerobic digestion. The purpose of this study was thus to investigate effects of both chlortetracycline (CTC) and Cu on reduction of ARGs, heavy metal resistance genes (HMRGs) and mobile genetic elements (MGEs) during the swine manure anaerobic digestion. The results showed that the predominant ARGs (tetO, tetW, tetX, tetL) could be effectively reduced (approximately 1.00 log copies/g TS) through mesophilic anaerobic digestion. Microbial community evolution was the main driver. It was interesting that Treponema might indicate the termination of anaerobic digestion and compete with ARGs host bacteria. Addition of CTC, Cu and CTC+Cu affected microbial community change and hindered removal of ARGs, especially, CTC+Cu seriously affected Treponema and ARGs during anaerobic digestion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Antithrombotic Protective Effects of Arg-Pro-Gly-Pro Peptide during Emotional Stress Provoked by Forced Swimming Test in Rats.

    Science.gov (United States)

    Grigor'eva, M E; Lyapina, L A

    2017-01-01

    Blood coagulation was enhanced and all factors (total, enzyme, and non-enzyme) of the fibrinolytic system were suppressed in rats in 60 min after forced swimming test. Argininecontaining tetrapeptide glyproline Arg-Pro-Gly-Pro administered prior to this test activated fibrinolysis and prevented hypercoagulation. Administration of this peptide in 5 min after swimming test also enhanced anticoagulant, fibrinolytic, and antithrombotic activity of the blood. Therefore, glyproline Arg-Pro-Gly-Pro exerted both preventive and curative effects on the hemostasis system and prevented enhancement of blood coagulation provoked by emotional stress modeled by forced swimming test.

  6. Isolation of pyroGlu-Gly-Arg-Phe-NH2 (Antho-RFamide), a neuropeptide from sea anemones

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Ebbesen, Ditte Graff

    1986-01-01

    elegantissima. Three different methods established that the structure of the Anthopleura RFamide peptide (Antho-RFamide) is pyroGlu-Gly-Arg-Phe-NH2. Comparison of synthetic and natural Antho-RFamide and their enzymatic breakdown products on six different HPLC columns confirmed the structure of the sea anemone......A radioimmunoassay has been developed for peptides containing the carboxyl-terminal sequence Arg-Phe-NH2 (RFamide). Using this radioimmunoassay and applying cation-exchange chromatography and HPLC, we have isolated an RFamide peptide from acetic acid extracts of the sea anemone Anthopleura...

  7. As formações em bolas argênticas do sistema nervoso simpático

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    José Fernandez

    1957-09-01

    Full Text Available Foram estudados, histològicamente, gânglios simpáticos provenientes de 40 pacientes portadores de enfermidades variadas e 40 gânglios tidos como normais, para pesquisar as formações cm bolas argênticas. As impregnações foram feitas pelos métodos de Cajal, Arteta, Castro, Gros, Bielschowsky e Agduhr. Foi verificado que a presença de bolas argênticas é mais constante nas doenças circulatórias periféricas; nestas afecções, foi verificada, também, a presença de um pigmento corável pelos tricrômios de Gomori e de Goldner e que, possìvelmente, tem o mesmo significado que os descritos por Fedorow 12 corados pelo vermelho neutro; tais pigmentos foram relacionados com as formações em bolas argênticas, levando em consideração os trabalhos experimentais dos autores da escola russa. A presença das formações em bolas argênticas, tanto nos casos normais como nos patológicos, é atribuída a uma hiperfunção, por excitação, do simpático, por serem mais numerosas nos casos de transtornos periféricos. Foi observado que os neurônios em íntimo contacto com as formações em bolas argênticas, apresentam sempre alterações que vão desde o grau mais leve (tumefação do soma celular, retificação dos prolongamentos, neurofibrilas mais fortemente impregnadas, até o mais grave (hiperplasia e hipertrofia dos dendritos, degeneração retrátil, degeneração pigmentar. Foi notado que as terminações das fibras pré-ganglionares e as próprias fibras apresentam, muitas vêzes, alterações (hipertrofia, sinuosidade e grande poder de impregnação; as bolas argênticas foram observadas tanto no final dos dendritos como no das fibras pré-ganglionares. Foram encontradas formações de bolas argênticas em rosário, concluindo-se que elas têm a mesma significação que as alterações claviformes. Conclui-se, finalmente, que as bolas argênticas são produtos patológicos.

  8. Prevalence of sulfonamide and tetracycline resistance genes in drinking water treatment plants in the Yangtze River Delta, China.

    Science.gov (United States)

    Guo, Xueping; Li, Jing; Yang, Fan; Yang, Jie; Yin, Daqiang

    2014-09-15

    The occurrence and distribution of antibiotic resistance genes (ARGs) in drinking water treatment plants (DWTPs) and finished water are not well understood, and even less is known about the contribution of each treatment process to resistance gene reduction. The prevalence of ten commonly detected sulfonamide and tetracycline resistance genes, namely, sul I, sul II, tet(C), tet(G), tet(X), tet(A), tet(B), tet(O), tet(M) and tet(W) as well as 16S-rRNA genes, were surveyed in seven DWTPs in the Yangtze River Delta, China, with SYBR Green I-based real-time quantitative polymerase chain reaction. All of the investigated ARGs were detected in the source waters of the seven DWTPs, and sul I, sul II, tet(C) and tet(G) were the four most abundant ARGs. Total concentrations of ARGs belonging to either the sulfonamide or tetracycline resistance gene class were above 10(5) copies/mL. The effects of a treatment process on ARG removal varied depending on the overall treatment scheme of the DWTP. With combinations of the treatment procedures, however, the copy numbers of resistance genes were reduced effectively, but the proportions of ARGs to bacteria numbers increased in several cases. Among the treatment processes, the biological treatment tanks might serve as reservoirs of ARGs. ARGs were found in finished water of two plants, imposing a potential risk to human health. The results presented in this study not only provide information for the management of antibiotics and ARGs but also facilitate improvement of drinking water quality.

  9. The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

    Science.gov (United States)

    Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P.; Viana-Baptista, Miguel; Gomes, António Caldeira; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C.; Oliveira, João Paulo

    2015-01-01

    Summary Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue – GLA p.(Arg118Cys) –, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands’ close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease, since the allelic frequency in stroke patients was 0.0087 (p=0.0185 vs the general population). The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for “rare” condition. PMID:25468652

  10. A ergologia na Argélia The ergology in Algeria

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    Fyad Abderrahmane

    2011-01-01

    Full Text Available O depoimento revela aspectos das relações de trabalho, focalizando principalmente nos direitos do trabalho de proteção aos riscos e à saúde. Além disso, apresenta elementos históricos da colaboração entre professores-pesquisadores da Universidade de Oran, na Argélia, e professores-pesquisadores do Departamento de Ergologia da Universidade de Provence, na França, para a implementação de projetos e formação de médicos do trabalho.The testimony reveals aspects of labor relations, focusing primarily on labor rights protection and health risks. Maneover, it presents historical elements of collaboration between teachers and researchers at the Univesity of Oran, Algeria, and research faculty of the Departement of Ergology University of Provence, France for project implementation and training of occupational physicians.

  11. Arg-Phe-amide-like peptides in the primitive nervous systems of coelenterates

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Ebbesen, Ditte Graff

    1985-01-01

    By using immunocytochemistry and radioimmunoassays, several substances resembling vertebrate or invertebrate neuropeptides have been found in the nervous systems of coelenterates. The most abundant neuropeptides were those related to the molluscan neuropeptide Phe-Met-Arg-Phe-amide (FMRFamide). O...... with a RFamide antiserum and [J-125]-YFMRFamide as tracer, the RFamide-like peptide from sea anemones was isolated. After cation-exchange chromatography, gelfiltration and HPLC, this peptide was obtained in a pure form.......). Of antisera against different fragments of FMRFamide, those against RFamide were superior in recognizing the coelenterate peptide. Incubation of whole mounts with these RFamide antisera visualized the coelenterate nervous system in such a detail as has previously not been possible. By using a radioimmunoassay...

  12. Hemoglobin Willamette (β51Pro → Arg): Case Report and Literature Review

    Science.gov (United States)

    de Sousa Dias, Matheus Martins; Távora, Saymon Medeiros; de Galiza Neto, Gentil Claudino; de Souza, Jacqueline Holanda; da Silva, Herivaldo Ferreira

    2017-01-01

    We report a case of hemoglobin (Hb) Willamette (β51 Pro → Arg) in the Hematology Department of a tertiary hospital in Fortaleza, Northeast of Brazil. A literature review of the cases described in health sciences databases using as a descriptor Hb Willamette was performed, revealing 12 reported cases, of which only one presented with anemia. Herein, we describe a case of a female 29 years old, with hemoglobinopathy Willamette presenting clinically with anemia, having the lowest hemoglobin rate of the published cases. The relatives of the patient were evaluated andthe patient’s mother corresponded to the first description of the association between Hb Willamette and HbC. Among the hemoglobinopathies, hemoglobin Willamette is an extremely rare disease; therefore it is important to analyze its clinical and laboratory manifestations for accurate diagnosis and assessment of potential interactions with other genetic variants. PMID:28286631

  13. Hemoglobin Willamette (b51 Pro → Arg: case report and literature review

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    Orivaldo Alves Barbosa

    2017-03-01

    Full Text Available We report a case of hemoglobin (Hb Willamette (β51 Pro → Arg in the Hematology Department of a tertiary hospital in Fortaleza, Northeast of Brazil. A literature review of the cases described in health sciences databases using as a descriptor Hb Willamette was performed, revealing 12 reported cases, of which only one presented with anemia. Herein, we describe a case of a female 29 years old, with hemoglobinopathy Willamette presenting clinically with anemia, having the lowest hemoglobin rate of the published cases. The relatives of the patient were evaluated andthe patient’s mother corresponded to the first description of the association between Hb Willamette and HbC. Among the hemoglobinopathies, hemoglobin Willamette is an extremely rare disease; therefore it is important to analyze its clinical and laboratory manifestations for accurate diagnosis and assessment of potential interactions with other genetic variants.

  14. DIVERSITY OF THRIPS FAUNA (INSECTA: THYSANOPTERA IN PLUM ORCHARD FROM MORĂREŞTI-ARGES

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    Daniela Bărbuceanu

    2012-12-01

    Full Text Available The present study, conducted in the plums orchard of Morăreşti-Argeş at two plum varieties, has revealed a poor biodiversity. All of 10 species of thrips are polyphagous and belong to different trophic links: 8 species of phytophagous and 2 species, Aeolothrips intermedius and Haplothrips kurdjumovi are zoophagous. The structural parameters values indicate Haplothrips minutus as plum characteristic species, with the highest values of relative abundance and frequency in samples. However, this species has insignificant damaging in plum orchards. The low values of the structural indicators of the other species express their attachment to their characteristic trophic substratum, i.e. the herbaceous layer, so they only accidentally get on the plum branches, through anemochory. The Shannon-Weaver diversity index and equitability have low values, a situation which is typical of agro-ecosystems.

  15. Arg188 in rice sucrose transporter OsSUT1 is crucial for substrate transport

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    Sun Ye

    2012-11-01

    Full Text Available Abstract Background Plant sucrose uptake transporters (SUTs are H+/sucrose symporters related to the major facilitator superfamily (MFS. SUTs are essential for plant growth but little is known about their transport mechanism. Recent work identified several conserved, charged amino acids within transmembrane spans (TMS in SUTs that are essential for transport activity. Here we further evaluated the role of one of these positions, R188 in the fourth TMS of OsSUT1, a type II SUT. Results The OsSUT1(R188K mutant, studied by expression in plants, yeast, and Xenopus oocytes, did not transport sucrose but showed a H+ leak that was blocked by sucrose. The H+ leak was also blocked by β-phenyl glucoside which is not translocated by OsSUT1. Replacing the corresponding Arg in type I and type III SUTs, AtSUC1(R163K and LjSUT4(R169K, respectively, also resulted in loss of sucrose transport activity. Fluorination at the glucosyl 3 and 4 positions of α-phenyl glucoside greatly decreased transport by wild type OsSUT1 but did not affect the ability to block H+ leak in the R188K mutant. Conclusion OsSUT1 R188 appears to be essential for sucrose translocation but not for substrate interaction that blocks H+ leak. Therefore, we propose that an additional binding site functions in the initial recognition of substrates. The corresponding Arg in type I and III SUTs are equally important. We propose that R188 interacts with glucosyl 3-OH and 4-OH during translocation.

  16. Chemical rescue and inhibition studies to determine the role of Arg301 in phosphite dehydrogenase.

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    John E Hung

    Full Text Available Phosphite dehydrogenase (PTDH catalyzes the NAD(+-dependent oxidation of phosphite to phosphate. This reaction requires the deprotonation of a water nucleophile for attack on phosphite. A crystal structure was recently solved that identified Arg301 as a potential base given its proximity and orientation to the substrates and a water molecule within the active site. Mutants of this residue showed its importance for efficient catalysis, with about a 100-fold loss in k cat and substantially increased K m,phosphite for the Ala mutant (R301A. The 2.35 Å resolution crystal structure of the R301A mutant with NAD(+ bound shows that removal of the guanidine group renders the active site solvent exposed, suggesting the possibility of chemical rescue of activity. We show that the catalytic activity of this mutant is restored to near wild-type levels by the addition of exogenous guanidinium analogues; Brønsted analysis of the rates of chemical rescue suggests that protonation of the rescue reagent is complete in the transition state of the rate-limiting step. Kinetic isotope effects on the reaction in the presence of rescue agents show that hydride transfer remains at least partially rate-limiting, and inhibition experiments show that K i of sulfite with R301A is ∼400-fold increased compared to the parent enzyme, similar to the increase in K m for phosphite in this mutant. The results of our experiments indicate that Arg301 plays an important role in phosphite binding as well as catalysis, but that it is not likely to act as an active site base.

  17. Structural insights on mouse L-threonine dehydrogenase: A regulatory role of Arg180 in catalysis.

    Science.gov (United States)

    He, Chao; Huang, Xianyu; Liu, Yanhong; Li, Fudong; Yang, Yang; Tao, Hongru; Han, Chuanchun; Zhao, Chen; Xiao, Yazhong; Shi, Yunyu

    2015-12-01

    Mouse L-threonine dehydrogenase (mTDH), which belongs to the short-chain dehydrogenase/reductase (SDR) superfamily and mediates threonine catabolism, plays pivotal roles in both powerful biosynthesis and signaling in mouse stem cells and has a regulatory residue Arg180. Here we determined three crystal structures of mTDH: wild-type (WT) in the apo form; in complex with NAD(+) and a substrate analog, glycerol, or with only NAD(+); as well as the R180K variant with NAD(+). This is the first description of a structure for mammalian SDR-type TDH. Structural comparison revealed the structural basis for SDR-type TDH catalysis remains strictly conserved in bacteria and mammals. Kinetic enzyme assays, and isothermal titration calorimetry (ITC) measurements indicated the R180K mutation has little effect on NAD(+) binding affinity, whereas affects the substrate's affinity for the enzyme. The crystal structure of R180K with NAD(+), biochemical and spectroscopic studies suggested that the R180K mutant should bind NAD(+) in a similar way and have a similar folding to the WT. However, the R180K variant may have difficulty adopting the closed form due to reduced interaction of residue 180 with a loop which connects a key position for mTDH switching between the closed and open forms in mTDH catalysis, and thereby exhibited a significantly decreased kcat/Km value toward the substrate, L-Thr. In sum, our results suggest that activity of GalE-like TDH can be regulated by remote interaction, such as hydrogen bonding and hydrophobic interaction around the Arg180 of mTDH.

  18. Hyperactive Arg39Lys mutated mnemiopsin: implication of positively charged residue in chromophore binding cavity.

    Science.gov (United States)

    Mahdavi, Atiyeh; Sajedi, Reza H; Hosseinkhani, Saman; Taghdir, Majid

    2015-04-01

    Mnemiopsin, a Ca(2+)-regulated photoprotein isolated from Mnemiopsis leidyi, belongs to the family of ctenophore photoproteins. These proteins emit blue light from a chromophore, which is tightly but non-covalently bound in their central hydrophobic core that contains 21 conserved residues. In an effort to investigate the role of Arg39 (the sole charged residue in coelenterazine binding cavity of ctenophore photoproteins) in bioluminescence properties of these photoproteins, three mutated forms of mnemiopsin 1 (R39E, R39K and R39M) were constructed and characterized. The results indicate that while the luminescence activity of R39K mutated mnemiopsin has increased about nine fold compared to the wild type, R39M and R39E mutated mnemiopsins have entirely lost their activities. The most distinguished properties of R39K mutated photoprotein are its high activity, slow rate of luminescence decay and broad pH profile compared to the wild type. The complete loss of bioluminescence activity in mutated photoproteins with negatively charged and aliphatic residues (R39E and R39M, respectively) shows that the presence of a positively charged residue at this position is necessary. The results of spectroscopic studies, including CD, intrinsic and extrinsic fluorescence measurements and acrylamide quenching studies show that, while the substitutions lead to structural rigidity in R39E and R39M mutated mnemiopsins, structural flexibility is obvious in R39K mutated mnemiopsin. The presence of a more localized positive charge on ε-amino group of Lys compared to guanidinium group of Arg residue in close proximity to the choromophre might affect its fixation in the binding cavity and result in increased bioluminescence activity in this mutated photoprotein. It appears that the polarity and flexibility of positively charged residue at this position finely tunes the luminescence properties of ctenophore photoproteins.

  19. ARG (juegos de realidad alternativa. Contribuciones, limitaciones y potencialidades para la docencia universitaria

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    Teresa Piñeiro Otero

    2015-01-01

    Full Text Available La ludificación de la educación ha representado una oportunidad para fomentar la interacción, la motivación y la participación del alumnado. Los ARG (las siglas inglesas de juegos de realidad alternativa ofrecen una nueva herramienta altamente inmersiva que puede implementarse en el logro de los objetivos docentes. Uno de sus puntos fuertes consiste en la suma de esfuerzos y recursos (la llamada inteligencia colectiva aplicada a la resolución de problemas. A esto se añade su combinación de plataformas en los entornos online y offline, lo que favorece el «realismo» de la experiencia. En este sentido, el presente trabajo pretende condensar las potencialidades, limitaciones y retos de los ARG al servicio de la educación universitaria. Basándose, a nivel metodológico, en la elaboración de un corpus teórico relevante y adecuado, analiza el potencial educativo de esta herramienta que, en ámbitos como el marketing o la comunicación corporativa ya ha despegado con éxito, pero que en el área educativa todavía no había sido abordada en profundidad. Recopila, además, ejemplos satisfactorios que se han desarrollado en diversas disciplinas académicas en otros países y que no resultan fácilmente localizables. Se concluye que, dados los antecedentes, potencialidades y análisis expuesto, debe valorarse la posibilidad de incorporar los juegos de realidad alternativa a la práctica de la docencia universitaria en el marco de una estrategia educativa que determine sus objetivos y sistema de evaluación más adecuado.

  20. The chimeric peptide [Lys(-2)-Arg(-1)]-sarafotoxin-S6b, composed of the endothelin pro-sequence and sarafotoxin, retains the salt-bridge staple between Arg(-1) and Asp8 previously observed in [Lys(-2)-Arg(-1)]-endothelin. Implications of this salt-bridge in the contractile activity and the oxidative folding reaction.

    Science.gov (United States)

    Aumelas, A; Chiche, L; Kubo, S; Chino, N; Watanabe, T X; Kobayashi, Y

    1999-12-01

    The chimeric peptide [Lys(-2)-Arg(-1)]-sarafotoxin-S6b (KR-SRTb) designed from the Lys-2-Arg-1 dipeptide of the endothelin pro-sequence and the sarafotoxin-S6b sequence was synthesized. Its contractile activity was found to be decreased markedly when compared with that of the parent SRTb. In contrast, the extension by the Lys-Arg dipeptide was found to increase the formation of the native disulfide isomer (82/18 versus 96/4) when the reaction was carried out in the presence of redox reagents. The solution structure of KR-SRTb was determined by NMR as a function of pH. In the carboxylic acid state, the structure consists of the cystine-stabilized alpha-helical motif, with the alpha-helical part spanning residues 9-15, and of an unstructured C-terminal tail. In the carboxylate state, the structure is characterized by a salt-bridge between Arg(-1) and Asp8, which we identified previously in the [Lys(-2)-Arg(-1)]-endothelin-1 peptide (KR-ET-1). The fact that this salt-bridge is commonly observed in KR-SRTb and KR-ET-1, despite the 33% sequence difference between the corresponding parental peptides, highlights the remarkable adaptability of the Lys-Arg extension for the formation of a special salt-bridge. As a consequence, this salt-bridge, which does not depend on either the 4-7 sequence of the loop or the C-terminal sequence, appears to be particularly well suited to improve the stability of the cystine-stabilized alpha-helical motif. Therefore, because of its high yield in the native disulfide arrangement and its high permissiveness for sequence mutation in the 4-7 loop, such a stabilized cystine-stabilized alpha-helical motif could be a valuable scaffold for the presentation of a library of constrained short peptides.

  1. Occurrence of antibiotics and antibiotic resistance genes in a sewage treatment plant and its effluent-receiving river.

    Science.gov (United States)

    Xu, Jian; Xu, Yan; Wang, Hongmei; Guo, Changsheng; Qiu, Huiyun; He, Yan; Zhang, Yuan; Li, Xiaochen; Meng, Wei

    2015-01-01

    The extensive use of antibiotics has caused the contamination of both antibiotics and antibiotic resistance genes (ARGs) in the environment. In this study, the abundance and distribution of antibiotics and ARGs from a sewage treatment plant (STP) and its effluent-receiving river in Beijing China were characterized. Three classes of antibiotics including tetracycline, sulfonamide and quinolone were quantified by LC-MS/MS. In the secondary effluent they were detected at 195, 2001 and 3866 ng L(-1), respectively, which were higher than in the receiving river water. A total of 13 ARGs (6 tet genes: tetA, tetB, tetE, tetW, tetM and tetZ, 3 sulfonamide genes: sul1, sul2 and sul3, and 4 quinolone genes: gryA, parC, qnrC and qnrD) were determined by quantitative PCR. For all ARGs, sulfonamide resistance genes were present at relatively high concentrations in all samples, with the highest ARG concentration above 10(-1). ARGs remained relatively stable along each sewage treatment process. The abundances of detected ARGs from the STP were also higher than its receiving river. Bivariate correlation analysis showed that relative tet gene copies (tetB/16S-rRNA and tetW/16S-rRNA) were strongly correlated with the concentrations of tetracycline residues (r(2)>0.8, presistance gene (qnrC/16S-rRNA) and the concentrations of enrofloxacin (ENR) was also determined. The difference of ARGs levels in the raw influent and secondary effluent suggested that the STP treatment process may induce to increase the abundance of resistance genes. The results showed that the sewage was an important repository of the resistance genes, which need to be effectively treated before discharge into the natural water body.

  2. Occurrence of antimicrobials and antimicrobial resistance genes in beef cattle storage ponds and swine treatment lagoons

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuping; Zhang, Chiqian [Department of Civil Engineering, University of Nebraska-Lincoln, Lincoln, NE (United States); Parker, David B. [USDA Meat Animal Research Center, Clay Center, NE (United States); Snow, Daniel D. [Water Sciences Laboratory, University of Nebraska-Lincoln, Lincoln, NE (United States); Zhou, Zhi [Department of Civil and Environmental Engineering, National University of Singapore (Singapore); Li, Xu, E-mail: xuli@unl.edu [Department of Civil Engineering, University of Nebraska-Lincoln, Lincoln, NE (United States)

    2013-10-01

    Livestock manure treatment and storage structures are potential environmental sources of antimicrobials and antimicrobial resistance genes (ARGs). In this study, the occurrence of antimicrobials and ARGs was investigated in the water and the sludge compartments of beef cattle storage ponds and swine lagoons. Analysis was focused on two families of antimicrobials (sulfonamide and tetracycline) and the corresponding ARGs (sul1, sul2, tetO, tetQ and tetX). Results showed that the pseudo-partitioning coefficients of tetracyclines were higher than those of sulfonamides, suggesting different distributions of these two classes of antimicrobials between water and sludge. The ARGs tested were detected in nearly all ponds and lagoons, with the highest relative abundance in sul2 at 6.3 × 10{sup −1} copies per 16S rRNA gene. A positive correlation was observed between total sul genes and total sulfonamides in water while the correlation was negative in sludge. No significant correlation was found between total tet genes and total tetracyclines in either water or sludge, but significant correlations were observed for certain individual tet genes. Ammonia concentrations strongly correlated with all ARGs except tetX. This study provided quantitative information on the occurrence of antimicrobials and ARGs in the liquid and solid compartments of typical manure treatment and storage structures. - Highlights: • Partitioning of antimicrobials between water and sludge is compound specific. • Antimicrobial resistance genes occurred in both water and sludge. • The ARG abundance varied more substantially in swine lagoons than in cattle ponds. • Correlations between ARGs and antimicrobials are system dependent.

  3. Effects of manure and mineral fertilization strategies on soil antibiotic resistance gene levels and microbial community in a paddy-upland rotation system.

    Science.gov (United States)

    Lin, Hui; Sun, Wanchun; Zhang, Zulin; Chapman, Stephen J; Freitag, Thomas E; Fu, Jianrong; Zhang, Xin; Ma, Junwei

    2016-04-01

    This work investigated the responses of antibiotic resistance genes (ARGs) and the soil microbial community in a paddy-upland rotation system to mineral fertilizer (NPK) and different application dosages of manure combined with NPK. The occurrence of five tetracycline ARGs (tetA, tetB, tetC, tetG and tetW), two sulfonamide ARGs (sul1 and sul2) and one genetic element (IntI1) was quantified. NPK application showed only slight or no impact on soil ARGs abundances compared with the control without fertilizer. Soil ARGs abundances could be increased by manure-NPK application but was related to manure dosage (2250-9000 kg ha(-1)). Principal component analysis (PCA) showed that the soil ARG profile of the treatment with 9000 kg ha(-1) manure separated clearly from the other treatments; the ARGs that contributed most to the discrimination of this treatment were tetA, tetG, tetW, sul1, sul2 and IntI1. Community level physiological profile (CLPP) analysis showed that increasing manure dosage from 4500 kg ha(-1) to 9000 kg ha(-1) induced a sharp increase in almost all of the detected ARGs but would not change the microbial community at large. However, 9000 kg ha(-1) manure application produced a decline in soil microbial activity. Determination of antibiotics and heavy metals in soils suggested that the observed bloom of soil ARGs might associate closely with the accumulation of copper and zinc in soil.

  4. H2O2 and/or TiO2 photocatalysis under UV irradiation for the removal of antibiotic resistant bacteria and their antibiotic resistance genes.

    Science.gov (United States)

    Guo, Changsheng; Wang, Kai; Hou, Song; Wan, Li; Lv, Jiapei; Zhang, Yuan; Qu, Xiaodong; Chen, Shuyi; Xu, Jian

    2017-02-05

    Inactivating antibiotic resistant bacteria (ARB) and removing antibiotic resistance genes (ARGs) are very important to prevent their spread into the environment. Previous efforts have been taken to eliminate ARB and ARGs from aqueous solution and sludges, however, few satisfying results have been obtained. This study investigated whether photocatalysis by TiO2 was able to reduce the two ARGs, mecA and ampC, within the host ARB, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, respectively. The addition of H2O2 and matrix effect on the removal of ARB and ARGs were also studied. TiO2 thin films showed great effect on both ARB inactivation and ARGs removal. Approximately 4.5-5.0 and 5.5-5.8 log ARB reductions were achieved by TiO2 under 6 and 12mJ/cm(2) UV254 fluence dose, respectively. For ARGs, 5.8 log mecA reduction and 4.7 log ampC reduction were achieved under 120mJ/cm(2) UV254 fluence dose in the presence of TiO2. Increasing dosage of H2O2 enhanced the removal efficiencies of ARB and ARGs. The results also demonstrated that photocatalysis by TiO2 was capable of removing both intracellular and extracellular forms of ARGs. This study provided a potential alternative method for the removal of ARB and ARGs from aqueous solution.

  5. Association of Toll-like receptor 2 Arg753Gln and Toll-like receptor 1 Ile602Ser single-nucleotide polymorphisms with leptospirosis in an Argentine population.

    Science.gov (United States)

    Cédola, Maia; Chiani, Yosena; Pretre, Gabriela; Alberdi, Lucrecia; Vanasco, Bibiana; Gómez, Ricardo M

    2015-06-01

    Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an important role in the recognition of and subsequent immune response activation against leptospirosis in humans. The genetic polymorphism in TLR2 of an arginine to glutamine substitution at residue 753 (Arg753Gln) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to Leptospira spp. This bacterium signals through TLR2/TLR1 heterodimers in human cells. The aim of the present study was to investigate the Arg753Gln single-nucleotide polymorphism (SNP) of the TLR2 gene, and the isoleucine to serine transversion at position 602 (Ile602Ser) of the TLR1 gene (previously associated with Lyme disease), in leptospirosis patients compared to healthy controls, carrying out a retrospective case/control study. The TLR2 polymorphism adenine (A) allele was observed in 7.3% of leptospirosis patients but was not found in the control group, whereas the guanine (G) allele of the TLR1 polymorphism was found in 63.6% of patients and 41.6% of controls. Susceptibility to leptospirosis disease was increased 10.57-fold for carriers of the TLR2 G/A genotype (P=0.0493) and 3.85-fold for carriers of the TLR1 G/G genotype (P=0.0428). Furthermore, the risk of developing hepatic insufficiency and jaundice was increased 18.86- and 27.60-fold for TLR2 G/A carriers, respectively. Similarly, the risk of developing jaundice was increased 12.67-fold for TLR1 G allele carriers (G/G and T/G genotypes). In conclusion, the present data suggest that the TLR2 Arg753Gln and TLR1 Ile602Ser SNPs influence the risk of developing leptospirosis and its severity.

  6. Zona Incerta: o ARG como meio de construção colaborativa de conteúdo

    Directory of Open Access Journals (Sweden)

    Gabriel Costa Correia

    2011-05-01

    Full Text Available O presente artigo discorrerá sobre um estudo de caso realizado sobre o Alternate Reality Game (ARG Zona Incerta, realizado por membros da equipe da revista Superinteressante, publicação da Editora Abril, como estratégia de marketing alternativa para o produto Guaraná Antarctica, da empresa de bebidas AMBEV.

  7. Arg9 facilitates the translocation and downstream signal inhibition of an anti-HER2 single chain antibody

    Directory of Open Access Journals (Sweden)

    Hu Yi

    2012-07-01

    Full Text Available Abstract Background HER2 plays a critical role in the pathogenesis of many cancers and is linked to poor prognosis or cancer metastases. Monoclonal antibodies, such as Herceptin against HER2-overexpressing cancers, have showed satisfactory clinical therapeutic effect. However, they have difficulty to surmount obstacles to enter cells or blood–brain barrier. Results In this study, a cell-penetrating peptide Arg9 was linked to the C-terminus of anti-HER2 single chain antibody (MIL5scFv. Flow cytometry, confocal microscopy and electron microscopy analysis all revealed that Arg9 peptide facilitated the penetration of MIL5scFv into HER2-negative cell line NIH3T3 and orientate in mitochondria. More interestingly, Western blot assay showed the potential enhanced bioactivity of MIL5scFv-Arg9 in HER2+ cell line SKOV3, indicating that Arg9 could help large molecules (e.g. antibody to penetrate into cells and therefore enhance its anti-neoplastic function. Conclusions Our work represented an attractive by preliminary strategy to enhance the therapeutic effect of existing antibodies by entering cells easier, or more desirable, surmounting the physical barriers, especially in hard-to-reach cancers such as brain metastases cases.

  8. Functional assignment of Glu386 and Arg388 in the active site of l-galactono-¿-lactone dehydrogenase

    NARCIS (Netherlands)

    Leferink, N.G.H.; Jose, M.D.F.; Berg, van den W.A.M.; Berkel, van W.J.H.

    2009-01-01

    The flavoenzyme l-galactono-¿-lactone dehydrogenase (GALDH) catalyzes the terminal step of vitamin C biosynthesis in plants. Little is known about the catalytic mechanism of GALDH and related aldonolactone oxidoreductases. Here we identified an essential Glu–Arg pair in the active site of GALDH from

  9. ArgR and AhrC are both required for regulation of arginine metabolism in Lactococcus lactis

    NARCIS (Netherlands)

    Larsen, R; Buist, G; Kuipers, OP; Kok, J

    2004-01-01

    The DNA binding proteins ArgR and AhrC are essential for regulation of arginine metabolism in Escherichia Coli and Bacillus subtilis, respectively. A unique property of these regulators is that they form hexameric protein complexes, mediating repression of arginine biosynthetic pathways as well as a

  10. Influence of Soil Characteristics and Proximity to Antarctic Research Stations on Abundance of Antibiotic Resistance Genes in Soils.

    Science.gov (United States)

    Wang, Fang; Stedtfeld, Robert D; Kim, Ok-Sun; Chai, Benli; Yang, Luxi; Stedtfeld, Tiffany M; Hong, Soon Gyu; Kim, Dockyu; Lim, Hyoun Soo; Hashsham, Syed A; Tiedje, James M; Sul, Woo Jun

    2016-12-06

    Soil is an important environmental reservoir of antibiotic resistance genes (ARGs), which are increasingly recognized as environmental contaminants. Methods to assess the risks associated with the acquisition or transfer of resistance mechanisms are still underdeveloped. Quantification of background levels of antibiotic resistance genes and what alters those is a first step in understanding our environmental resistome. Toward this goal, 62 samples were collected over 3 years from soils near the 30-year old Gondwana Research Station and for 4 years before and during development of the new Jang Bogo Research Station, both at Terra Nova Bay in Antarctica. These sites reflect limited and more extensive human impact, respectively. A qPCR array with 384 primer sets targeting antibiotic resistance genes and mobile genetic elements (MGEs) was used to detect and quantify these genes. A total of 73 ARGs and MGEs encompassing eight major antibiotic resistance gene categories were detected, but most at very low levels. Antarctic soil appeared to be a common reservoir for seven ARGs since they were present in most samples (42%-88%). If the seven widespread genes were removed, there was a correlation between the relative abundance of MGEs and ARGs, more typical of contaminated sites. There was a relationship between ARG content and distance from both research stations, with a significant effect at the Jang Bogo Station especially when excluding the seven widespread genes; however, the relative abundance of ARGs did not increase over the 4 year period. Silt, clay, total organic carbon, and SiO2 were the top edaphic factors that correlated with ARG abundance. Overall, this study identifies that human activity and certain soil characteristics correlate with antibiotic resistance genes in these oligotrophic Antarctic soils and provides a baseline of ARGs and MGEs for future comparisons.

  11. Tet and sul antibiotic resistance genes in livestock lagoons of various operation type, configuration, and antibiotic occurrence

    Science.gov (United States)

    McKinney, C.W.; Loftin, K.A.; Meyer, M.T.; Davis, J.G.; Pruden, A.

    2010-01-01

    Although livestock operations are known to harbor elevated levels of antibiotic resistant bacteria, few studies have examined the potential of livestock waste lagoons to reduce antibiotic resistance genes (ARGs). The purpose of this study was to determine the prevalence and examine the behavior of tetracycline [tet(O) and tet(W)] and sulfonamide [sul(I) and su/(II)] ARGsin a broad cross-section of livestock lagoons within the same semiarid western watershed. ARGs were monitored for one year in the water and the settled solids of eight lagoon systems by quantitative polymerase chain reaction. In addition, antibiotic residues and various bulk water quality constituents were analyzed. It was found that the lagoons of the chicken layer operation had the lowest concentrations of both tet and sul ARGs and low total antibiotic concentrations, whereas su ARGs were highest in the swine lagoons, which generally corresponded to the highest total antibiotic concentrations. A marginal benefit of organic and small dairy operations also was observed compared to conventional and large dairies, respectively. In all lagoons, su ARGs were observed to be generally more recalcitrant than tet ARGs. Also, positive correlations of various bulk water quality constituents were identified with tet ARGs but not sul ARGs. Significant positive correlations were identified between several metals and tet ARGs, but Pearson's correlation coefficients were mostly lower than those determined between antibiotic residues and ARGs. This study represents a quantitative characterization of ARGs in lagoons across a variety of livestock operations and provides insight into potential options for managing antibiotic resistance emanating from agricultural activities. ?? 2010 American Chemical Society.

  12. High constitutive activity of a virus-encoded seven transmembrane receptor in the absence of the conserved DRY motif (Asp-Arg-Tyr) in transmembrane helix 3

    DEFF Research Database (Denmark)

    Rosenkilde, Mette M; Kledal, Thomas N; Schwartz, Thue W

    2005-01-01

    The highly conserved Arg in the so-called DRY motif (Asp-Arg-Tyr) at the intracellular end of transmembrane helix 3 is in general considered as an essential residue for G protein coupling in rhodopsin-like seven transmembrane (7TM) receptors. In the open reading frame 74 (ORF74) receptor encoded ...

  13. The association between changes in synovial fluid levels of ARGS-aggrecan fragments, progression of radiographic osteoarthritis and self-reported outcomes: a cohort study

    DEFF Research Database (Denmark)

    Larsson, S; Englund, M; Struglics, A;

    2012-01-01

    OBJECTIVE: To investigate whether change in concentrations over time of aggrecanase generated ARGS-aggrecan in synovial fluid (SF ARGS) associates with progression of radiographic knee osteoarthritis (OA) and patient-reported outcome in subjects with previous meniscectomy. METHODS: We studied 141...

  14. Lys-[Leu8,des-Arg9]-bradykinin blocks lipopolysaccharide-induced SHR aorta hyperpolarization by inhibition of Ca(++)- and ATP-dependent K+ channels.

    Science.gov (United States)

    Farias, Nelson C; Feres, Teresa; Paiva, Antonio C M; Paiva, Therezinha B

    2004-09-13

    The mediators involved in the hyperpolarizing effects of lipopolysaccharide and of the bradykinin B1 receptor agonist des-Arg9-bradykinin on the rat aorta were investigated by comparing the responses of aortic rings of spontaneously hypertensive and normotensive Wistar rats. Endothelized rings from hypertensive rats were hyperpolarized by des-Arg9-bradykinin and lipopolysaccharide, whereas de-endothelized rings responded to lipopolysaccharide but not to des-Arg9-bradykinin. In endothelized preparations, the responses to des-Arg9-bradykinin were inhibited by Nomega-nitro-L-arginine and iberiotoxin. De-endothelized ring responses to lipopolysaccharide were inhibited by iberiotoxin, glibenclamide and B1 antagonist Lys-[Leu8,des-Arg9]-bradykinin. This antagonist also inhibited hyperpolarization by des-Arg9-bradykinin and by the á2-adrenoceptor agonist, brimonidine. Our results indicate that Ca(2+)-sensitive K+ channels are the final mediators of the responses to des-Arg9-bradykinin, whereas both Ca(2+)- and ATP-sensitive K+ channels mediate the responses to lipopolysaccharide. The inhibitory effects of Lys-[Leu8,des-Arg9]-bradykinin is due to a direct action on Ca(2+)- and ATP-sensitive potassium channels.

  15. Isolation of the neuropeptide less than Glu-Trp-Leu-Lys-Gly-Arg-Phe-NH2 (Pol-RFamide II) from the hydromedusa Polyorchis penicillatus

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Rinehart, K L; Spencer, A N

    1992-01-01

    Using a radioimmunoassay for the sequence Arg-Phe-NH2 (RFamide), we have isolated the peptide less than Glu-Trp-Leu-Lys-Gly-Arg-Phe-NH2 (Pol-RFamide II) from acetic acid extracts of the hydromedusa Polyorchis penicillatus. This peptide is a neuropeptide and constitutes a peptide family together w...

  16. Dual receptor-targeting ⁹⁹mTc-labeled Arg-Gly-Asp-conjugated Alpha-Melanocyte stimulating hormone hybrid peptides for human melanoma imaging.

    Science.gov (United States)

    Xu, Jingli; Yang, Jianquan; Miao, Yubin

    2015-04-01

    The aim of this study was to examine whether the substitution of the Lys linker with the aminooctanoic acid (Aoc) and polyethylene glycol (PEG) linker could substantially decrease the non-specific renal uptake of (99m)Tc-labeled Arg-Gly-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) hybrid peptides. The RGD motif {Arg-Gly-Asp-DTyr-Asp} was coupled to [Cys(3,4,10), D-Phe(7), Arg(11)]α-MSH₃₋₁₃ via the Aoc or PEG₂ linker to generate RGD-Aoc-(Arg(11))CCMSH and RGD-PEG-(Arg(11))CCMSH. The biodistribution results of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH were examined in M21 human melanoma-xenografted nude mice. The substitution of Lys linker with Aoc and PEG₂ linker significantly reduced the renal uptake of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH by 58% and 63% at 2h post-injection. The renal uptake of (99m)Tc-RGD-Aoc-(Arg(11))CCMSH and (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH was 27.93 ± 3.98 and 22.01 ± 9.89% ID/g at 2 h post-injection. (99m)Tc-RGD-Aoc-(Arg(11))CCMSH displayed higher tumor uptake than (99m)Tc-RGD-PEG₂-(Arg(11))CCMSH (2.35 ± 0.12 vs. 1.71 ± 0.25% ID/g at 2 h post-injection). The M21 human melanoma lesions could be clearly visualized by SPECT/CT using (99m)Tc-RGD-Aoc-(Arg(11))CCMSH as an imaging probe. The favorable effect of Aoc and PEG₂ linker in reducing the renal uptake provided a new insight into the design of novel dual receptor-targeting radiolabeled peptides. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Investigation of KIF6 Trp719Arg in a case-control study of myocardial infarction: a Costa Rican population.

    Directory of Open Access Journals (Sweden)

    Lance A Bare

    Full Text Available BACKGROUND AND METHODOLOGY: The 719Arg allele of KIF6 (rs20455 was associated with coronary events in Caucasian participants of five prospective studies. We investigated whether this KIF6 variant was associated with non-fatal myocardial infarction (MI in a case-control study of an admixed population from the Central Valley of Costa Rica. Genotypes of the KIF6 variant were determined for 4,134 men and women. Cases (1,987 had survived a first MI; controls (2,147 had no history of MI and were matched to cases by age, sex, and area of residence. We tested the association between the KIF6 719Arg allele and non-fatal MI by conditional logistic regression and adjusted for admixture of founder populations. PRINCIPAL FINDINGS: Compared with the reference Trp/Trp homozygotes, KIF6 719Arg carriers were not at significantly higher risk for non-fatal MI in this study after adjustment for traditional risk factors or admixture (OR= 1.12; 95%CI, 0.98-1.28. Heterozygotes of the KIF6 Trp719Arg variant were at increased risk of non-fatal MI: the adjusted odds ratio was 1.16 (95% confidence interval, 1.01-1.34, but this association would not be significant after a multiple testing correction. CONCLUSIONS/SIGNIFICANCE: We found that carriers of the KIF6 719Arg allele were not at increased risk of non-fatal MI in a case-control study of Costa Ricans living in the Central Valley of Costa Rica.

  18. Analysis of local structure of Arg10 domain in apo-α- lactalbumin with a polarity-sensitive arginine-specific fluorescent probe

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    The polarity-sensitive fluorescent probe, 3-(4-chloro-6-p-glyoxalphenoxy-1,3,5-triazinylamino)-7- (dimethylamino)-2-methylphenazine, was used to analyze the local structure of apo-α-lactalbumin by detecting the polarity and conformational changes of the arginine residue (Arg10) domain. The polarity of the Arg10 domain in both native and heat-denatured apo-α-lactalbumin was determined, which corresponds to a dielectric constant of 16, and the hydrophobic core near the Arg10 was found to be conservative for heating. Meanwhile, the effect of Ca2+ binding on the conformational changes of the Arg10 domain was studied, revealing that the hydrophobic core near the Arg10 is insensitive to the binding of Ca2+.

  19. Association of the beta3-adrenergic receptor Trp64Arg polymorphism with common metabolic traits: studies of 7605 middle-aged white people

    DEFF Research Database (Denmark)

    Gjesing, A. P.; Andersen, G; Borch-Johnsen, K;

    2008-01-01

    of type 2 diabetes and obesity in a relatively large, homogenous study population. METHODS: The Trp64Arg polymorphism was genotyped in 7605 Danish subjects using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Association was examined in case-control studies of obesity (1529...... cases and 6049 controls) and type 2 diabetes (1373 cases and 4742 controls) and quantitative trait analyses among 5822 individuals. Furthermore, the association of Trp64Arg with type 2 diabetes was examined in a meta-analysis. RESULTS: The Trp64Arg polymorphism was not associated with obesity. However...... (p=0.02). After sex stratification these associations were only present among women. Furthermore, the Arg-allele was borderline associated with type 2 diabetes in a meta-analysis of the present and 26 previous studies (p=0.06, OR1.27 (CI: 0.99-1.63)) (n=18891). CONCLUSION/INTERPRETATION: Trp64Arg...

  20. Technetium-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptides for human melanoma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yang Jianquan; Guo Haixun [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Miao Yubin, E-mail: ymiao@salud.unm.ed [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Dermatology, University of New Mexico, Albuquerque, NM 87131 (United States)

    2010-11-15

    Introduction: The purpose of this study was to examine whether {sup 99m}Tc-labeled Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone ({alpha}-MSH) hybrid peptide targeting both melanocortin-1 (MC1) and {alpha}{sub v{beta}3} integrin receptors was superior in melanoma targeting to {sup 99m}Tc-labeled {alpha}-MSH or RGD peptide targeting only the MC1 or {alpha}{sub v{beta}3} integrin receptor. Methods: RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were designed to target both MC1 and {alpha}{sub v{beta}3} integrin receptors, MC1 receptor only and {alpha}{sub v{beta}3} integrin receptor only, respectively. The MC1 or {alpha}{sub v{beta}3} integrin receptor binding affinities of three peptides were determined in M21 human melanoma cells. The melanoma targeting properties of {sup 99m}Tc-labeled RGD-Lys-(Arg{sup 11})CCMSH, RAD-Lys-(Arg{sup 11})CCMSH and RGD-Lys-(Arg{sup 11})CCMSHscramble were determined in M21 human melanoma-xenografted nude mice. Meanwhile, the melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was blocked with various non-radiolabeled peptides in M21 melanoma xenografts. Results: RGD-Lys-(Arg{sup 11})CCMSH displayed 2.0 and 403 nM binding affinities to both MC1 and {alpha}{sub v{beta}3} integrin receptors, whereas RAD-Lys-(Arg{sup 11})CCMSH or RGD-Lys-(Arg{sup 11})CCMSHscramble lost their {alpha}{sub v{beta}3} integrin receptor binding affinity by greater than 248-fold or MC1 receptor binding affinity by more than 100-fold, respectively. The melanoma uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH was 2.49 and 2.24 times (P < .05) the melanoma uptakes of {sup 99m}Tc-RAD-Lys-(Arg{sup 11})CCMSH and {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSHscramble at 2 h post-injection, respectively. Either RGD or (Arg{sup 11})CCMSH peptide co-injection could block 42% and 57% of the tumor uptake of {sup 99m}Tc-RGD-Lys-(Arg{sup 11})CCMSH, whereas the coinjection of RGD+(Arg{sup 11})CCMSH peptide mixture

  1. Effects of thermophilic composting on oxytetracycline, sulfamethazine, and their corresponding resistance genes in swine manure.

    Science.gov (United States)

    Wang, Jian; Ben, Weiwei; Zhang, Yu; Yang, Min; Qiang, Zhimin

    2015-09-01

    Environmental contamination caused by residual antibiotics and antibiotic resistance genes (ARGs) in concentrated animal feeding operations has drawn increasing attention. This study investigated the removal of oxytetracycline (OTC) and sulfamethazine (SMN) as well as the behavior of their corresponding ARGs through a series of simulated composting tests with swine manure. The results indicate that the composting piles became fully mature after 32 days when the thermophilic stage was maintained at 55 °C for 3.5 days. At an initial spiked concentration of 50 (SMN) and 32 mg kg(-1) (OTC), their removal efficiency could reach 89.8% and 100%, respectively. An abiotic process was mainly responsible for the degradation of SMN, whereas both abiotic and biotic processes were responsible for the degradation of OTC. Among all the studied ARGs, only the tetracycline resistance genes (TRGs) encoding ribosomal protection proteins remained relatively stable throughout the composting process, while those encoding efflux pump (EFP) and enzymatic inactivation (EI) proteins and sulfonamide resistance genes (SRGs) obviously increased when the composting was complete. The addition of antibiotics inhibited the microbial activity in the early stage of composting but promoted the proliferation of ARGs particularly in the mesophilic stage. Integron-mediated horizontal gene transfers played an important role in the proliferation of most ARG types studied (i.e., EFP TRGs, EI TRG and SRGs). In summary, thermophilic composting of swine manure could remove the studied antibiotics effectively, but failed to prevent the proliferation of their corresponding ARGs.

  2. Dietary L-arginine supplementation differentially regulates expression of lipid-metabolic genes in porcine adipose tissue and skeletal muscle.

    Science.gov (United States)

    Tan, Bie; Yin, Yulong; Liu, Zhiqiang; Tang, Wenjie; Xu, Haijun; Kong, Xiangfeng; Li, Xinguo; Yao, Kang; Gu, Wanting; Smith, Stephen B; Wu, Guoyao

    2011-05-01

    Obesity is a major health crisis worldwide and new treatments are needed to fight this epidemic. Using the swine model, we recently reported that dietary L-arginine (Arg) supplementation promotes muscle gain and reduces body-fat accretion. The present study tested the hypothesis that Arg regulates expression of key genes involved in lipid metabolism in skeletal muscle and white adipose tissue. Sixteen 110-day-old barrows were fed for 60 days a corn- and soybean-meal-based diet supplemented with 1.0% Arg or 2.05% L-alanine (isonitrogenous control). Blood samples, longissimus dorsi muscle and overlying subcutaneous adipose tissue were obtained from 170-day-old pigs for biochemical studies. Serum concentrations of leptin, alanine and glutamine were lower, but those for Arg and proline were higher in Arg-supplemented pigs than in control pigs. The percentage of oleic acid was higher but that of stearic acid and linoleic acid was lower in muscle of Arg-supplemented pigs, compared with control pigs. Dietary Arg supplementation increased mRNA levels for fatty acid synthase in muscle, while decreasing those for lipoprotein lipase, glucose transporter-4, and acetyl-coenzyme A carboxylase-α in adipose tissue. Additionally, mRNA levels for hormone sensitive lipase were higher in adipose tissue of Arg-supplemented pigs compared with control pigs. These results indicate that Arg differentially regulates expression of fat-metabolic genes in skeletal muscle and white adipose tissue, therefore favoring lipogenesis in muscle but lipolysis in adipose tissue. Our novel findings provide a biochemical basis for explaining the beneficial effect of Arg in improving the metabolic profile in mammals (including obese humans). Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Temporal changes of antibiotic-resistance genes and bacterial communities in two contrasting soils treated with cattle manure.

    Science.gov (United States)

    Hu, Hang-Wei; Han, Xue-Mei; Shi, Xiu-Zhen; Wang, Jun-Tao; Han, Li-Li; Chen, Deli; He, Ji-Zheng

    2016-02-01

    The emerging environmental spread of antibiotic-resistance genes (ARGs) and their subsequent acquisition by clinically relevant microorganisms is a major threat to public health. Animal manure has been recognized as an important reservoir of ARGs; however, the dissemination of manure-derived ARGs and the impacts of manure application on the soil resistome remain obscure. Here, we conducted a microcosm study to assess the temporal succession of total bacteria and a broad spectrum of ARGs in two contrasting soils following manure application from cattle that had not been treated with antibiotics. High-capacity quantitative PCR detected 52 unique ARGs across all the samples, with β-lactamase as the most dominant ARG type. Several genes of soil indigenous bacteria conferring resistance to β-lactam, which could not be detected in manure, were found to be highly enriched in manure-treated soils, and the level of enrichment was maintained over the entire course of 140 days. The enriched β-lactam resistance genes had significantly positive relationships with the relative abundance of the integrase intI1 gene, suggesting an increasing mobility potential in manure-treated soils. The changes in ARG patterns were accompanied by a significant effect of cattle manure on the total bacterial community compositions. Our study indicates that even in the absence of selective pressure imposed by agricultural use of antibiotics, manure application could still strongly impact the abundance, diversity and mobility potential of a broad spectrum of soil ARGs. Our findings are important for reliable prediction of ARG behaviors in soil environment and development of appropriate strategies to minimize their dissemination.

  4. Exploring Antibiotic Resistance Genes and Metal Resistance Genes in Plasmid Metagenomes from Wastewater Treatment Plants

    Directory of Open Access Journals (Sweden)

    An-Dong eLi

    2015-09-01

    Full Text Available Plasmids operate as independent genetic elements in microorganism communities. Through horizontal gene transfer, they can provide their host microorganisms with important functions such as antibiotic resistance and heavy metal resistance. In this study, six metagenomic libraries were constructed with plasmid DNA extracted from influent, activated sludge and digested sludge of two wastewater treatment plants. Compared with the metagenomes of the total DNA extracted from the same sectors of the wastewater treatment plant, the plasmid metagenomes had significantly higher annotation rates, indicating that the functional genes on plasmids are commonly shared by those studied microorganisms. Meanwhile, the plasmid metagenomes also encoded many more genes related to defense mechanisms, including ARGs. Searching against an antibiotic resistance genes (ARGs database and a metal resistance genes (MRGs database revealed a broad-spectrum of antibiotic (323 out of a total 618 subtypes and metal resistance genes (23 out of a total 23 types on these plasmid metagenomes. The influent plasmid metagenomes contained many more resistance genes (both ARGs and MRGs than the activated sludge and the digested sludge metagenomes. Sixteen novel plasmids with a complete circular structure that carried these resistance genes were assembled from the plasmid metagenomes. The results of this study demonstrated that the plasmids in wastewater treatment plants could be important reservoirs for resistance genes, and may play a significant role in the horizontal transfer of these genes.

  5. Sulphonamide and trimethoprim resistance genes persist in sediments at Baltic Sea aquaculture farms but are not detected in the surrounding environment.

    Directory of Open Access Journals (Sweden)

    Windi Indra Muziasari

    Full Text Available Persistence and dispersal of antibiotic resistance genes (ARGs are important factors for assessing ARG risk in aquaculture environments. Here, we quantitatively detected ARGs for sulphonamides (sul1 and sul2 and trimethoprim (dfrA1 and an integrase gene for a class 1 integron (intI1 at aquaculture facilities in the northern Baltic Sea, Finland. The ARGs persisted in sediments below fish farms at very low antibiotic concentrations during the 6-year observation period from 2006 to 2012. Although the ARGs persisted in the farm sediments, they were less prevalent in the surrounding sediments. The copy numbers between the sul1 and intI1 genes were significantly correlated suggesting that class 1 integrons may play a role in the prevalence of sul1 in the farm sediments through horizontal gene transfer. In conclusion, the presence of ARGs may limit the effectiveness of antibiotics in treating fish illnesses, thereby causing a potential risk to the aquaculture industry. However, the restricted presence of ARGs at the farms is unlikely to cause serious effects in the northern Baltic Sea sediment environments around the farms.

  6. Monitoring and evaluation of the water quality of Budeasa Reservoir-Arges River, Romania.

    Science.gov (United States)

    Ion, Antoanela; Vladescu, Luminita; Badea, Irinel Adriana; Comanescu, Laura

    2016-09-01

    The purpose of this study was to monitor and record the specific characteristics and properties of the Arges River water in the Budeasa Reservoir (the principal water resources of municipal tap water of the big Romanian city Pitesti and surrounding area) for a period of 5 years (2005-2009). The monitored physical and chemical parameters were turbidity, pH, electrical conductivity, chemical oxygen demand, 5 days biochemical oxygen demand, free dissolved oxygen, nitrite, nitrate, ammonia nitrogen, chloride, total dissolved iron ions, sulfate, manganese, phosphate, total alkalinity, and total hardness. The results were discussed in correlation with the precipitation values during the study. Monthly and annual values of each parameter determined in the period January 2005-December 2009 were used as a basis for the classification of Budeasa Reservoir water, according to the European legislation, as well as for assessing its quality as a drinking water supply. Principal component analysis and Pearson correlation coefficients were used as statistical procedures in order to evaluate the data obtained during this study.

  7. Effects of Arg26 and Lys27 mutation on the bioactivity of HNTX-Ⅳ

    Institute of Scientific and Technical Information of China (English)

    XIONG Xia; XU Xia; LI Dongling; CHEN Ping; LIANG Songping

    2007-01-01

    Hainantoxin-Ⅳ (HNTX-Ⅳ)was isolated from the Chinese bird spider Ornithoctorcs hainana and identified as a novel antagonist of tetrodotoxin-sensitive (TTX-S)sodium channels.As revealed by the solution structure of HNTX-Ⅳ solved by two-dimensional nuclear magnetic resonance (2D-NMR),HNTX-Ⅳ adopts an inhibitor cystine knot motif.To check the role of basic residues during HNTX-Ⅳ's interaction with TTX-S sodium channels,R26A and K27A mutants of HNTX-Ⅳ were constructed by solid-phase chemical synthesis.The synthesized peptides were purified and refolded under optimized oxidation conditions.Correct synthesis and folding were confirmed by MALDI-TOF mass spectrometry and NMR spectroscopy,respectively.Using the whole-cell patch-clamp technique,Lys27 but not Arg26 was identified as a key residue for HNTX-Ⅳ's bioactivity against TTX-S sodium channels,because R26A-HNTX-Ⅳ showed slightly reduced activity and K27A-HNTX-Ⅳ showed almost no inhibition.

  8. The effect of climate on populations of grape moths in the vineyard Stefanesti-Arges

    Directory of Open Access Journals (Sweden)

    Daniela BĂRBUCEANU

    2005-05-01

    Full Text Available In the period 1998-2003, in the vineyard Stefanesti-Arges, observing was carried out, with the help of pheromone traps, of the population of grape moths, Eupoecilia ambiguella Hb. and Lobesia botrana Den et Schiff. The different climatic preferences of both species, establish that, in accordance with the yearly conditions, one of the two species is dominated by the other. The year 1998 is the only year when the percentages of captures of the two species are nearly: 57% - L. botrana and 42,89% - E. ambiguella, while in 1999 is the only year when E. ambiguella dominated in number the species L. botrana - 66,28%. For meeting this situation it needed two years of consecutives optimum climate for the activity of species E. ambiguella (like the year 1998 and 1999. In the period 2000-2003, the species Lobesia botrana was dominated by E. ambiguella, but as a result of very raised temperatures of summers of years 2000, 2002 and 2003, the population of L. botrana diminished very much and there was no need for fighting back treatments.

  9. Analgesic and Anti-Inflammatory Activities of Leaf Extract of Mallotus repandus (Willd. Muell. Arg.

    Directory of Open Access Journals (Sweden)

    Md. Mahadi Hasan

    2014-01-01

    Full Text Available In folk medicine Mallotus repandus (Willd. Muell. Arg. is used to treat muscle pain, itching, fever, rheumatic arthritis, snake bite, hepatitis, and liver cirrhosis. This study aimed to evaluate the antinociceptive as well as the anti-inflammatory activities of the methanol extract of leaf. The leaves were extracted with methanol following hot extraction and tested for the presence of phytochemical constituents. Analgesic and anti-inflammatory activities were evaluated using acetic acid induced writhing test, xylene induced ear edema, cotton pellet induced granuloma, and tail immersion methods at doses of 500, 1000, and 2000 mg/kg body weight. The presence of flavonoids, saponins, and tannins was identified in the extract. The extract exhibited considerable antinociceptive and anti-inflammatory activities against four classical models of pain. In acetic acid induced writhing, xylene induced ear edema, and cotton pellet granuloma models, the extract revealed dose dependent activity. Additionally, it increased latency time in tail immersion model. It can be concluded that M. repandus possesses significant antinociceptive potential. These findings suggest that this plant can be used as a potential source of new antinociceptive and anti-inflammatory candidates. The activity of methanol extract is most likely mediated through central and peripheral inhibitory mechanisms. This study justified the traditional use of leaf part of this plant.

  10. Anatomia da madeira de Phyllanthus sellowianus Müll. Arg. (Phyllanthaceae

    Directory of Open Access Journals (Sweden)

    Luciano Denardi

    2013-01-01

    Full Text Available The present study aimed to describe the wood anatomy of Phyllanthus sellowianus Müll. Arg.(Phyllanthaceae, as well as the research of anatomical characters associated with the flexibility of their stems, desirable characteristic for bioengineering works. Belonging to the group of reophyllous and with up to three meters in height, the species occurs naturally in the south of Brazil, Uruguay and Argentina. The exsicat and wood sample from a P. sellowianus, located in the municipality of Santa Maria, Rio Grande do Sul state, Brazi, were deposited in the University Federal de Santa Maria under the numbers HDCF 5587 e 5588. Standard technique was used to set the histological lamina of wood. For macerations used the method of Jeffrey. The Wood anatomy description followed the IAWA Committee (1989. The microscopic analysis revealed the presence vassels of small diameter (< 60µm, radial multiples of 2 to 4 units, and simple perforation plates, obliquely, axial parenchyma absent, heterogeneous rays, with 1-3 cells large, and gelatinous fibers. The absence of axial parenchyma and laticifer tubes is compatible to the Phyllanthaceae group. The presence of perforated ray cells is, probably, the main anatomic component for differentiation of P. sellowianus from the other species of the genera. The abundant presence of gelatinous fibers certainly is one of the main anatomical characteristics related to the high flexibility of its stem.

  11. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Yi-Yong; Lee, Dong-Keon [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); So, Ju-Hoon; Kim, Cheol-Hee [Department of Biology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Jeoung, Dooil [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Lee, Hansoo [Department of Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Choe, Jongseon [Department of Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Won, Moo-Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Ha, Kwon-Soo [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Kwon, Young-Guen [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-752 (Korea, Republic of); Kim, Young-Myeong, E-mail: ymkim@kangwon.ac.kr [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of)

    2015-08-07

    Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC{sub 50} of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases.

  12. 纤维蛋白原γ链Arg275His突变所致的遗传性异常纤维蛋白原血症家系分析%Analysis of a family with congenital dysfibrinogenemia caused by an Arg275His mutation in the gamma chain of fibrinogen

    Institute of Scientific and Technical Information of China (English)

    闫婕; 邓东红; 邓雪连; 罗美玲; 程鹏; 廖林; 林发全

    2016-01-01

    Objective To explore the clinical phenotype of a family affected with congenital dysfibrinogenemia and potential mutations underlying the disease.Methods Coagulation testing and hepatorenal function testing were conducted on 18 individuals fromthree generations.Plasma fibrinogen was extracted and analyzed with SDS-PAGE electrophoresis.All of the exons and flanking sequences of fibrinogen FGA,FGB,FGG genes were analyzed by PCR,and the products were subjected to Sanger sequencing.Results Hepatorenal function,prothrombin time and activated partial thromboplastin time of the proband were all normal.However,his thrombin time was significantly prolonged.Fibrinogen activity was decreased,while the concentration of antigen was in the normal range.The results of his mother,brother,and nephew were similar.DNA sequencing has confirmed that the proband,his mother,brother,and nephew have all carried a g.5877G> A mutation in the exon 8 of the FGG gene,which resultedin replacement of arginine (Arg) by histidine (His) at position 275.Conclusion The Arg275His mutation of the fibrinogen γ chain probably underlies the pathogenesis of congenital dysfibrinogenemia in this family.%目的 对1个遗传性异常纤维蛋白原血症家系进行临床表型和基因型研究,了解其分子遗传学发病机制.方法 抽取家系18名成员外周血,进行凝血指标检测;提取血浆纤维蛋白原,进行SDS-PAGE电泳;PCR扩增纤维蛋白原FGA、FGB、FGG基因所有外显子以及侧翼序列.PCR扩增产物进行测序,确定突变位点.结果 先证者肝肾功能、凝血酶原时间与活化部分凝血活酶时间均正常,但凝血酶时间显著延长.纤维蛋白原活性明显降低,而抗原浓度在正常范围,先证者母亲、弟弟及侄子的表型检测结果与其相似.基因测序结果显示,先证者及其母亲、弟弟及侄子FGG基因第8外显子发生了g.5877G>A杂合突变,导致275位的精氨酸(Arg)被组氨酸(His)取代.FGG基因第8

  13. Development and adaptation of the ELBIS Elbe river information system into a water quality information system of the ARGE-ELBE working group. Final report; Entwicklung und Anpassung des Elbeinformationssystems ELBIS fuer ein Gewaessergueteinformationssystem der ARGE-ELBE. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Frank, B.; Prange, A.

    2001-07-01

    The geo-information system ELBIS was installed in mid-November 2000 to provide information on the web on Elbe water quality and other information. It presents the current results of the national Elbe monitoring programme of the ARGE Elbe working group, as well as the results of the 'Elbe 2000' programme of the nineties. [German] Das Geo-Informationssystem ELBIS informiert seit November 2000 im Internet ueber die Wasserqualitaet und verwandte Elbe-Themen. Mittels einer geografischen Oberflaeche stellt es die fortlaufenden, aktuellen Ergebnisse der nationalen Elbe-Messprogramme der ARGE Elbe (Arbeitsgemeinschaft fuer die Reinhaltung der Elbe) dar sowie Forschungsdaten aus der 'Elbe 2000'-Schadstoffforschung der neunziger Jahre. Auf einfache und zeitgemaesse Weise macht ELBIS diese Ergebnisse der interessierten Oeffentlichkeit zugaenglich und bietet Fachleuten einen umfassenden Ueberblick ueber die Datenlage. (orig.)

  14. Development and adaptation of the ELBIS Elbe river information system into a water quality information system of the ARGE-ELBE working group. Final report; Entwicklung und Anpassung des Elbeinformationssystems ELBIS fuer ein Gewaessergueteinformationssystem der ARGE-ELBE. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Frank, B.; Prange, A.

    2001-07-01

    The geo-information system ELBIS was installed in mid-November 2000 to provide information on the web on Elbe water quality and other information. It presents the current results of the national Elbe monitoring programme of the ARGE Elbe working group, as well as the results of the 'Elbe 2000' programme of the nineties. [German] Das Geo-Informationssystem ELBIS informiert seit November 2000 im Internet ueber die Wasserqualitaet und verwandte Elbe-Themen. Mittels einer geografischen Oberflaeche stellt es die fortlaufenden, aktuellen Ergebnisse der nationalen Elbe-Messprogramme der ARGE Elbe (Arbeitsgemeinschaft fuer die Reinhaltung der Elbe) dar sowie Forschungsdaten aus der 'Elbe 2000'-Schadstoffforschung der neunziger Jahre. Auf einfache und zeitgemaesse Weise macht ELBIS diese Ergebnisse der interessierten Oeffentlichkeit zugaenglich und bietet Fachleuten einen umfassenden Ueberblick ueber die Datenlage. (orig.)

  15. A Comprehensive Analysis on Spread and Distribution Characteristic of Antibiotic Resistance Genes in Livestock Farms of Southeastern China.

    Directory of Open Access Journals (Sweden)

    Na Wang

    Full Text Available The pollution of antibiotic resistance genes (ARGs in livestock farms is a problem which need to be paid more attention to, due to the severe resistance dissemination and the further human health risk. In this study, all the relevant exposure matrices (manure, soil and water of sixteen animal farms in Southeastern China were sampled to determine twenty-two ARGs conferring resistance to five major classes of antibiotics including tetracyclines, sulfonamides, quinolones, aminoglycosides, and macrolides. The results showed that the spread property of sul genes was most extensive and strong, followed by tet and erm genes. The abundance of tet genes expressing ribosomal protection proteins (tetM, tetO, tetQ, tetT and tetW was higher than that expressing efflux pump proteins (tetA, tetC, tetE and tetG in each type of samples. The high abundance and frequency of ermB gene in the matrices should be paid more attention, because macrolides is a major medicine for human use. For manures, it was found that the similar ARGs distribution rules were existing in poultry manure or porcine manure samples, despite of the different origins of these two types of livestock farms. Meanwhile, it was interesting that the distribution rule of tet genes in animal manure was nearly the same as all the ARGs. For soils, the result of nonmetric multi-dimensional scaling (NMDS analysis showed that the pollution of ARGs in the soils fertilized by poultry and cattle manures were more substantial in northern Jiangsu, but no significant ARGs diversity was observed among porcine manured soils of five different regions. Furthermore, most ARGs showed significant positive relationships with environmental variables such as concentration of sulfonamides, tetracyclines, Cu, Zn and total organic carbon (TOC. The pollution profile and characteristics of so many ARGs in livestock farms can provide significative foundation for the regulation and legislation of antibiotics in China.

  16. Synthesis and electrochemical properties of ferrocene-peptides Boc-HN-Fca-Gly-Gly-Tyr-Arg-OMe%二茂铁-肽Boc-HN-Fca-Gly-Gly-Tyr-Arg-OMe的合成和电化学性质

    Institute of Scientific and Technical Information of China (English)

    王芳斌; 谭月敏; 刘又年; 曾冬铭; 向娟

    2007-01-01

    以二茂铁二甲酸、甘氨酸、酪氨酸和精氨酸为原料,通过多步反应,合成新的二茂铁-肽衍生物Boc-HN-Fca-Gly-Gly-Tyr-Arg-OMe(7)(Fca代表二茂铁氨基酸)和Boc-HN-Fca-Gly-Gly-Tyr-Arg-OH(8),对寡聚肽的合成进行研究;对合成产物进行红外光谱和氢核磁共振谱表征,并运用循环伏安(CV)方法对产物的电化学性能进行研究.研究结果表明:产物(7)和(8)的产率分别为83.5%和80.2%;Boc-HN-Fca-Gly-Gly-Tyr-Arg-OMe的循环伏安扫描结果是氧化峰和还原峰电位分别为0.385 V和0.346 V,峰电位之差△Ep为41 mV,峰电流密度之比Jpa/Jpc为1.055;对于Boc-HN-Fca-Gly-Gly-Tyr-Arg-OH,其氧化峰和还原峰电位分别为0.532 V和0.453 V,峰电位之差△Ep为79 mV,峰电流密度之比Jpa/Jpc为0.928.

  17. Exploring antibiotic resistance genes and metal resistance genes in plasmid metagenomes from wastewater treatment plants.

    Science.gov (United States)

    Li, An-Dong; Li, Li-Guan; Zhang, Tong

    2015-01-01

    Plasmids operate as independent genetic elements in microorganism communities. Through horizontal gene transfer (HGT), they can provide their host microorganisms with important functions such as antibiotic resistance and heavy metal resistance. In this study, six metagenomic libraries were constructed with plasmid DNA extracted from influent, activated sludge (AS) and digested sludge (DS) of two wastewater treatment plants (WWTPs). Compared with the metagenomes of the total DNA extracted from the same sectors of the wastewater treatment plant, the plasmid metagenomes had significantly higher annotation rates, indicating that the functional genes on plasmids are commonly shared by those studied microorganisms. Meanwhile, the plasmid metagenomes also encoded many more genes related to defense mechanisms, including ARGs. Searching against an antibiotic resistance genes (ARGs) database and a metal resistance genes (MRGs) database revealed a broad-spectrum of antibiotic (323 out of a total 618 subtypes) and MRGs (23 out of a total 23 types) on these plasmid metagenomes. The influent plasmid metagenomes contained many more resistance genes (both ARGs and MRGs) than the AS and the DS metagenomes. Sixteen novel plasmids with a complete circular structure that carried these resistance genes were assembled from the plasmid metagenomes. The results of this study demonstrated that the plasmids in WWTPs could be important reservoirs for resistance genes, and may play a significant role in the horizontal transfer of these genes.

  18. Sludge as a potential important source of antibiotic resistance genes in both the bacterial and bacteriophage fractions.

    Science.gov (United States)

    Calero-Cáceres, William; Melgarejo, Ana; Colomer-Lluch, Marta; Stoll, Claudia; Lucena, Francisco; Jofre, Juan; Muniesa, Maite

    2014-07-01

    The emergence and prevalence of antibiotic resistance genes (ARGs) in the environment is a serious global health concern. ARGs found in bacteria can become mobilized in bacteriophage particles in the environment. Sludge derived from secondary treatment in wastewater treatment plants (WWTPs) constitutes a concentrated pool of bacteria and phages that are removed during the treatment process. This study evaluates the prevalence of ARGs in the bacterial and phage fractions of anaerobic digested sludge; five ARGs (blaTEM, blaCTX-M, qnrA, qnrS, and sul1) are quantified by qPCR. Comparison between the wastewater and sludge revealed a shift in the prevalence of ARGs (blaTEM and sul1 became more prevalent in sludge), suggesting there is a change in the bacterial and phage populations from wastewater to those selected during the secondary treatment and the later anaerobic mesophilic digestion of the sludge. ARGs densities were higher in the bacterial than in the phage fraction, with high densities in both fractions; particularly for blaTEM and sul1 (5 and 8 log10 gene copies (GC)/g, respectively, in bacterial DNA; 5.5 and 4.4 log10 GC/g, respectively, in phage DNA). These results question the potential agricultural uses of treated sludge, as it could contribute to the spread of ARGs in the environment and have an impact on the bacterial communities of the receiving ecosystem.

  19. The role of Arg(78) in the metabotropic glutamate receptor mGlu(1) for agonist binding and selectivity

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Sheppard, P O; O'Hara, P J

    2000-01-01

    likely, through the formation of an ionic bond between its positively charged side chain and the distal acid group of the agonists. Furthermore, the different impact of the two mutations on (S)-glutamic acid and (S)-quisqualic acid potencies strongly indicates that while Arg(78) appears to be a common......The metabotropic glutamate receptors belong to family C of the G-protein coupled receptor superfamily. These receptors all possess large extracellular amino terminal domains, where agonist binding takes place. We have previously constructed a molecular model of the amino terminal domain of the m......Glu(1) receptor based on a weak amino acid sequence similarity with a family of bacterial periplasmic binding proteins (PBPs). The residues Ser(165) and Thr(188) were demonstrated to be involved in agonist binding to the receptor. Here, we report that mutation of Arg(78) in the mGlu(1b) receptor...

  20. Ecología, etnobotánica y etnofarmacología del argán (Argania spinosa)

    OpenAIRE

    López Sáez, José Antonio; Alba Sánchez, Francisca

    2009-01-01

    Argania spinosa es una especie leñosa endémica del suroeste de Marruecos que ha jugado un papel fundamental, desde un punto de vista etnobotánico, en la economía local de los pueblos bereberes. El aceite de argán se extrae de manera artesanal de los frutos de esta planta siguiendo un modelo etnográfico de gran interés. En el presente trabajo se sintetizan, mediante una profunda revisión bibliográfica, los conocimientos referidos a la ecología, etnobotánica y etnofarmacología del argán y se de...

  1. The Role of TP53 Gene Codon 72 Polymorphism in Leukemia: A PRISMA-Compliant Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Ruan, Xiao-Lan; Li, Sheng; Meng, Xiang-Yu; Geng, Peiliang; Gao, Qing-Ping; Ao, Xu-Bin

    2015-09-01

    The purpose of this meta-analysis was aimed to evaluate the association of tumor protein p53 (TP53) gene codon 72 polymorphism with leukemia susceptibility. We searched PubMed to identify relevant studies, and 16 case-control studies from 14 published articles were identified as eligible studies, including 2062 leukemia patients and 5826 controls. After extracting data, odds ratio (OR) with the corresponding 95% confidence interval (95%CI) was applied to assess the association between TP53 codon 72 polymorphism and leukemia susceptibility. The meta-analysis was performed with the Comprehensive Meta-Analysis software, version 2.2. Overall, no significant association between TP53 codon 72 polymorphism and leukemia susceptibility was found in this meta-analysis (Pro vs Arg: OR = 1.05, 95%CI = 0.90-1.21; Pro/Pro vs Arg/Arg: OR = 1.13, 95%CI = 0.84-1.52; Arg/Pro vs Arg/Arg: OR = 0.94, 95%CI = 0.76-1.15; [Pro/Pro + Arg/Pro] vs Arg/Arg: OR = 0.99, 95%CI = 0.80-1.21; Pro/Pro vs [Arg/Arg + Arg/Pro]: OR = 1.19, 95%CI = 0.93-1.51). Similar results were also found in subgroup analysis by ethnicity, source of controls, and types of leukemia (either acute myeloid leukemia or acute lymphocytic leukemia). Our meta-analysis demonstrates that TP53 codon 72 polymorphism may not be a risk factor for acute leukemia; however, due to the limitations of this study, it should be verified in future studies.

  2. Isolation of L-3-phenyllactyl-Leu-Arg-Asn-NH2 (Antho-RNamide), a sea anemone neuropeptide containing an unusual amino-terminal blocking group

    DEFF Research Database (Denmark)

    Grimmelikhuijzen, C J; Rinehart, K L; Jacob, E

    1990-01-01

    -phenyllactyl-Leu-Arg-Asn-NH2. By using reversed-phase HPLC and a chiral mobile phase, it was shown that the 3-phenyllactyl group had the L configuration. Immunocytochemical staining with antiserum against Arg-Asn-NH2 showed that L-3-phenyllactyl-Leu-Arg-Asn-NH2 (Antho-RNamide) was localized in neurons of sea...... anemones. The L-3-phenyllactyl group has not been found earlier in neuropeptides of vertebrates or higher invertebrates. We propose that this residue renders Antho-RNamide resistant to nonspecific aminopeptidases, thereby increasing the stability of the peptide after neuronal release....

  3. Inactivation of antibiotic resistance genes in municipal wastewater by chlorination, ultraviolet, and ozonation disinfection.

    Science.gov (United States)

    Zhuang, Yao; Ren, Hongqiang; Geng, Jinju; Zhang, Yingying; Zhang, Yan; Ding, Lili; Xu, Ke

    2015-05-01

    This study investigated the inactivation of two antibiotic resistance genes (ARGs)-sul1 and tetG, and the integrase gene of class 1 integrons-intI1 by chlorination, ultraviolet (UV), and ozonation disinfection. Inactivation of sul1, tetG, and intI1 underwent increased doses of three disinfectors, and chlorine disinfection achieved more inactivation of ARGs and intI1 genes (chlorine dose of 160 mg/L with contact time of 120 min for 2.98-3.24 log reductions of ARGs) than UV irradiation (UV dose of 12,477 mJ/cm(2) for 2.48-2.74 log reductions of ARGs) and ozonation disinfection (ozonation dose of 177.6 mg/L for 1.68-2.55 log reductions of ARGs). The 16S rDNA was more efficiently removed than ARGs by ozone disinfection. The relative abundance of selected genes (normalized to 16S rDNA) increased during ozonation and with low doses of UV and chlorine disinfection. Inactivation of sul1 and tetG showed strong positive correlations with the inactivation of intI1 genes (for sul1, R (2)  = 0.929 with p disinfection, ozonation disinfection, Fenton oxidation, and coagulation), chlorination is an alternative method to remove ARGs from wastewater effluents. At a chlorine dose of 40 mg/L with 60 min contact time, the selected genes inactivation efficiency could reach 1.65-2.28 log, and the cost was estimated at 0.041 yuan/m(3).

  4. Functional characterizations of residues Arg-158 and Tyr-170 of the mosquito-larvicidal Bacillus thuringiensis Cry4Ba

    Science.gov (United States)

    Leetachewa, Somphob; Moonsom, Saengduen; Chaisri, Urai; Khomkhum, Narumol; Yoonim, Nonglak; Wang, Ping; Angsuthanasombat, Chanan

    2014-01-01

    The insecticidal activity of Bacillus thuringiensis (Bt) Cry toxins involves toxin stabilization, oligomerization, passage across the peritrophic membrane (PM), binding to midgut receptors and pore-formation. The residues Arg-158 and Tyr-170 have been shown to be crucial for the toxicity of Bt Cry4Ba. We characterized the biological function of these residues. In mosquito larvae, the mutants R158A/E/Q (R158) could hardly penetrate the PM due to a significantly reduced ability to alter PM permeability; the mutant Y170A, however, could pass through the PM, but degraded in the space between the PM and the midgut epithelium. Further characterization by oligomerization demonstrated that Arg-158 mutants failed to form correctly sized high-molecular weight oligomers. This is the first report that Arg-158 plays a role in the formation of Cry4Ba oligomers, which are essential for toxin passage across the PM. Tyr-170, meanwhile, is involved in toxin stabilization in the toxic mechanism of Cry4Ba in mosquito larvae. [BMB Reports 2014; 47(10): 546-551] PMID:24286331

  5. Cyclo(L-Pro-D-Arg): a new antibacterial and antitumour diketopiperazine from Bacillus cereus associated with a rhabditid entomopathogenic.

    Science.gov (United States)

    Kumar, S Nishanth; Mohandas, C; Nambisan, Bala; Sreerag, R S; Jayaprakas, C A

    2014-05-01

    In continuation of our search for new antimicrobial secondary metabolites from Bacillus cereus associated with rhabditid entomopathogenic nematode, a new microbial diketopiperazine, cyclo(L-Pro-D-Arg), was isolated from the ethyl acetate extract of fermented modified nutrient broth. The chemical structures of the isolated compounds were identified based on their 1D, 2D NMR and high-resolution electrospray ionisation-mass spectroscopy data. Antibacterial activity of the compound was determined by minimum inhibitory concentration and disc diffusion method against medically important bacteria, and the compound was recorded to have significant antibacterial activity against test bacteria. The highest activity was recorded against Klebsiella pneumoniae (1 μg/mL). Cyclo(L-Pro-D-Arg) was recorded to have significant antitumor activity against HeLa cells (IC50 value 50 μg/mL), and this compound was recorded to have no cytotoxicity against normal monkey kidney cells (VERO) up to 100 μg/mL). To the best of our knowledge, this is the first time that cyclo(L-Pro-D-Arg) has been isolated from a microbial natural source.

  6. Pharmacobotanic characterization of young stems and stem barks of Rauvolfia sellowii Müll. Arg., Apocynaceae

    Directory of Open Access Journals (Sweden)

    Leopoldo Clemente Baratto

    2010-09-01

    Full Text Available Rauvolfia sellowii Müll. Arg. (Apocynaceae, a Brazilian native tree rich in indole alkaloids, is known as "pau-pra-tudo" and popularly used as hypocholesterolemic, hypoglycemic and antihypertensive. The aim of this work was to study the anatomy of the young stems and stem barks of this medicinal plant, in order to contribute to the identification of the species as a drug. The plant material was fixed and prepared according to standard microtechniques. The young stems have remaining epidermis, but a suberified peridermis is evident. The phellogen is located in the cortical region, forming suber externally. Underneath the phellogen, lies the phelloderm and collenchymatic region. In the cortex, there are numerous laticifers and some fibers. There is an incomplete sclerenchymatic sheath, consisting of several groups of fibers and stone cells. The stem has internal phloem ordered as isolated groups side by side. Numerous laticifers, calcium oxalate crystals, idioblasts and amyloplasts are found in the cortex, phloem, xylem and pith. The stem bark has many layers of suber and cortical parenchyma, a sheath composed of fibers and stone cells totally lignified, and external phloem. These anatomical characteristic, taken together, can be used as quality control parameters for this species.Rauvolfia sellowii Müll. Arg. (Apocynaceae, uma árvore nativa brasileira rica em alcaloides indólicos, é conhecida como "pau-pra-tudo" e utilizada popularmente como hipocolesterolêmica, hipoglicêmica e anti-hipertensiva. O presente trabalho teve como objetivo caracterizar anatomicamente o caule jovem e a casca caulinar dessa planta medicinal, a fim de contribuir para a identificação e autenticidade da droga. O material vegetal foi fixado e submetido às microtécnicas usuais. O caule jovem possui epiderme remanescente, porém uma periderme suberificada é observada. O felogênio instala-se na região cortical, formando súber externamente. Subjacentes ao felog

  7. Abundance of antibiotic resistance genes in environmental bacteriophages.

    Science.gov (United States)

    Anand, Taruna; Bera, Bidhan Ch; Vaid, Rajesh K; Barua, Sanjay; Riyesh, Thachamvally; Virmani, Nitin; Hussain, Mubarik; Singh, Raj K; Tripathi, Bhupendra N

    2016-12-01

    The ecosystem is continuously exposed to a wide variety of antimicrobials through waste effluents, agricultural run-offs and animal-related and anthropogenic activities, which contribute to the spread of antibiotic resistance genes (ARGs). The contamination of ecosystems with ARGs may create increased opportunities for their transfer to naive microbes and eventually lead to entry into the human food chain. Transduction is a significant mechanism of horizontal gene transfer in natural environments, which has traditionally been underestimated as compared to transformation. We explored the presence of ARGs in environmental bacteriophages in order to recognize their contribution in the spread of ARGs in environmental settings. Bacteriophages were isolated against environmental bacterial isolates, purified and bulk cultured. They were characterized, and detection of ARG and intI genes including blaTEM, blaOXA-2, intI1, intI2, intI3, tetA and tetW was carried out by PCR. This study revealed the presence of various genes [tetA (12.7 %), intI1 (10.9 %), intI2 (10.9 %), intI3 (9.1 %), tetW (9.1 %) and blaOXA-2 (3.6 %)] and blaTEM in a significantly higher proportion (30.9 %). blaSHV, blaOXA-1, tetO, tetB, tetG, tetM and tetS were not detected in any of the phages. Soil phages were the most versatile in terms of ARG carriage. Also, the relative abundance of tetA differed significantly vis-à-vis source. The phages from organized farms showed varied ARGs as compared to the unorganized sector, although blaTEM ARG incidences did not differ significantly. The study reflects on the role of phages in dissemination of ARGs in environmental reservoirs, which may provide an early warning system for future clinically relevant resistance mechanisms.

  8. meta Analysis of Effect of LEPR Gln223Arg Polymorphism on Breast Cancer Risk in Different Ethnic Populations%LEPR Gln223Arg多态性对不同种族人群中乳腺癌危险性影响的meta分析

    Institute of Scientific and Technical Information of China (English)

    许晔琼; 李瑞; 高天翼; 顾玲; 聂珍琳; 陈丽萍; 宋国齐; 王书奎

    2012-01-01

    瘦素和瘦素受体参与了乳腺癌的发生发展过程.在瘦素受体基因(LEPR)6号外显子上第223个密码子A到G的转变可以导致谷氨酸到精氨酸的替换(Gln223Arg).许多已发表的病例对照研究评价了LEPR Gln223Arg多态性与乳腺癌的关系.然而,却未得出一致的结论.本篇meta分析囊括了8篇文献来评价LEPR Gln223Arg多态性与乳腺癌的联系.用总体合并OR值作为研究共显性模型、隐性模型、显性模型的指标.结果显示总体研究中隐性模型(OR=1.32,95%CI:1.03~1.69)和Arg/Gln vs Gln/Gln基因型(OR=1.16,95%CI:1.01~1.34)显著提高了乳腺癌的危险性.种族分层分析中发现,非洲人群的以下几个基因型会提高患乳腺癌的危险性:Arg/Arg vs Gln/Gln (OR=1.86,95%CI:1.28~2.71),Arg/Gln vs Gln/Gln (OR=1.48,95%CI:1.10~1.99),显性模型(OR=1.60,95%CI:1.21~2.11)和隐性模型(OR=1.48,95%CI:1.07~2.05);亚洲人群中,Arg/Arg vs Gln/Gln基因型(OR=6.79,95%CI:3.42~13.47)和显性模型(OR=2.03,95%CI:1.42~2.90)提高了患乳腺癌的危险性.在欧洲人群中任何基因模型都没有发现能显著提高乳腺癌的危险性.总而言之,LEPR 223Arg是乳腺癌发展的低风险因素,特别是在非洲女性中.%Leptin and leptin receptor have been implicated in processes of breast cancer. An A to G transition of codon 223th in exon 6 of leptin receptor gene (LEPR) can result in the substitution from glutamine to arginine (Gln223Arg). A variety of case-control papers have been published to evaluate the association between LEPR Gln223Arg polymorphism and breast cancer. However, they have got contradictory conclusions. This meta analysis enrolls 8 papers to evaluate the connection of them. The pooled Ors are took for codominant model, recessive model, dominant model. The result shows that recessive model (OR=1.32, 95%CI: 1.03-1.69) and genotype Arg/Gln vs Gln/Gln (OR=1.16, 95%CI: 1.01-1.34) significantly improve breast cancer risk

  9. Laxative activities of Mareya micrantha (Benth. Müll. Arg. (Euphorbiaceae leaf aqueous extract in rats

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    Djaman Joseph A

    2010-02-01

    Full Text Available Abstract Background Mareya micrantha (Benth. Müll. Arg. (Euphorbiaceae is a shrub that is commonly used in Côte d'Ivoire (West Africa for the treatment of constipation and as an ocytocic drug. The present study was carried out to investigate the laxative activity of Mareya micrantha in albino's Wistar rats. Methods Rats were divided in 5 groups of 5 animals each, first group as control, second group served as standard (sodium picosulfate while group 3, 4 and 5 were treated with leaf aqueous extract of Mareya micrantha at doses of 100, 200 and 400 mg/kg body weight (b.w., per os respectively. The laxative activity was determined based on the weight of the faeces matter. The effects of the leaves aqueous extract of Mareya micrantha and castor oil were also evaluated on intestinal transit, intestinal fluid accumulation and ions secretion. Results Phytochemicals screening of the extract revealed the presence of flavonoids, alkaloids, tannins, polyphenols, sterols and polyterpenes. The aqueous extract of Mareya micrantha applied orally (100, 200 and 400 mg/kg; p.o., produced significant laxative activity and reduced loperamide induced constipation in dose dependant manner. The effect of the extract at 200 and 400 mg/kg (p.o. was similar to that of reference drug sodium picosulfate (5 mg/kg, p.o. The same doses of the extract (200 and 400 mg/kg, p.o. produced a significant increase (p -, Na+, K+ and Ca2+ in the intestinal fluid (p Conclusions The results showed that the aqueous extract of Mareya micrantha has a significant laxative activity and supports its traditional use in herbal medicine.

  10. In vivo andin vitro phytochemical and antibacterial efficacy ofBaliospermum montanum(Willd.)Muell.Arg

    Institute of Scientific and Technical Information of China (English)

    JohnsonM; WeselyEG; ZahirHussain MI; SelvanN

    2010-01-01

    Objective:To evaluate the phytochemical and anti-bacterial potential of mother plantsin vivo andin vitro derived callus ofBaliospermum montanum (B. montanum) (Willd.) Muell.-Arg. leaves and root.Methods:Thein vitro derived rootlets and leaves segments ofB. montanum were cut into0.5-0.7 cm in length and cultured on Murashige and Skoog solid medium supplemented with 3% sucrose, gelled with0.7% agar and different concentration of2, 4-Deither alone or in combinations. The preliminary phytochemical screening was performed by Harborne method. Antibacterial efficacy was performed by well diffusion method and incubated for24 h at37 ℃.Results:The highest percentage of callus formation (leaves segments86.9±0.56; root segments78.7±0.51) was obtained on Murashige and Skoog’s basal medium supplemented with 3% sucrose and2.0 mg/L of 2, 4-Dichlorophenoxy acetic acid. The phytochemical study revealed the high quantity presence of steroids, triterpenoids, glycosides, saponins, alkaloids, flavanoids, phenolic compounds, tannins, sugars etc of root and leaves derived calli. The ethanol extract of leaves segment derived calli ofB. montanum showed the maximum solubility and antimicrobial activity with the MIC ranged from 100to 200 μL.Conclusions: The preliminary phytochemical study confirmed that the calli mediated tissues showed the higher percentage of metabolite constituents and extraction value compared to thein vivo leaves and roots. The present study observation suggested that a possibility to establish high yielding genotypes byin vitro culture for production of medicinally important bioactive compounds.

  11. The Storage Stability of Anthocyanins in Mao (Antidesma thwaitesianum Müll. Arg. Juice and Concentrate

    Directory of Open Access Journals (Sweden)

    Prommakool Arunya

    2016-01-01

    Full Text Available Mao or Makmao (Antidesma thwaitesianum Müll. Arg. is a wild plant found in the northeast of Thailand. Mao is one of fruits which are source of anthocyanins. Mao fruits are used for juice and concentrate which are consumed for healthy drinks. Determination of the kinetic parameters is essential to predict the quality changes and stability of anthocyanins in Mao juice and concentrate that occur during storage. The purpose of this research was to study the degradation of anthocyanins in Mao juice and concentrate during storage at 5, 30 and 37°C for 15 days. The storage stability of Mao anthocyanins was studied in 15°Brix juice and 45°Brix concentrate. The degradation kinetic (k, half-life (t1/2, activation energy (Ea and Q10 values for Mao anthocyanins degradation were determined. The results indicated that analysis of kinetic data for the degradation of anthocyanins followed a first-order reaction. An increase storage temperature from 5 to 30 and 37°C increased k value of anthocyanins in Mao juice and concentrate. Increasing storage temperature decreased t1/2 value of anthocyanins in both concentrations. At 5, 30 and 37°C, the t1/2 of anthocyanins decreased from 35 to 13 and 5 days for Mao juice and 32 to 25 and 21 days for Mao concentrate. The Ea value of the anthocyanins degradation in Mao juice and concentrate were 38.03 and 8.42 kJ/mol, respectively. Q10 values of both Mao juice and concentrate at 30-37°C were higher than those were storaged at 5-30°C. Thus higher stability of anthocyanins was achieved by using concentration and storage at lower temperature.

  12. Recent trends in phytochemistry, ethnobotany and pharmacological significance of Alchornea cordifolia (Schumach. & Thonn.) Muell. Arg.

    Science.gov (United States)

    Boniface, Pone Kamdem; Ferreira, Sabrina Baptista; Kaiser, Carlos Roland

    2016-09-15

    Alchornea cordifolia (Schumach. & Thonn.) Muell. Arg. (Euphorbiaceae) (A. cordifolia) is widely distributed throughout tropical Africa, where it is used extensively in traditional medicine. Conditions for which the plant has enjoyed wide use are: coughs, gonorrhoea, infertility, prostatitis, bacterial infections, diarrhoea, ulcers, pain, inflammation, fever and bronchial troubles. This review summarizes the achievements of the investigations in traditional uses, ethnobotany, phytochemistry, biological activities and toxicological profile of A. cordifolia; this review also describes the shortcomings of studies on this herbal drug and thus serves as the basis of further scientific research and development of this traditional herbal drug. A. cordifolia-related information was collected from various resources including published articles in peer-reviewed journals, unpublished materials, textbooks, government survey reports and scientific databases such as Scifinder®, Pubmed, Science Direct, Wiley, Springer, ACS, Scielo, Web of Science and other web search instruments (Google, Yahoo), published on the subject from 1950 to 2016. 'The Plant List' (www.theplantlist.org) and 'Kew Royal Botanic Gardens' (mpns.kew.org) were used to validate the scientific name of the plant. The literature revealed several reports on traditional uses, biological activities, chemical constituents and toxicological evaluation of A. cordifolia. The phytochemical information indicates identification of 95 compounds including fatty acids, terpenoids, flavonoids, phenolic acids, alkaloids, which exhibited various pharmacological activities such as wound healing, anti-inflammation, anticancer, antioxidant, immunomodulation, antidiarrhoeal, antimicrobial, antidepressant, hepatoprotective, antiplasmodial and anxiolytic. However, there are still significant gaps in the completeness of our understanding of A. cordifolia bioactivity, therapeutic value, and roles played by each of the numerous

  13. N-Protonated Isomers and Coulombic Barriers to Dissociation of Doubly Protonated Ala8Arg

    Science.gov (United States)

    Haeffner, Fredrik; Irikura, Karl K.

    2017-10-01

    Collision-induced dissociation (or tandem mass spectrometry, MS/MS) of a protonated peptide results in a spectrum of fragment ions that is useful for inferring amino acid sequence. This is now commonplace and a foundation of proteomics. The underlying chemical and physical processes are believed to be those familiar from physical organic chemistry and chemical kinetics. However, first-principles predictions remain intractable because of the conflicting necessities for high accuracy (to achieve qualitatively correct kinetics) and computational speed (to compensate for the high cost of reliable calculations on such large molecules). To make progress, shortcuts are needed. Inspired by the popular mobile proton model, we have previously proposed a simplified theoretical model in which the gas-phase fragmentation pattern of protonated peptides reflects the relative stabilities of N-protonated isomers, thus avoiding the need for transition-state information. For singly protonated Ala n ( n = 3-11), the resulting predictions were in qualitative agreement with the results from low-energy MS/MS experiments. Here, the comparison is extended to a model tryptic peptide, doubly protonated Ala8Arg. This is of interest because doubly protonated tryptic peptides are the most important in proteomics. In comparison with experimental results, our model seriously overpredicts the degree of backbone fragmentation at N9. We offer an improved model that corrects this deficiency. The principal change is to include Coulombic barriers, which hinder the separation of the product cations from each other. Coulombic barriers may be equally important in MS/MS of all multiply charged peptide ions. [Figure not available: see fulltext.

  14. Three novel and the common Arg677Ter RP1 protein truncating mutations causing autosomal dominant retinitis pigmentosa in a Spanish population

    Directory of Open Access Journals (Sweden)

    Antiñolo Guillermo

    2006-04-01

    Full Text Available Abstract Background Retinitis pigmentosa (RP, a clinically and genetically heterogeneous group of retinal degeneration disorders affecting the photoreceptor cells, is one of the leading causes of genetic blindness. Mutations in the photoreceptor-specific gene RP1 account for 3–10% of cases of autosomal dominant RP (adRP. Most of these mutations are clustered in a 500 bp region of exon 4 of RP1. Methods Denaturing gradient gel electrophoresis (DGGE analysis and direct genomic sequencing were used to evaluate the 5' coding region of exon 4 of the RP1 gene for mutations in 150 unrelated index adRP patients. Ophthalmic and electrophysiological examination of RP patients and relatives according to pre-existing protocols were carried out. Results Three novel disease-causing mutations in RP1 were detected: Q686X, K705fsX712 and K722fsX737, predicting truncated proteins. One novel missense mutation, Thr752Met, was detected in one family but the mutation does not co-segregate in the family, thereby excluding this amino acid variation in the protein as a cause of the disease. We found the Arg677Ter mutation, previously reported in other populations, in two independent families, confirming that this mutation is also present in a Spanish population. Conclusion Most of the mutations reported in the RP1 gene associated with adRP are expected to encode mutant truncated proteins that are approximately one third or half of the size of wild type protein. Patients with mutations in RP1 showed mild RP with variability in phenotype severity. We also observed several cases of non-penetrant mutations.

  15. 含有困难氨基酸序列Arg-Arg的醋酸阿基瑞林的固相合成及其动力学研究%Solid Phase Synthesis of Argireline Acetate with Difficult Amino Acid Series Arg-Arg and its Reaction Kinetics

    Institute of Scientific and Technical Information of China (English)

    朱亮亮; 绳则翠; 陈英文; 沈树宝

    2013-01-01

    着重探讨大位阻氨基酸Fmoc-Arg(Pbf)-OH与NH2-Arg(Pbf)-Rink Amide-AM之间的缩合反应,同时对缩合反应进行动力学实验,以期能够获得一条最佳的醋酸阿基瑞林合成路线并对工业化生产进行指导。采用自制新型多肽固相合成反应器,集成过滤、搅拌、控温、鼓泡四重功能。通过对缩合过程中各反应条件的优化,确立了一条最佳的醋酸阿基瑞林合成路线:NMP/DCM(V:V=2:1)为反应溶剂,HBTU/HOBt/DIEA为缩合试剂,氨基酸与树脂摩尔比3:1,40℃下反应2.5 h,粗肽产率高达90.2%。经RP-HPLC分析,醋酸阿基瑞林粗品纯度为83.5%。同时采用微分法对大位阻氨基酸Fmoc-Arg(Pbf)-OH 与NH2-Arg(Pbf)-Rink Amide-AM之间的缩合反应进行动力学研究,测定了温度变化对反应速率的影响,并获得了活化酯方法下缩合反应的宏观动力学参数:反应级数为1.67,表观活化能为37.4 kJ×mol-1。%In order to obtain a best synthetic route of Argireline Acetate and the guidance of its industrial production, this paper focuses on the condensation reaction between sterically hindered amino acid Fmoc-Arg (Pbf)-OH and NH2-Arg(Pbf)-Rink Amide-AM with self-designed reactor, and its kinetic experiments were carried out at the same time. In self-designed reactor, the four functions of filtration, stir, temperature control and bubbling were combined. By optimizing the reaction conditions in the condensation process, a best synthetic route of Argireline Acetate was established, and its optimum reaction conditions were found as follows:the molar ratio of amino acid to resin 3:1, reaction time 2.5 h, temperature 40℃, NMP/DCM (2:1, V/V) as the solvent and HBTU/HOBt/DIEA as coupling reagents. Under above conditions, the highest yield of Argireline Acetate is 90.2%, and its purity is 83.5% by RP-HPLC analysis. The macroscopic kinetics of condensation reaction of Fmoc-Arg-(Pbf)-OH and NH2-Arg(Pbf)-Rink Amide-AM resin

  16. Abundances of tetracycline, sulphonamide and beta-lactam antibiotic resistance genes in conventional wastewater treatment plants (WWTPs) with different waste load

    DEFF Research Database (Denmark)

    Laht, Mailis; Karkman, Antti; Voolaid, Veiko

    2014-01-01

    Antibiotics and antibiotic resistant bacteria enter wastewater treatment plants (WWTPs), an environment where resistance genes can potentially spread and exchange between microbes. Several antibiotic resistance genes (ARGs) were quantified using qPCR in three WWTPs of decreasing capacity located...... conclude that there is neither considerable enrichment nor purification of antibiotic resistance genes in studied conventional WWTPs....... in Helsinki, Tallinn, and Tartu, respectively: sulphonamide resistance genes (sul1 and sul2), tetracycline resistance genes (tetM and tetC), and resistance genes for extended spectrum beta-lactams (blaoxa-58, blashv-34, and blactx-m-32). To avoid inconsistencies among qPCR assays we normalised the ARG...

  17. Normal CBF values by the ARG method using IMP SPECT. Comparison with a conventional microsphere model method

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Hiroshi; Koyama, Masamichi; Kawashima, Ryuta; Ono, Shuichi; Fukuda, Hiroshi [Tohoku Univ., Sendai (Japan). Inst. of Development, Aging and Cancer; Ishii, Kiyoshi; Kinoshita, Toshifumi

    1996-02-01

    N-isopropyl-p[{sup 123}I]iodoamphetamine (IMP) has been used as a flow tracer for SPECT, and measurement of cerebral blood flow (CBF) using IMP has been performed by conventional microsphere model method (MS method). Recently, the ARG method for measuring CBF by using IMP with one SPECT scan and one point blood sampling has been developed. This method was based on two-compartment model. In the present study, normal CBF values were measured in 10 healthy male subjects (mean age{+-}S.D.: 29.8{+-}6.01, age range: 23-41) by ARG and MS methods. The mean CBF values ({+-}S.D.) for ARG method in which V{sub d} value was assumed to be 50 ml/ml were 41.7{+-}9.4, 31.1{+-}5.0, 40.7{+-}9.7, 41.5{+-}10.0, 38.2{+-}9.2, 39.0{+-}9.4, 41.9{+-}10.6, 38.7{+-}8.0 and 30.0{+-}7.7 ml/100 ml/min in the cerebellum, pons, thalamus, basal ganglia, frontal, temporal, parietal, occipital lobe cortex and centrum semiovale, respectively. The mean CBF values for the MS method were 46.8{+-}8.4, 37.5{+-}5.6, 45.8{+-}8.6, 46.5{+-}8.9, 43.7{+-}8.3, 44.4{+-}8.7, 46.8{+-}9.3, 44.3{+-}7.3 and 36.3{+-}8.1 ml/100 ml/min, respectively. The mean CBF values in the cerebral cortex region for ARG method were lower than those previously reported by PET. This would be caused by low first-pass extraction fraction of IMP compared with oxygen-15 labeled water. The mean CBF values for the MS method were higher than those for ARG method against previous studies. As reasons for this, errors in estimation of SPECT brain counts at 8 min in the MS method were considered. (author).

  18. Melanocortin-1 receptor gene variants in four Chinese ethnic populations

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    There is strong relationship between melanocortin-1 receptor (MC1R) gene variants and human hair color and skin type.Based on a sequencing study of MC1R gene in 50 individuals from the Uygur,Tibetan,Wa and Dai ethnic populations,we discuss the occurrence of 7 mc1r variants consisting of 5 nonsynonymous sites (Val60Leu,Arg67Gln,Val92Met,Arg163Gln and Ala299Val) and 2 synonymous sites (C414T and A942G),among which C414T and Ala299Val were reported for the first time.Confirmation and analysis were also made of 122 individuals at three common point mutations (Val92Met,Arg163Gln,A942G) using PCR-SSCP.The frequency of Arg163Gln variant varies in the four ethnic populations,with percentage of 40%,85.0%,66.2% and 72.7%,respectively,while those of Val92Met and A942G are roughly similar in these four populations.The different environments,migration and admixture of various ethnic groups in China might have impact on the observed frequency of Arg163Gln.

  19. Clinical and Prognostic Profiles of Cardiomyopathies Caused by Mutations in the Troponin T Gene.

    Science.gov (United States)

    Ripoll-Vera, Tomás; Gámez, José María; Govea, Nancy; Gómez, Yolanda; Núñez, Juana; Socías, Lorenzo; Escandell, Ángela; Rosell, Jorge

    2016-02-01

    Mutations in the troponin T gene (TTNT2) have been associated in small studies with the development of hypertrophic cardiomyopathy characterized by a high risk of sudden death and mild hypertrophy. We describe the clinical course of patients carrying mutations in this gene. We analyzed the clinical characteristics and prognosis of patients with mutations in the TNNT2 gene who were seen in an inherited cardiac disease unit. Of 180 families with genetically studied cardiomyopathies, 21 families (11.7%) were identified as having mutations in TNNT2: 10 families had Arg92Gln, 5 had Arg286His, 3 had Arg278Cys, 1 had Arg92Trp, 1 had Arg94His, and 1 had Ile221Thr. Thirty-three additional genetic carriers were identified through family assessment. The study included 54 genetic carriers: 56% were male, and the mean average age was 41 ± 17 years. There were 33 cases of hypertrophic cardiomyopathy, 9 of dilated cardiomyopathy, and 1 of noncompaction cardiomyopathy, and maximal myocardial thickness was 18.5 ± 6mm. Ventricular dysfunction was present in 30% of individuals and a history of sudden death in 62%. During follow-up, 4 patients died and 14 (33%) received a defibrillator (8 probands, 6 relatives). Mean survival was 54 years. Carriers of Arg92Gln had early disease development, high penetrance, a high risk of sudden death, a high rate of defibrillator implantation, and a high frequency of mixed phenotype. Mutations in the TNNT2 gene were more common in this series than in previous studies. The clinical and prognostic profiles depended on the mutation present. Carriers of the Arg92Gln mutation developed hypertrophic or dilated cardiomyopathy and had a significantly worse prognosis than those with other mutations in TNNT2 or other sarcomeric genes. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Deletion of Genes Encoding Arginase Improves Use of "Heavy" Isotope-Labeled Arginine for Mass Spectrometry in Fission Yeast.

    Directory of Open Access Journals (Sweden)

    Weronika E Borek

    Full Text Available The use of "heavy" isotope-labeled arginine for stable isotope labeling by amino acids in cell culture (SILAC mass spectrometry in the fission yeast Schizosaccharomyces pombe is hindered by the fact that under normal conditions, arginine is extensively catabolized in vivo, resulting in the appearance of "heavy"-isotope label in several other amino acids, most notably proline, but also glutamate, glutamine and lysine. This "arginine conversion problem" significantly impairs quantification of mass spectra. Previously, we developed a method to prevent arginine conversion in fission yeast SILAC, based on deletion of genes involved in arginine catabolism. Here we show that although this method is indeed successful when (13C6-arginine (Arg-6 is used for labeling, it is less successful when (13C6(15N4-arginine (Arg-10, a theoretically preferable label, is used. In particular, we find that with this method, "heavy"-isotope label derived from Arg-10 is observed in amino acids other than arginine, indicating metabolic conversion of Arg-10. Arg-10 conversion, which severely complicates both MS and MS/MS analysis, is further confirmed by the presence of (13C5(15N2-arginine (Arg-7 in arginine-containing peptides from Arg-10-labeled cells. We describe how all of the problems associated with the use of Arg-10 can be overcome by a simple modification of our original method. We show that simultaneous deletion of the fission yeast arginase genes car1+ and aru1+ prevents virtually all of the arginine conversion that would otherwise result from the use of Arg-10. This solution should enable a wider use of heavy isotope-labeled amino acids in fission yeast SILAC.

  1. Proteomic analysis of the effects of aged garlic extract and its FruArg component on lipopolysaccharide-induced neuroinflammatory response in microglial cells.

    Directory of Open Access Journals (Sweden)

    Hui Zhou

    Full Text Available Aged garlic extract (AGE is widely used as a dietary supplement, and is claimed to promote human health through anti-oxidant/anti-inflammatory activities with hypolipidemic, antiplatelet and neuroprotective effects. Prior studies of AGE have mainly focused on its organosulfur compounds, with little attention paid to its carbohydrate derivatives, such as N-α-(1-deoxy-D-fructos-1-yl-L-arginine (FruArg. The goal of this study is to investigate actions of AGE and FruArg on antioxidative and neuroinflammatory responses in lipopolysaccharide (LPS-activated murine BV-2 microglial cells using a proteomic approach. Our data show that both AGE and FruArg can significantly inhibit LPS-induced nitric oxide (NO production in BV-2 cells. Quantitative proteomic analysis by combining two dimensional differential in-gel electrophoresis (2D-DIGE with mass spectrometry revealed that expressions of 26 proteins were significantly altered upon LPS exposure, while levels of 20 and 21 proteins exhibited significant changes in response to AGE and FruArg treatments, respectively, in LPS-stimulated BV-2 cells. Notably, approximate 78% of the proteins responding to AGE and FruArg treatments are in common, suggesting that FruArg is a major active component of AGE. MULTICOM-PDCN and Ingenuity Pathway Analyses indicate that the proteins differentially affected by treatment with AGE and FruArg are involved in inflammatory responses and the Nrf2-mediated oxidative stress response. Collectively, these results suggest that AGE and FruArg attenuate neuroinflammatory responses and promote resilience in LPS-activated BV-2 cells by suppressing NO production and by regulating expression of multiple protein targets associated with oxidative stress.

  2. Fate and proliferation of typical antibiotic resistance genes in five full-scale pharmaceutical wastewater treatment plants

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jilu [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China); Mao, Daqing, E-mail: mao@tju.edu.cn [School of Environmental Science and Engineering, Tianjin University, Tianjin 300072 (China); Mu, Quanhua [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China); Luo, Yi, E-mail: luoy@nankai.edu.cn [College of Environmental Science and Engineering, Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, Nankai University, Tianjin 300071 (China)

    2015-09-01

    This study investigated the characteristics of 10 subtypes of antibiotic resistance genes (ARGs) for sulfonamide, tetracycline, β-lactam and macrolide resistance and the class 1 integrase gene (intI1). In total, these genes were monitored in 24 samples across each stage of five full-scale pharmaceutical wastewater treatment plants (PWWTPs) using qualitative and real-time quantitative polymerase chain reactions (PCRs). The levels of typical ARG subtypes in the final effluents ranged from (2.08 ± 0.16) × 10{sup 3} to (3.68 ± 0.27) × 10{sup 6} copies/mL. The absolute abundance of ARGs in effluents accounted for only 0.6%–59.8% of influents of the five PWWTPs, while the majority of the ARGs were transported to the dewatered sludge with concentrations from (9.38 ± 0.73) × 10{sup 7} to (4.30 ± 0.81) × 10{sup 10} copies/g dry weight (dw). The total loads of ARGs discharged through dewatered sludge was 7–308 folds higher than that in the raw influents and 16–638 folds higher than that in the final effluents. The proliferation of ARGs mainly occurs in the biological treatment processes, such as conventional activated sludge, cyclic activated sludge system (CASS) and membrane bio-reactor (MBR), implying that significant replication of certain subtypes of ARGs may be attributable to microbial growth. High concentrations of antibiotic residues (ranging from 0.14 to 92.2 mg/L) were detected in the influents of selected wastewater treatment systems and they still remain high residues in the effluents. Partial correlation analysis showed significant correlations between the antibiotic concentrations and the associated relative abundance of ARG subtypes in the effluent. Although correlation does not prove causation, this study demonstrates that in addition to bacterial growth, the high antibiotic residues within the pharmaceutical WWTPs may influence the proliferation and fate of the associated ARG subtypes. - Highlights: • The ARGs in final discharges were 7

  3. Housefly Larva Vermicomposting Efficiently Attenuates Antibiotic Resistance Genes in Swine Manure, with Concomitant Bacterial Population Changes

    Science.gov (United States)

    Wang, Hang; Li, Hongyi; Gilbert, Jack A.; Li, Haibo; Wu, Longhua; Liu, Meng; Wang, Liling; Zhou, Qiansheng; Yuan, Junxiang

    2015-01-01

    Manure from swine treated with antimicrobials as feed additives is a major source for the expansion of the antibiotic resistance gene (ARG) reservoir in the environment. Vermicomposting via housefly larvae (Musca domestica) can be efficiently used to treat manure and regenerate biofertilizer, but few studies have investigated its effect on ARG attenuation. Here, we tracked the abundances of 9 ARGs and the composition and structure of the bacterial communities in manure samples across 6 days of full-scale manure vermicomposting. On day 6, the abundances of genes encoding tetracycline resistance [tet(M), tet(O), tet(Q), and tet(W)] were reduced (P vermicomposting, accompanied by a 100 times increase in the relative abundance of Flavobacteriaceae spp. Variations in the abundances of ARGs were correlated with the changing microbial community structure and the relative abundances of the family Ruminococcaceae, class Bacilli, or phylum Proteobacteria. Vermicomposting, as a waste management practice, can reduce the overall abundance of ARGs. More research is warranted to assess the use of this waste management practice as a measure to attenuate the dissemination of antimicrobial residues and ARGs from livestock production before vermicompost can be safely used as biofertilizer in agroecosystems. PMID:26296728

  4. Structural and population-based evaluations of TBC1D1 p.Arg125Trp.

    Directory of Open Access Journals (Sweden)

    Tom G Richardson

    Full Text Available Obesity is now a leading cause of preventable death in the industrialised world. Understanding its genetic influences can enhance insight into molecular pathogenesis and potential therapeutic targets. A non-synonymous polymorphism (rs35859249, p.Arg125Trp in the N-terminal TBC1D1 phosphotyrosine-binding (PTB domain has shown a replicated association with familial obesity in women. We investigated these findings in the Avon Longitudinal Study of Parents and Children (ALSPAC, a large European birth cohort of mothers and offspring, and by generating a predicted model of the structure of this domain. Structural prediction involved the use of three separate algorithms; Robetta, HHpred/MODELLER and I-TASSER. We used the transmission disequilibrium test (TDT to investigate familial association in the ALSPAC study cohort (N = 2,292 mother-offspring pairs. Linear regression models were used to examine the association of genotype with mean measurements of adiposity (Body Mass Index (BMI, waist circumference and Dual-energy X-ray absorptiometry (DXA assessed fat mass, and logistic regression was used to examine the association with odds of obesity. Modelling showed that the R125W mutation occurs in a location of the TBC1D1 PTB domain that is predicted to have a function in a putative protein:protein interaction. We did not detect an association between R125W and BMI (mean per allele difference 0.27 kg/m(2 (95% Confidence Interval: 0.00, 0.53 P = 0.05 or obesity (odds ratio 1.01 (95% Confidence Interval: 0.77, 1.31, P = 0.96 in offspring after adjusting for multiple comparisons. Furthermore, there was no evidence to suggest that there was familial association between R125W and obesity (χ(2 = 0.06, P = 0.80. Our analysis suggests that R125W in TBC1D1 plays a role in the binding of an effector protein, but we find no evidence that the R125W variant is related to mean BMI or odds of obesity in a general population sample.

  5. Ultraviolet disinfection of antibiotic resistant bacteria and their antibiotic resistance genes in water and wastewater.

    Science.gov (United States)

    McKinney, Chad W; Pruden, Amy

    2012-12-18

    Disinfection of wastewater treatment plant effluent may be an important barrier for limiting the spread of antibiotic-resistant bacteria (ARBs) and antibiotic resistance genes (ARGs). While ideally disinfection should destroy ARGs, to prevent horizontal gene transfer to downstream bacteria, little is known about the effect of conventional water disinfection technologies on ARGs. This study examined the potential of UV disinfection to damage four ARGs, mec(A), van(A), tet(A), and amp(C), both in extracellular form and present within a host ARBs: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), Escherichia coli SMS-3-5, and Pseudomonas aeruginosa 01, respectively. An extended amplicon-length quantitative polymerase chain reaction assay was developed to enhance capture of ARG damage events and also to normalize to an equivalent length of target DNA (∼1000 bp) for comparison. It was found that the two Gram-positive ARBs (MRSA and VRE) were more resistant to UV disinfection than the two Gram-negative ARBs (E. coli and P. aeruginosa). The two Gram-positive organisms also possessed smaller total genome sizes, which could also have reduced their susceptibility to UV because of fewer potential pyrimidine dimer targets. An effect of cell type on damage to ARGs was only observed in VRE and P. aeruginosa, the latter potentially because of extracellular polymeric substances. In general, damage of ARGs required much greater UV doses (200-400 mJ/cm² for 3- to 4-log reduction) than ARB inactivation (10-20 mJ/cm² for 4- to 5-log reduction). The proportion of amplifiable ARGs following UV treatment exhibited a strong negative correlation with the number of adjacent thymines (Pearson r 0.85; p disinfection technologies should be explored.

  6. The [Lys(-2)-Arg(-1)-des(17-21)]-endothelin-1 peptide retains the specific Arg(-1)-Asp8 salt bridge but reveals discrepancies between NMR data and molecular dynamics simulations.

    Science.gov (United States)

    Kaas, Quentin; Aumelas, André; Kubo, Shigeru; Chino, Naoyoshi; Kobayashi, Yuji; Chiche, Laurent

    2002-09-17

    The [des(17-21)]-endothelin-1 (CSH-ET) and [Lys(-)(2)-Arg(-)(1)-des(17-21)]-endothelin-1 (KR-CSH-ET) peptides, designed by removing the five-residue hydrophobic tail from the endothelin-1 (ET-1) and [Lys(-)(2)-Arg(-)(1)]-endothelin-1 (KR-ET-1) peptides, respectively, were synthesized. Previous studies on KR-ET-1 showed that, in contrast to ET-1, this engineered compound displays a pH-dependent conformational change related to the formation of a stabilizing salt bridge between the Arg(-)(1) and Asp(8) side chains. CD and NMR spectra indicate that CSH-ET and KR-CSH-ET display conformational behavior similar to those of ET-1 and KR-ET-1, respectively. The short salt bridge-stabilized KR-CSH-ET peptide therefore appears to be an attractive elementary scaffold for drug design. The solution structure of the salt-bridged form of KR-CSH-ET was determined by NMR at pH 4.5 and is very similar to the corresponding form of the parent KR-ET-1 peptide. Molecular dynamics simulations of the salt-bridged form of KR-CSH-ET were performed using both the GB/SA implicit solvation scheme or an explicit solvation and the particle-mesh Ewald method for long-range electrostatic calculation. Unexpectedly, the Arg(-)(1)-Asp(8) salt bridge does not display in the simulation the stability that could be expected from the experimental data. The cooperative involvement of a cation-pi interaction in formation of the salt bridge has been hypothesized. Difficulties in accurately simulating cation-pi interactions might be responsible for the lack of stability in the simulation. At this time, however, no definitive explanation for the observed discrepancy between experiments and simulations is available, and further experimental studies appear to be necessary to fully understand in atomic detail the pH-dependent conformational change observed in the KR-ET-1 series.

  7. Effects of full-scale advanced water treatment on antibiotic resistance genes in the Yangtze Delta area in China.

    Science.gov (United States)

    Zhang, Shuting; Lin, Wenfang; Yu, Xin

    2016-05-01

    As emerging microbial contaminants, antibiotic resistance genes (ARGs) are widespread in the aquatic environment, including source water, which might enter water supply systems and endanger public health by enhancing the resistance of opportunistic pathogens to some antibiotics. In the present study, we investigated how water treatments affect the levels of ARGs in a full-scale drinking water treatment plant for one year using real-time PCR. The 16s rRNA gene and eleven ARG families, including tetA, tetG, aacC1, strA, ermB, cmlA5, vanA, dfrA1, sulII, blaTEM-1 and blaoxa-1, in source water and the outlet of each treatment and tap water were monitored. The results showed that nine ARG families were detected at relatively high levels, for example, the sulII gene was detected at ∼10(4) copies mL(-1) compared with 10(5) copies mL(-1) in finished water and tap water in July, whose relative concentrations were consistently high. Treatments for the reduction of the absolute concentrations of ARGs included sand filtration, coagulation/sedimentation and two-stage O3-BAC filtration, while distribution could increase ARGs an average of 0.50 log.

  8. Metagenomic analysis of bacterial community composition and antibiotic resistance genes in a wastewater treatment plant and its receiving surface water.

    Science.gov (United States)

    Tang, Junying; Bu, Yuanqing; Zhang, Xu-Xiang; Huang, Kailong; He, Xiwei; Ye, Lin; Shan, Zhengjun; Ren, Hongqiang

    2016-10-01

    The presence of pathogenic bacteria and the dissemination of antibiotic resistance genes (ARGs) may pose big risks to the rivers that receive the effluent from municipal wastewater treatment plants (WWTPs). In this study, we investigated the changes of bacterial community and ARGs along treatment processes of one WWTP, and examined the effects of the effluent discharge on the bacterial community and ARGs in the receiving river. Pyrosequencing was applied to reveal bacterial community composition including potential bacterial pathogen, and Illumina high-throughput sequencing was used for profiling ARGs. The results showed that the WWTP had good removal efficiency on potential pathogenic bacteria (especially Arcobacter butzleri) and ARGs. Moreover, the bacterial communities of downstream and upstream of the river showed no significant difference. However, the increase in the abundance of potential pathogens and ARGs at effluent outfall was observed, indicating that WWTP effluent might contribute to the dissemination of potential pathogenic bacteria and ARGs in the receiving river. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Influencia del polimorfismo Gln223Arg del receptor de leptina en el sobrepeso

    OpenAIRE

    2011-01-01

    En la mayoría de las situaciones el sobrepeso/obesidad tiene un carácter poligénico, con múltiples genes implicados, con interacciones entre ellos y con el ambiente, sin que hasta la fecha se haya podido cuantificar la contribución real de cada uno de esos factores. Existen, sin embargo, grupos de genes que parecen ser determinantes en relación a la predisposición a los estados de sobrepeso. Entre los múltiples genes determinantes en la obesidad destacan aquellos implicados ...

  10. Synthesis of Fluorine-18 Labeled Glucose-Lys-Arg-Gly-Asp-D-Phe as a Potential Tumor Imaging Agent

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyo Chul; Kim, Ji Sun; Sung, Hyun Ju; Jung, Jae Ho; An, Gwang Il; Chi, Dae Yoon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Byung Chul; Moon, Byung Seok; Choi, Tae Hyun; Chuna, Kwon Soo [Inha Univ., Inchon (Korea, Republic of)

    2005-07-01

    The {alpha}{sub v}{beta}{sub 3} integrin is an important receptor affecting tumor growth, metastatic potential on proliferating endothelial cells as well as on tumor cells of various origin, tumor-induced angiogenesis could be blocked by antagonizing the {alpha}{sub v}{beta}{sub 3} integrin with RGD. Therefore, {alpha}{sub v}{beta}{sub 3} integrin is a target for angiogenesis imaging that might be useful in assessing tumor-induced angiogenesis and identifying tumor metastasis. To design potent radiotracer for imaging angiogenesis containing a cRGD moiety should include low hepatic uptake in vivo. Tripeptide Arg-Gly-Asp (RGD), naturally existed in extracellular matrix proteins, is known to be the primary binding site of the {alpha}{sub v}{beta}{sub 3} integrin. The imaging of {alpha}{sub v}{beta}{sub 3} receptor expression will give the information of the metastatic ability of the tumor which is not available by [{sup 18}F]FDG. Our interest in developing new radiopharmaceuticals for in vivo visualization of angiogenesis has led us to synthesize derivatives of cRGD (cyclic arginineglycine-aspartic acid) that contains glucose moiety. Because sugar-protein interaction is a key step in metastasis and angiogenesis, it has also been proposed to play an intriguing role in imaging of tumor. We designed and synthesized two fluorine-18 labeled RGD glycopeptides . N-fluorobenzyl-diaminobutane-N'-glucose-Lys-Arg-Gly-Asp-D-Phe ([{sup 18}F]fluorobenzyl-glucose-KRGDf, and Nfluorobenzoyl- diaminobutane-N'-glucose-Lys-Arg-Gly-Asp-D-Phe ([{sup 18}F]fluorobenzoyl-glucose-KRGDf, from same precursor as a diagnostic tumor imaging agent for positron emission tomography (PET). Fluorine-18 labeled cRGD glycopeptides were prepared using two different simple labeling methods: one is reductive alkylation of an amine with [{sup 18}F]fluorobenzaldehyde and the other is amide condensation with [{sup 18}F]fluorobenzoic acid.

  11. Identification of Minor Secondary Metabolites from the Latex of Croton lechleri (Muell-Arg) and Evaluation of Their Antioxidant Activity

    OpenAIRE

    Maria Iorizzi; Francesco Visioli; Gelsomina Fico; Sara Vitalini; Franco Zollo; Fulvio Gala; Simona De Marino

    2008-01-01

    Dragon’s blood (Sangre de drago), a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae), is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ol...

  12. Antibiotic resistance genes in bacterial and bacteriophage fractions of Tunisian and Spanish wastewaters as markers to compare the antibiotic resistance patterns in each population.

    Science.gov (United States)

    Colomer-Lluch, Marta; Calero-Cáceres, William; Jebri, Sihem; Hmaied, Fatma; Muniesa, Maite; Jofre, Juan

    2014-12-01

    The emergence and increased prevalence of antibiotic resistance genes (ARGs) in the environment may pose a serious global health concern. This study evaluates the abundance of several ARGs in bacterial and bacteriophage DNA via real-time qPCR in samples from five different sampling points in Tunisia; three wastewater treatment plants (WWTP 1, 2 and 3) and wastewater from two abattoirs slaughtering different animals. Results are compared with those obtained in the Barcelona area, in northeast Spain. Eight ARGs were quantified by qPCR from total and phage DNA fraction from the samples. Three β-lactamases (bla(TEM), bla(CTX-M) cluster 1 and bla(CTX-M) cluster 9), two quinolone resistance genes (qnrA and qnrS), the mecA gene that confers resistance to methicillin in Staphylococcus aureus, the emerging armA gene, conferring resistance to aminoglycosides and sul1, the most extended gene conferring resistance to sulfonamides, were evaluated. Sul1 and bla(TEM) were the most prevalent ARGs detected at all five Tunisian sampling points, similarly with the observations in Barcelona. bla(CTX-M-9) was more prevalent than bla(CTX-M-1) both in bacterial and DNA within phage particles in all samples analysed. mecA and armA were almost absent in Tunisian waters from human or animal origin in contrast with Barcelona that showed a medium prevalence. qnrA was more prevalent than qnrS in bacterial and phage DNA from all sampling points. In conclusion, our study shows that ARGs are found in the bacterial and is reflected in the phage DNA fraction of human and animal wastewaters. The densities of each ARGs vary depending on the ARGs shed by each population and is determined by the characteristics of each area. Thus, the evaluation of ARGs in wastewaters seems to be suitable as marker reflecting the antibiotic resistance patterns of a population.

  13. Occurrence of antibiotics and antibiotic resistance genes in hospital and urban wastewaters and their impact on the receiving river.

    Science.gov (United States)

    Rodriguez-Mozaz, Sara; Chamorro, Sara; Marti, Elisabet; Huerta, Belinda; Gros, Meritxell; Sànchez-Melsió, Alexandre; Borrego, Carles M; Barceló, Damià; Balcázar, Jose Luis

    2015-02-01

    Antibiotic resistance has become a major health concern; thus, there is a growing interest in exploring the occurrence of antibiotic resistance genes (ARGs) in the environment as well as the factors that contribute to their emergence. Aquatic ecosystems provide an ideal setting for the acquisition and spread of ARGs due to the continuous pollution by antimicrobial compounds derived from anthropogenic activities. We investigated, therefore, the pollution level of a broad range of antibiotics and ARGs released from hospital and urban wastewaters, their removal through a wastewater treatment plant (WWTP) and their presence in the receiving river. Several antimicrobial compounds were detected in all water samples collected. Among antibiotic families, fluoroquinolones were detected at the highest concentration, especially in hospital effluent samples. Although good removal efficiency by treatment processes was observed for several antimicrobial compounds, most antibiotics were still present in WWTP effluents. The results also revealed that copy numbers of ARGs, such as blaTEM (resistance to β-lactams), qnrS (reduced susceptibility to fluoroquinolones), ermB (resistance to macrolides), sulI (resistance to sulfonamides) and tetW (resistance to tetracyclines), were detected at the highest concentrations in hospital effluent and WWTP influent samples. Although there was a significant reduction in copy numbers of these ARGs in WWTP effluent samples, this reduction was not uniform across analyzed ARGs. Relative concentration of ermB and tetW genes decreased as a result of wastewater treatment, whereas increased in the case of blaTEM, sulI and qnrS genes. The incomplete removal of antibiotics and ARGs in WWTP severely affected the receiving river, where both types of emerging pollutants were found at higher concentration in downstream waters than in samples collected upstream from the discharge point. Taken together, our findings demonstrate a widespread occurrence of

  14. 纤维蛋白原γ链Arg275His突变所致异常纤维蛋白原的功能研究%Functional study of abnormal fibrinogen caused by Arg275His mutation in fibrinogen γchain

    Institute of Scientific and Technical Information of China (English)

    周景艺; 王学锋; 丁秋兰; 许冠群; 张利伟; 戴菁; 陆晔玲; 奚晓东; 王鸿利

    2013-01-01

    目的 对两个遗传性异常纤维蛋白原血症家系的突变纤维蛋白原(Fg)进行功能研究.方法 常规筛查凝血功能;Fg抗原和活性分别用免疫比浊法和Clauss法测定;抽提DNA,对Fg 3个基因(FGA、FGB和FGG)以及抗凝血酶基因(AT3)所有外显子及侧翼序列进行PCR扩增、测序及分析;采用常规血栓弹力图(TEG)和功能性FgTEG检查对家系B先证者及其父亲进行凝血功能的综合评价及血浆功能性Fg评估;应用Western blot检测血浆Fg肽链分子量;采用Fg动态聚集曲线和纤维蛋白溶解曲线实验检测血浆Fg的功能.结果 2例先证者凝血酶原时间(TT)和爬虫酶凝固时间(RT)明显延长,Fg活性仅为0.5 g/L和0.6 g/L,但其抗原均正常,分别为2.32 g/L和2.66 g/L.两个家系先证者均存在γ链Arg275His杂合突变,家系B先证者的祖父和姑母同时检出AT3 g.5876T>C(Ser116Pro)杂合突变.家系B先证者及其父亲TEG检测结果中α值分别接近和低于正常参考值范围下限,但最大波幅(MA值)均为正常;在功能性Fg TEG检测中,MA值明显偏低.Fg动态聚集曲线中先证者和家系患者的起跳时间明显延长、峰值明显降低.纤维蛋白溶解曲线中多数患者的纤维蛋白在特定时间内不能被纤溶酶原完全溶解.结论 首次发现遗传性异常纤维蛋白原血症合并AT缺陷的患者.γ链Arg275 His突变使Fg在纤维蛋白单体聚合以及纤维蛋白溶解方面出现异常.联合应用常规TEG和功能性TEG检测,可以更好地评估异常纤维蛋白原血症患者Fg的功能.%Objective To investigate the function of abnormal fibrinogen in two inherited dysfibrinogenemia pedigrees.Methods Routine coagulation tests were conducted in the probands and related family members.The antigen and activity levels of fibrinogen were detected by immunoturbidimetry assay and clauss assay,respectively.All the exons and exon-intron boundaries of the three fibrinogen genes and antithrombin gene (AT3

  15. Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome amongst the Taiwanese population- not correlated with insulin receptor substrate-1 Gly972Arg/Ala513Pro polymorphism

    Directory of Open Access Journals (Sweden)

    Liang Shu-Fen

    2006-04-01

    Full Text Available Abstract Background Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS proteins, especially Gly972Arg/Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS. We intended to assess the prevalence of abnormal glucose tolerance (AGT and insulin resistance in Taiwanese PCOS women. We also tried to assess whether the particular identity of Gly972Arg/Ala513Pro polymorphic alleles of the IRS-1 gene mutation can be used as an appropriate diagnostic indicator for PCOS. Methods We designed a prospective clinical study. Forty-seven Taiwanese Hoklo and Hakka women, diagnosed with PCOS were enrolled in this study as were forty-five healthy Hoklo and Hakka women as the control group. Insulin resistance was evaluated with fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment index for insulin resistance (HOMAIR. The genomic DNA of the subjects was amplified by PCR and digested by restriction fragmented length polymorphism (RFLP with Bst N1 used for codon 972 and Dra III for codon 513. Results AGT was found in 46.8% of these PCOS patients and was significantly related to high insulin resistance rather than the low insulin resistance. Those patients with either insulin resistance or AGT comprised the majority of PCOS affected patients (AGT + fasting insulin ≥17: 83%, AGT + glucose/insulin ratio ≥6.5: 85.1%, AGT + HOMAIR ≥ 2: 87.2%, and AGT + HOMAIR ≥ 3.8: 72.3%. None of the tested samples revealed any polymorphism due to the absence of any Dra III recognition site or any Bst N1 recognition site in the amplified PCR fragment digested by restriction fragmented length polymorphism. Conclusion There is significantly high prevalence of AGT and insulin resistance in PCOS women, but Gly972Arg and Ala513Pro polymorphic alleles of IRS-1 are rare and are not associated with the elevated

  16. Lack of association between the Trp719Arg polymorphism in kinesin-like protein 6 and coronary artery disease in 19 case-control studies

    Science.gov (United States)

    Assimes, Themistocles L; Hólm, Hilma; Kathiresan, Sekar; Reilly, Muredach P; Thorleifsson, Gudmar; Voight, Benjamin F; Erdmann, Jeanette; Willenborg, Christina; Vaidya, Dhananjay; Xie, Changchun; Patterson, Chris C; Morgan, Thomas M; Burnett, Mary Susan; Li, Mingyao; Hlatky, Mark A; Knowles, Joshua W; Thompson, John R; Absher, Devin; Iribarren, Carlos; Go, Alan; Fortmann, Stephen P; Sidney, Stephen; Risch, Neil; Tang, Hua; Myers, Richard M; Berger, Klaus; Stoll, Monika; Shah, Svati H.; Thorgeirsson, Gudmundur; Andersen, Karl; Havulinna, Aki S; Herrera, J. Enrique; Faraday, Nauder; Kim, Yoonhee; Kral, Brian G.; Mathias, Rasika; Ruczinski, Ingo; Suktitipat, Bhoom; Wilson, Alexander F; Yanek, Lisa R.; Becker, Lewis C; Linsel-Nitschke, Patrick; Lieb, Wolfgang; König, Inke R; Hengstenberg, Christian; Fischer, Marcus; Stark, Klaus; Reinhard, Wibke; Winogradow, Janina; Grassl, Martina; Grosshennig, Anika; Preuss, Michael; Eifert, Sandra; Schreiber, Stefan; Wichmann, H-Erich; Meisinger, Christa; Yee, Jean; Friedlander, Yechiel; Do, Ron; Meigs, James B; Williams, Gordon; Nathan, David M; MacRae, Calum A; Qu, Liming; Wilensky, Robert L; Matthai, William H.; Qasim, Atif N; Hakonarson, Hakon; Pichard, Augusto D; Kent, Kenneth M; Satler, Lowell; Lindsay, Joseph M; Waksman, Ron; Knouff, Christopher W; Waterworth, Dawn M; Walker, Max C; Mooser, Vincent; Marrugat, Jaume; Lucas, Gavin; Subirana, Isaac; Sala, Joan; Ramos, Rafael; Martinelli, Nicola; Olivieri, Oliviero; Trabetti, Elisabetta; Malerba, Giovanni; Pignatti, Pier Franco; Guiducci, Candace; Mirel, Daniel; Parkin, Melissa; Hirschhorn, Joel N; Asselta, Rosanna; Duga, Stefano; Musunuru, Kiran; Daly, Mark J; Purcell, Shaun; Braund, Peter S; Wright, Benjamin J; Balmforth, Anthony J; Ball, Stephen G; Ouwehand, Willem H; Deloukas, Panos; Scholz, Michael; Cambien, Francois; Huge, Andreas; Scheffold, Thomas; Salomaa, Veikko; Girelli, Domenico; Granger, Christopher B.; Peltonen, Leena; McKeown, Pascal P; Altshuler, David; Melander, Olle; Devaney, Joseph M; Epstein, Stephen E; Rader, Daniel J; Elosua, Roberto; Engert, James C; Anand, Sonia S; Hall, Alistair S; Ziegler, Andreas; O’Donnell, Christopher J; Spertus, John A; Siscovick, David; Schwartz, Stephen M; Becker, Diane; Thorsteinsdottir, Unnur; Stefansson, Kari; Schunkert, Heribert; Samani, Nilesh J; Quertermous, Thomas

    2011-01-01

    Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455) and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with non-carriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in nineteen case-control studies of non-fatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results Over 17 000 cases and 39 000 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the nineteen studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with non-carriers. Regression analyses and fixed effect meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early onset disease (<50 years of age for males and <60 years for females) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. PMID:20933357

  17. Antibiotic Resistance Genes and Correlations with Microbial Community and Metal Resistance Genes in Full-Scale Biogas Reactors As Revealed by Metagenomic Analysis

    DEFF Research Database (Denmark)

    Luo, Gang; Li, Bing; Li, Li-Guan

    2017-01-01

    Digested residues from biogas plants are often used as biofertilizers for agricultural crops cultivation. The antibiotic resistance genes (ARGs) in digested residues pose a high risk to public health due to their potential spread to the disease-causing microorganisms and thus reduce the susceptib......Digested residues from biogas plants are often used as biofertilizers for agricultural crops cultivation. The antibiotic resistance genes (ARGs) in digested residues pose a high risk to public health due to their potential spread to the disease-causing microorganisms and thus reduce...

  18. Inactivation of antibiotic resistance genes in municipal wastewater effluent by chlorination and sequential UV/chlorination disinfection

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingying; Zhuang, Yao; Geng, Jinju, E-mail: jjgeng@nju.edu.cn; Ren, Hongqiang, E-mail: hqren@nju.edu.cn; Zhang, Yan; Ding, Lili; Xu, Ke

    2015-04-15

    This study investigated disinfection methods including chlorination, ultraviolet (UV) irradiation and sequential UV/chlorination treatment on the inactivation of antibiotic resistance genes (ARGs). ARGs including sul1, tetX, tetG, intI1, and 16S rRNA genes in municipal wastewater treatment plant (MWTP) effluent were examined. The results indicated a positive correlation between the removal of ARGs and chlorine dosage (p = 0.007–0.014, n = 6),as well as contact time (p = 0.0001, n = 10). Greater free chlorine (FC) dosage leads to higher removal for all the genes and the maximum removal (1.30–1.49 logs) could be achieved at FC dosage of 30 mg L{sup −1}. The transformation kinetic data for ARGs removal (log C{sub 0} / C) followed the second-order reaction kinetic model with FC dosage (R{sup 2} = 0.6829–0.9999) and contact time (R{sup 2} = 0.7353–8634), respectively. Higher ammonia nitrogen (NH{sub 3}–N) concentration was found to lead to lower removal of ARGs at the same chlorine dosage. When the applied Cl{sub 2}:NH{sub 3}–N ratio was over 7.6:1, a significant reduction of ARGs (1.20–1.49 logs) was achieved. By using single UV irradiation, the log removal values of tetX and 16Ss rRNA genes were 0.58 and 0.60, respectively, while other genes were 0.36–0.40 at a fluence of 249.5 mJ cm{sup −2}, which was observed to be less effective than chlorination. With sequential UV/chlorination treatment, 0.006 to 0.31 log synergy values of target genes were observed under different operation parameters. - Highlights: • Chlorine is more effective than UV irradiation in removing ARGs from MWTP effluent. • The chlorination reaction followed the second-order reaction kinetic model. • Higher NH{sub 3}–N contents result in lower ARGs removal in the chlorination process. • FC is more effective than CC on the inactivation of ARGs. • UV irradiation followed by chlorination shows high efficiency in removing ARGs.

  19. Hypokalemic periodic paralysis; two different genes responsible for similar clinical manifestations.

    Science.gov (United States)

    Kim, Hunmin; Hwang, Hee; Cheong, Hae Il; Park, Hye Won

    2011-11-01

    Primary hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disorder manifesting as recurrent periodic flaccid paralysis and concomitant hypokalemia. HOKPP is divided into type 1 and type 2 based on the causative gene. Although 2 different ion channels have been identified as the molecular genetic cause of HOKPP, the clinical manifestations between the 2 groups are similar. We report the cases of 2 patients with HOKPP who both presented with typical clinical manifestations, but with mutations in 2 different genes (CACNA1Sp.Arg528His and SCN4A p.Arg672His). Despite the similar clinical manifestations, there were differences in the response to acetazolamide treatment between certain genotypes of SCN4A mutations and CACNA1S mutations. We identified p.Arg672His in the SCN4A gene of patient 2 immediately after the first attack through a molecular genetic testing strategy. Molecular genetic diagnosis is important for genetic counseling and selecting preventive treatment.

  20. Effect of red mud addition on tetracycline and copper resistance genes and microbial community during the full scale swine manure composting.

    Science.gov (United States)

    Wang, Rui; Zhang, Junya; Sui, Qianwen; Wan, Hefeng; Tong, Juan; Chen, Meixue; Wei, Yuansong; Wei, Dongbin

    2016-09-01

    Swine manure has been considered as the reservoir of antibiotic resistance genes (ARGs). Composting is one of the most suitable technologies for treating livestock manures, and red mud was proved to have a positive effect on nitrogen conservation during composting. This study investigated the abundance of eight tetracycline and three copper resistance genes, the bacterial community during the full scale swine manure composting with or without addition of red mud. The results showed that ARGs in swine manure could be effectively removed through composting (reduced by 2.4log copies/g TS), especially during the thermophilic phase (reduced by 1.5log copies/g TS), which the main contributor might be temperature. Additionally, evolution of bacterial community could also have a great influence on ARGs. Although addition of red mud could enhance nitrogen conservation, it obviously hindered removal of ARGs (reduced by 1.7log copies/g TS) and affected shaping of bacterial community during composting.

  1. Impact of bioaccessible pyrene on the abundance of antibiotic resistance genes during Sphingobium sp.- and sophorolipid-enhanced bioremediation in soil.

    Science.gov (United States)

    Sun, Mingming; Ye, Mao; Wu, Jun; Feng, Yanfang; Shen, Fangyuan; Tian, Da; Liu, Kuan; Hu, Feng; Li, Huixin; Jiang, Xin; Yang, Linzhang; Kengara, Fredrick Orori

    2015-12-30

    Soils are exposed to various types of chemical contaminants due to anthropogenic activities; however, research on persistent organic pollutants and the existence of antibiotic resistance genes (ARGs) is limited. To our knowledge, the present work for the first time focused on the bioremediation of soil co-contaminated with pyrene and tetracycline/sulfonamide-resistance genes. After 90 days of incubation, the pyrene concentration and the abundance of the four ARGs (tetW, tetM, sulI, and sulII) significantly decreased in different treatment conditions (psoil treated with sophorolipid alone. Tenax extraction methods and linear correlation analysis indicated a strong positive relationship between the rapidly desorbing fraction (Fr) of pyrene and ARG abundance. Therefore, we conclude that bioaccessible pyrene rather than total pyrene plays a major role in the maintenance and fluctuation of ARG abundance in the soil.

  2. A Review on the Salt Bridge Between ASP177 and ARG163 of Wild-Type Rabbit Prion Protein

    CERN Document Server

    Zhang, Jiapu

    2014-01-01

    Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect a wide variety of mammalian species such as sheep and goats, cattle, deer, elks, humans and mice etc., but rabbits have a low susceptibility to be infected by prion diseases with respect to other species. The stability of rabbit prion protein is due to its highly ordered beta2-alpha2 loop [PLoS One 5 (10) e13273 (2010); Journal of Biological Chemistry 285 (41) 31682-31693 (2010)] and a helix-capping motif within this loop [PLoS One 8 (5) e63047 (2013)]. The beta2-alpha2 loop has been a focus in prion studies. For this loop we found a salt bridge linkage ASP177-ARG163 (O-N) [Journal of Theoretical Biology 342 (7 February 2014) 70-82 (2014)]. Some scientists said on the 2FJ3.pdb NMR file of the rabbit prion protein, the distance of ASP177-ARG163 (O-N) gives the salt bridge of about 10 angstroms which is nearly null in terms of energy thus think our result is wrong. This opinion is clearly wrong simply due to the 3O7...

  3. The Lys234Arg Substitution in the Enzyme SHV-72 Is a Determinant for Resistance to Clavulanic Acid Inhibition▿

    Science.gov (United States)

    Mendonça, Nuno; Manageiro, Vera; Robin, Frédéric; Salgado, M. José; Ferreira, Eugénia; Caniça, Manuela; Bonnet, Richard

    2008-01-01

    The new β-lactamase SHV-72 was isolated from clinical Klebsiella pneumoniae INSRA1229, which exhibited the unusual association of resistance to the amoxicillin-clavulanic acid combination (MIC, 64 μg/ml) and susceptibility to cephalosporins, aztreonam, and imipenem. SHV-72 (pI 7.6) harbored the three amino acid substitutions Ile8Phe, Ala146Val, and Lys234Arg. SHV-72 had high catalytic efficiency against penicillins (kcat/Km, 35 to 287 μM−1·s−1) and no activity against oxyimino β-lactams. The concentration of clavulanic acid necessary to inhibit the enzyme activity by 50% was 10-fold higher for SHV-72 than for SHV-1. Molecular-dynamics simulation suggested that the Lys234Arg substitution in SHV-72 stabilized an atypical conformation of the Ser130 side chain, which moved the Oγ atom of Ser130 around 3.5 Å away from the key Oγ atom of the reactive serine (Ser70). This movement may therefore decrease the susceptibility to clavulanic acid by preventing cross-linking between Ser130 and Ser70. PMID:18316518

  4. Cationic amino acid transporters and Salmonella Typhimurium ArgT collectively regulate arginine availability towards intracellular Salmonella growth.

    Directory of Open Access Journals (Sweden)

    Priyanka Das

    Full Text Available Cationic amino acid transporters (mCAT1 and mCAT2B regulate the arginine availability in macrophages. How in the infected cell a pathogen can alter the arginine metabolism of the host remains to be understood. We reveal here a novel mechanism by which Salmonella exploit mCAT1 and mCAT2B to acquire host arginine towards its own intracellular growth within antigen presenting cells. We demonstrate that Salmonella infected bone marrow derived macrophages and dendritic cells show enhanced arginine uptake and increased expression of mCAT1 and mCAT2B. We show that the mCAT1 transporter is in close proximity to Salmonella containing vacuole (SCV specifically by live intracellular Salmonella in order to access the macrophage cytosolic arginine pool. Further, Lysosome associated membrane protein 1, a marker of SCV, also was found to colocalize with mCAT1 in the Salmonella infected cell. The intra vacuolar Salmonella then acquire the host arginine via its own arginine transporter, ArgT for growth. The argT knockout strain was unable to acquire host arginine and was attenuated in growth in both macrophages and in mice model of infection. Together, these data reveal survival strategies by which virulent Salmonella adapt to the harsh conditions prevailing in the infected host cells.

  5. Dissemination of veterinary antibiotics and corresponding resistance genes from a concentrated swine feedlot along the waste treatment paths.

    Science.gov (United States)

    Wang, Jian; Ben, Weiwei; Yang, Min; Zhang, Yu; Qiang, Zhimin

    2016-01-01

    Swine feedlots are an important pollution source of antibiotics and antibiotic resistance genes (ARGs) to the environment. This study investigated the dissemination of two classes of commonly-used veterinary antibiotics, namely, tetracyclines (TCs) and sulfonamides (SAs), and their corresponding ARGs along the waste treatment paths from a concentrated swine feedlot located in Beijing, China. The highest total TC and total SA concentrations detected were 166.7mgkg(-1) and 64.5μgkg(-1) in swine manure as well as 388.7 and 7.56μgL(-1) in swine wastewater, respectively. Fourteen tetracycline resistance genes (TRGs) encoding ribosomal protection proteins (RPP), efflux proteins (EFP) and enzymatic inactivation proteins, three sulfonamide resistance genes (SRGs), and two integrase genes were detected along the waste treatment paths with detection frequencies of 33.3-75.0%. The relative abundances of target ARGs ranged from 2.74×10(-6) to 1.19. The antibiotics and ARGs generally declined along both waste treatment paths, but their degree of reduction was more significant along the manure treatment path. The RPP TRGs dominated in the upstream samples and then decreased continuously along both waste treatment paths, whilst the EFP TRGs and SRGs maintained relatively stable. Strong correlations between antibiotic concentrations and ARGs were observed among both manure and wastewater samples. In addition, seasonal temperature, and integrase genes, moisture content and nutrient level of tested samples could all impact the relative abundances of ARGs along the swine waste treatment paths. This study helps understand the evolution and spread of ARGs from swine feedlots to the environment as well as assess the environmental risk arising from swine waste treatment.

  6. Long-term field application of sewage sludge increases the abundance of antibiotic resistance genes in soil.

    Science.gov (United States)

    Chen, Qinglin; An, Xinli; Li, Hu; Su, Jianqiang; Ma, Yibing; Zhu, Yong-Guan

    2016-01-01

    Sewage sludge and manure are common soil amendments in crop production; however, their impact on the abundance and diversity of the antibiotic resistome in soil remains elusive. In this study, by using high-throughput sequencing and high-throughput quantitative PCR, the patterns of bacterial community and antibiotic resistance genes (ARGs) in a long-term field experiment were investigated to gain insights into these impacts. A total of 130 unique ARGs and 5 mobile genetic elements (MGEs) were detected and the long-term application of sewage sludge and chicken manure significantly increased the abundance and diversity of ARGs in the soil. Genes conferring resistance to beta-lactams, tetracyclines, and multiple drugs were dominant in the samples. Sewage sludge or chicken manure applications caused significant enrichment of 108 unique ARGs and MGEs with a maximum enrichment of up to 3845 folds for mexF. The enrichment of MGEs suggested that the application of sewage sludge or manure may accelerate the dissemination of ARGs in soil through horizontal gene transfer (HGT). Based on the co-occurrence pattern of ARGs subtypes revealed by network analysis, aacC, oprD and mphA-02, were proposed to be potential indicators for quantitative estimation of the co-occurring ARGs subtypes abundance by power functions. The application of sewage sludge and manure resulted in significant increase of bacterial diversity in soil, Proteobacteria, Acidobacteria, Actinobacteria and Chloroflexi were the dominant phyla (>10% in each sample). Five bacterial phyla (Chloroflexi, Planctomycetes, Firmicutes, Gemmatimonadetes and Bacteroidetes) were found to be significantly correlated with the ARGs in soil. Mantel test and variation partitioning analysis (VPA) suggested that bacterial community shifts, rather than MGEs, is the major driver shaping the antibiotic resistome. Additionally, the co-occurrence pattern between ARGs and microbial taxa revealed by network analysis indicated that four

  7. Abundance of antibiotic resistance genes in five municipal wastewater treatment plants in the Monastir Governorate, Tunisia.

    Science.gov (United States)

    Rafraf, Ikbel Denden; Lekunberri, Itziar; Sànchez-Melsió, Alexandre; Aouni, Mahjoub; Borrego, Carles M; Balcázar, José Luis

    2016-12-01

    Antimicrobial resistance is a growing and significant threat to global public health, requiring better understanding of the sources and mechanisms involved in its emergence and spread. We investigated the abundance of antibiotic resistance genes (ARGs) before and after treatment in five wastewater treatment plants (WWTPs) located in different areas of the Monastir Governorate (Tunisia). Three of these WWTPs (Frina, Sahline and Zaouiet) use a conventional activated sludge process as secondary treatment, whereas the WWTP located in Beni Hassen applies an ultraviolet disinfection step after the activated sludge process and the WWTP located in Moknine treats wastewater using naturally aerated lagoons as a secondary treatment process. The abundance of six ARGs (blaCTX-M, blaTEM, qnrA, qnrS, sul I and ermB) and the class 1 integron-integrase gene (intI1) were determined by quantitative PCR. All ARGs and the intI1 gene were detected in the wastewater samples, except the blaCTX-M gene, which was not detected in both influent and effluent samples from Sahline and Beni Hassen WWTPs, and the qnrS gene, which was not detected neither in the WWTP influent in Moknine nor in the WWTP effluent in Beni Hassen. Although the relative concentration of ARGs was generally found to be similar between samples collected before and after the wastewater treatment, the abundance of blaCTX-M, blaTEM, and qnrS genes was higher in the effluent of the Frina WWTP which, unlike other WWTPs, not only receives domestic or industrial sewage but also untreated hospital waste. To the best of our knowledge, this study quantified for the first time the abundance of ARGs in different Tunisian WWTPs, and the results agree with previous studies suggesting that conventional wastewater treatment does not efficiently reduce ARGs. Therefore, these findings could be useful to improve the design or operation of WWTPs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Metagenomic profiles and antibiotic resistance genes in gut microbiota of mice exposed to arsenic and iron.

    Science.gov (United States)

    Guo, Xuechao; Liu, Su; Wang, Zhu; Zhang, Xu-xiang; Li, Mei; Wu, Bing

    2014-10-01

    Iron (Fe) has been widely applied to treat arsenic (As)-contaminated water, and Fe could influence bioavailability and toxicity of As. However, little is known about the impact of As and/or Fe on gut microbiota, which plays important roles in host health. In this study, high-throughput sequencing and quantitative real time PCR were applied to analyze the impact of As and Fe on mouse gut microbiota. Co-exposure of As and Fe mitigated effects on microbial community to a certain extent. Correlation analysis showed the shifts in gut microbiota caused by As and/or Fe exposure might be important reason of changes in metabolic profiles of mouse. For antibiotic resistance genes (ARGs), co-exposure of As and Fe increased types and abundance of ARGs. But for high abundance ARGs, such as tetQ, tetO and tetM, co-exposure of As and Fe mitigated effects on their abundances compared to exposure to As and Fe alone. No obvious relationship between ARGs and mobile genetic elements were found. The changes in ARGs caused by metal exposure might be due to the alteration of gut microbial diversity. Our results show that changes of gut microbial community caused by As and/or Fe can influence host metabolisms and abundances of ARGs in gut, indicating that changes of gut microbiota should be considered during the risk assessment of As and/or Fe.

  9. Comparison of different disinfection processes in the effective removal of antibiotic-resistant bacteria and genes.

    Science.gov (United States)

    Oh, Junsik; Salcedo, Dennis Espineli; Medriano, Carl Angelo; Kim, Sungpyo

    2014-06-01

    This study compared three different disinfection processes (chlorination, E-beam, and ozone) and the efficacy of three oxidants (H2O2, S2O(-)8, and peroxymonosulfate (MPS)) in removing antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in a synthetic wastewater. More than 30 mg/L of chlorine was needed to remove over 90% of ARB and ARG. For the E-beam method, only 1 dose (kGy) was needed to remove ARB and ARG, and ozone could reduce ARB and ARG by more than 90% even at 3 mg/L ozone concentration. In the ozone process, CT values (concentration × time) were compared for ozone alone and combined with different catalysts based on the 2-log removal of ARB and ARG. Ozone treatment yielded a value of 31 and 33 (mg·min)/L for ARB and ARGs respectively. On the other hand, ozone with persulfate yielded 15.9 and 18.5 (mg·min)/L while ozone with monopersulfate yielded a value of 12 and 14.5 (mg·min)/L. This implies that the addition of these catalysts significantly reduces the contact time to achieve a 2-log removal, thus enhancing the process in terms of its kinetics.

  10. Effect of different biochars on antibiotic resistance genes and bacterial community during chicken manure composting.

    Science.gov (United States)

    Cui, Erping; Wu, Ying; Zuo, Yiru; Chen, Hong

    2016-03-01

    Rice straw biochar (RSB) and mushroom biochar (MB) were added to lab-scale chicken manure composting to evaluate their effects on the behaviors of antibiotic resistance genes (ARGs) and on total and bio-available heavy metals (Cu, Zn and As). The associated bacterial community was characterized by 16SrRNA high-throughput sequencing. The abundance of pathogenic bacteria was also calculated. At the end of the control composting experiment, the average removal rate of ARGs was 0.86 log units and the removal rate of pathogenic bacteria was 57.1%. MB addition resulted in a higher removal rate than that in the control composting experiment. However, RSB addition yielded opposite results, which may be due to the higher abundance of Erysipelotrichaceae, Lactobacillaceae, Family_XI_Incertae_Sedis (belonging to Firmicutes carrying and disseminating ARGs) and pathogenic bacteria carrying ARGs. Furthermore, the correlations between bio-available heavy metals and ARGs were more obvious than those between total heavy metals and ARGs.

  11. The Effect of Selective D- or Nα-Methyl Arginine Substitution on the Activity of the Proline-Rich Antimicrobial Peptide, Chex1-Arg20

    Science.gov (United States)

    Li, Wenyi; Sun, Zhe; O'Brien-Simpson, Neil M.; Otvos, Laszlo; Reynolds, Eric C.; Hossain, Mohammed A.; Separovic, Frances; Wade, John D.

    2017-01-01

    In vivo pharmacokinetics studies have shown that the proline-rich antimicrobial peptide, A3-APO, which is a discontinuous dimer of the peptide, Chex1-Arg20, undergoes degradation to small fragments at positions Pro6-Arg7 and Val19-Arg20. With the aim of minimizing or abolishing this degradation, a series of Chex1-Arg20 analogs were prepared via Fmoc/tBu solid phase peptide synthesis with D-arginine or, in some cases, peptide backbone Nα-methylated arginine, substitution at these sites. All the peptides were tested for antibacterial activity against the Gram-negative bacterium Klebsiella pneumoniae. The resulting activity of position-7 substitution of Chex1-Arg20 analogs showed that arginine-7 is a crucial residue for maintaining activity against K. pneumoniae. However, arginine-20 substitution had a much less deleterious effect on the antibacterial activity of the peptide. Moreover, none of these peptides displayed any cytotoxicity to HEK and H-4-II-E mammalian cells. These results will aid the development of more effective and stable PrAMPs via judicious amino acid substitutions. PMID:28154813

  12. Roles of distal arginine in activity and stability of Coprinus cinereus peroxidase elucidated by kinetic and NMR analysis of the Arg51Gln, -Asn, -Leu, and -Lys mutants.

    Science.gov (United States)

    Schiødt, Christine B; Veitch, Nigel C; Welinder, Karen G

    2007-02-01

    In heme peroxidases, a distal His residue plays an essential role in the initial two electron oxidation of resting state enzyme to compound I by hydrogen peroxide. A distal Arg residue assists in this process. The contributions of the charge, H-bonding capacity, size, and mobility of this Arg residue to Coprinus cinereus peroxidase (CIP) reactivity and stability have been examined by substituting Arg51 with Gln (retains H-bond donor at N epsilon position), Asn (small size, H-bond donor and acceptor), Leu (similar to Asn, but hydrophobic), and Lys (charge and H-bond donor, but at N zeta position). UV-visible spectroscopy was used to monitor pH-linked heme changes, compound I formation and reduction, fluoride binding, and thermostability. (1)H NMR spectroscopy enabled heme pocket differences in both resting and cyanide-ligated states of the enzymes to be evaluated and compared with wild-type CIP. We found that the H-bonding capacity of distal Arg is key to fast compound I formation and ligand binding to heme, whereas charge is important for lowering the pK(a) of distal His and for the binding and stabilisation of anionic ligands at heme iron. The properties of the distal Arg residue in CIP, cytochrome c peroxidase (CCP) and horseradish peroxidase (HRP) differ significantly in their pH induced transitions and dynamics.

  13. The effect of selective D- or N(alpha)-methyl arginine substitution on the activity of the proline-rich antimicrobial peptide, Chex1-Arg20.

    Science.gov (United States)

    Li, Wenyi; Sun, Zhe; O'Brien-Simpson, Neil M.; Otvos, Laszlo; Reynolds, Eric C.; Hossain, Mohammed A.; Separovic, Frances; Wade, John D.

    2017-01-01

    In vivo pharmacokinetics studies have shown that the proline-rich antimicrobial peptide, A3-APO, which is a discontinuous dimer of the peptide, Chex1-Arg20, undergoes degradation to small fragments at positions Pro6-Arg7 and Val19-Arg20. With the aim of minimizing or abolishing this degradation, a series of Chex1-Arg20 analogues were prepared via Fmoc/tBu solid phase peptide synthesis with D-arginine or, in some cases, peptide backbone N-methylated arginine, substitution at these sites. All the peptides were tested for antibacterial activity against the Gram-negative bacterium Klebsiella pneumoniae. The resulting activity of position-7 substitution of Chex1-Arg20 analogues showed that arginine-7 is a crucial residue for maintaining activity against K. pneumoniae. However, arginine-20 substitution had a much less deleterious effect on the antibacterial activity of the peptide. Moreover, none of these peptides displayed any cytotoxicity to HEK and H-4-II-E mammalian cells. These results will aid the development of more effective and stable PrAMPs via judicious amino acid substitutions.

  14. Recurrent FXYD2 p.Gly41Arg mutation in patients with isolated dominant hypomagnesaemia

    NARCIS (Netherlands)

    de Baaij, Jeroen H. F.; Dorresteijn, Eiske M.; Hennekam, Eric A. M.; Kamsteeg, Erik-Jan; Meijer, Rowdy; Dahan, Karin; Muller, Michelle; van den Dorpel, Marinus A.; Bindels, Rene J. M.; Hoenderop, Joost G. J.; Devuyst, Olivier; Knoers, Nine V. A. M.

    2015-01-01

    Background. Magnesium (Mg2+) is an essential ion for cell growth, neuroplasticity and muscle contraction. Blood Mg2+ levels Methods. Here, two families with hypomagnesaemia and hypocalciuria were screened for mutations in the FXYD2 gene. Moreover, the patients were clinically and genetically charact

  15. Effects of biochar on reducing the abundance of oxytetracycline, antibiotic resistance genes, and human pathogenic bacteria in soil and lettuce.

    Science.gov (United States)

    Duan, Manli; Li, Haichao; Gu, Jie; Tuo, Xiaxia; Sun, Wei; Qian, Xun; Wang, Xiaojuan

    2017-05-01

    Antibiotics and antibiotic resistance genes (ARGs) in soil can affect human health via the food chain. Biochar is a soil amendment but its impacts on ARGs and the microbial communities associated with soil and vegetables are unclear. Therefore, we established three lettuce pot culture experiments, i.e., O300: 300 mg/kg oxytetracycline (OTC), BO300: 300 mg/kg OTC + 2% biochar, and a control without OTC or biochar. We found that under BO300, the relative abundances of ARGs were reduced by 51.8%, 43.4%, and 44.1% in lettuce leaves, roots, and soil, respectively, compared with O300. intI1 was highly abundant in soil and lettuce, and it co-occurred with some ARGs (tetW, ermF, and sul1). Redundancy analysis and network analysis indicated that the bacterial community succession was the main mechanism that affected the variations in ARGs and intI1. The reduction of Firmicutes due to the biochar treatment of soil and lettuce was the main factor responsible for the removal of tetracycline resistance genes in leaves. Biochar application led to the disappearance of human pathogenic bacteria (HPB), which was significantly correlated with the abundances of ermF and ermX. In summary, biochar is an effective farmland amendment for reducing the abundances of antibiotics, ARGs, and HPB in order to ensure the safety of vegetables and protect human health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Prevalence of antibiotic resistance genes and bacterial community composition in a river influenced by a wastewater treatment plant.

    Directory of Open Access Journals (Sweden)

    Elisabet Marti

    Full Text Available Antibiotic resistance represents a global health problem, requiring better understanding of the ecology of antibiotic resistance genes (ARGs, their selection and their spread in the environment. Antibiotics are constantly released to the environment through wastewater treatment plant (WWTP effluents. We investigated, therefore, the effect of these discharges on the prevalence of ARGs and bacterial community composition in biofilm and sediment samples of a receiving river. We used culture-independent approaches such as quantitative PCR to determine the prevalence of eleven ARGs and 16S rRNA gene-based pyrosequencing to examine the composition of bacterial communities. Concentration of antibiotics in WWTP influent and effluent were also determined. ARGs such as qnrS, bla TEM, bla CTX-M, bla SHV, erm(B, sul(I, sul(II, tet(O and tet(W were detected in all biofilm and sediment samples analyzed. Moreover, we observed a significant increase in the relative abundance of ARGs in biofilm samples collected downstream of the WWTP discharge. We also found significant differences with respect to community structure and composition between upstream and downstream samples. Therefore, our results indicate that WWTP discharges may contribute to the spread of ARGs into the environment and may also impact on the bacterial communities of the receiving river.

  17. Metagenomic profiling of antibiotic resistance genes and mobile genetic elements in a tannery wastewater treatment plant.

    Directory of Open Access Journals (Sweden)

    Zhu Wang

    Full Text Available Antibiotics are often used to prevent sickness and improve production in animal agriculture, and the residues in animal bodies may enter tannery wastewater during leather production. This study aimed to use Illumina high-throughput sequencing to investigate the occurrence, diversity and abundance of antibiotic resistance genes (ARGs and mobile genetic elements (MGEs in aerobic and anaerobic sludge of a full-scale tannery wastewater treatment plant (WWTP. Metagenomic analysis showed that Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria dominated in the WWTP, but the relative abundance of archaea in anaerobic sludge was higher than in aerobic sludge. Sequencing reads from aerobic and anaerobic sludge revealed differences in the abundance of functional genes between both microbial communities. Genes coding for antibiotic resistance were identified in both communities. BLAST analysis against Antibiotic Resistance Genes Database (ARDB further revealed that aerobic and anaerobic sludge contained various ARGs with high abundance, among which sulfonamide resistance gene sul1 had the highest abundance, occupying over 20% of the total ARGs reads. Tetracycline resistance genes (tet were highly rich in the anaerobic sludge, among which tet33 had the highest abundance, but was absent in aerobic sludge. Over 70 types of insertion sequences were detected in each sludge sample, and class 1 integrase genes were prevalent in the WWTP. The results highlighted prevalence of ARGs and MGEs in tannery WWTPs, which may deserve more public health concerns.

  18. Arc/Arg3.1 mRNA global expression patterns elicited by memory recall in cerebral cortex differ for remote versus recent spatial memories

    Directory of Open Access Journals (Sweden)

    Pavel A Gusev

    2010-05-01

    Full Text Available The neocortex plays a critical role in the gradual formation and storage of remote declarative memories. Because the circuitry mechanisms of systems-level consolidation are not well understood, the precise cortical sites for memory storage and the nature of enduring memory correlates (mnemonic plasticity are largely unknown. Detailed maps of neuronal activity underlying recent and remote memory recall highlight brain regions that participate in systems consolidation and constitute putative storage sites, and thus may facilitate detection of mnemonic plasticity. To localize cortical regions involved in the recall of a spatial memory task, we trained rats in a water maze and then mapped mRNA expression patterns of a neuronal activity marker Arc/Arg3.1 (Arc upon recall of recent (24 hours after training or remote (one month after training memories and compared them with swimming and naive controls. Arc gene expression was significantly more robust 24 hours after training compared to one month after training. Arc expression diminished in the parietal, cingulate and visual areas, but select segments in the prefrontal, retrosplenial, somatosensory and motor cortical showed similar robust increases in the Arc expression. When Arc expression was compared across select segments of sensory, motor and associative regions within recent and remote memory groups, the overall magnitude and cortical laminar patterns of task-specific Arc expression were similar (stereotypical. Arc mRNA fractions expressed in the upper cortical layers (2/3, 4 increased after both recent and remote recall, while layer 6 fractions decreased only after the recent recall. The data suggest that robust recall of remote memory requires an overall smaller increase in neuronal activity within fewer cortical segments. This activity trend highlights the difficulty in detecting the storage sites and plasticity underlying remote memory. Application of the Arc maps may ameliorate this

  19. How contemporary human reproductive behaviors influence the role of fertility-related genes: the example of the p53 gene.

    Directory of Open Access Journals (Sweden)

    Rosa Maria Corbo

    Full Text Available Studies on human fertility genes have identified numerous risk/protective alleles involved in the occurrence of reproductive system diseases causing infertility or subfertility. Investigations we carried out in populations at natural fertility seem to suggest that the clinical relevance that some fertility genes are now acquiring depends on their interaction with contemporary reproductive behaviors (birth control, delayed childbearing, and spacing birth order, among others. In recent years, a new physiological role in human fertility regulation has emerged for the tumor- suppressor p53 gene (P53, and the P53 Arg72Pro polymorphism has been associated with recurrent implantation failure in humans. To lend support to our previous observations, we examined the impact of Arg72Pro polymorphism on fertility in two samples of Italian women not selected for impaired fertility but collected from populations with different (premodern and modern reproductive behaviors. Among the women at near-natural fertility (n = 98, the P53 genotypes were not associated with different reproductive efficiency, whereas among those with modern reproductive behaviors (n = 68, the P53 genotypes were associated with different mean numbers of children [Pro/Pro = 0.75Arg = 1.7<Arg/Arg = 2, (p = 0.056] and a significant negative relationship between the number of children and P53 Pro allele frequencies (p = 0.028 was observed. These results are consistent with those of clinical studies reporting an association between the P53 Pro allele and recurrent implantation failure. By combining these findings with previous ones, we suggest here that some common variants of fertility genes may have become "detrimental" following exposure to modern reproductive patterns and might therefore be associated with reduced reproductive success. Set within an evolutionary framework, this change could lead to the selection of a set of gene variants fitter to current reproductive behaviors as the

  20. 大位阻氨基酸Fmoc-Arg(Pbf)-OH与Rink Amide-AM树脂的高效缩合%Highly efficient condensation of sterically hindered amino acid fmoc-arg(Pbf)-OH and rink amide-AM resin

    Institute of Scientific and Technical Information of China (English)

    朱亮亮; 绳则翠; 周成; 祝社民; 陈英文; 沈树宝

    2012-01-01

    The coupling reactions of Fmoc-Arg( Pbf) -OH and Rink Amide-AM Resin with symmetrical anhydride method, active ester method and 2,6-dichlorobenoyl chloride (DCB) method, respectively, were investigated in a self-designed reactor which congregated the stirring,filtration,and bubbling function together. The effects of reaction strategy, solvent system, reaction time, molar ratio of reactants and stirring method on the yield of condensation reaction were performed. The results indicate that the DIC/HOBt/DMAP strategy is the best method. The optimal reaction conditions are shown as follows: 3 : 1 of molar ratio of the reactants, 3 h of reaction time and DMA/DCM ( 1 : 1, V/ V) as a solvent using nitrogen-assisted magnetic stir system. The highest yield of the condensation reaction is 93% .%采用集自动搅拌、过滤、鼓泡等多重功能于一体的自制多肽固相合成反应器,以对称酸酐法、活化酯法、2,6-二氯苯甲酰氯(DCB)法研究了大位阻氨基酸Fmoc-Arg (Pbf)-OH与Rink Amide-AM树脂的连接反应工艺.探讨了催化体系、溶剂体系、反应时间、反应物配比以及搅拌方式对合成Fmoc-Arg(Pbf)-Rink Amide-AM树脂反应的影响.结果表明,采用活化酯法(DIC/HOBt/DMAP)时连接率最高,最佳反应条件为:在采用N2辅助磁力拌系统,以体积比为1∶1的DMA/DCM为反应溶剂,氨基酸与树脂物质的量的比为3∶1,反应时间为3h时,连接率高达93%.

  1. Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer

    Directory of Open Access Journals (Sweden)

    Christian Johannes Hendrik Von Wintersdorff

    2016-02-01

    Full Text Available The emergence and spread of antibiotic resistance among pathogenic bacteria has been a rising problem for public health in recent decades. It is becoming increasingly recognized that not only antibiotic resistance genes (ARGs encountered in clinical pathogens are of relevance, but rather, all pathogenic, commensal as well as environmental bacteria – and also mobile genetic elements and bacteriophages – form a reservoir of ARGs (the resistome from which pathogenic bacteria can acquire resistance via horizontal gene transfer (HGT. HGT has caused antibiotic resistance to spread from commensal and environmental species to pathogenic ones, as has been shown for some clinically important ARGs. Of the three canonical mechanisms of HGT, conjugation is thought to have the greatest influence on the dissemination of ARGs. While transformation and transduction are deemed less important, recent discoveries suggest their role may be larger than previously thought. Understanding the extent of the resistome and how its mobilization to pathogenic bacteria takes place is essential for efforts to control the dissemination of these genes. Here, we will discuss the concept of the resistome, provide examples of HGT of clinically relevant ARGs and present an overview of the current knowledge of the contributions the various HGT mechanisms make to the spread of antibiotic resistance.

  2. The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

    Energy Technology Data Exchange (ETDEWEB)

    Al-Saaidi, Rasha [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Rasmussen, Torsten B. [Department of Cardiology, Aarhus University Hospital, Aarhus (Denmark); Palmfeldt, Johan [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark); Nissen, Peter H. [Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus (Denmark); Beqqali, Abdelaziz [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Hansen, Jakob [Department of Forensic Medicine, Bioanalytical Unit, University of Aarhus (Denmark); Pinto, Yigal M. [Heart Failure Research Center, Academic Medical Center, Amsterdam (Netherlands); Boesen, Thomas [Department of Molecular Biology and Genetics, University of Aarhus (Denmark); Mogensen, Jens [Department of Cardiology, Odense University Hospital, Odense (Denmark); Bross, Peter, E-mail: peter.bross@ki.au.dk [Research Unit for Molecular Medicine, Aarhus University and Aarhus University Hospital, Aarhus (Denmark)

    2013-11-15

    Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant negative effects have been proposed as disease mechanism for premature termination codon (PTC) mutations in LMNA. These mechanisms however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR and sequencing of these PCR products indicated that transcripts from the mutant allele were degraded by the nonsense-mediated mRNA decay (NMD) mechanism. The fact that no truncated mutant protein was detectable in western blot (WB) analysis strengthens the notion that the mutant transcript is efficiently degraded. Furthermore, WB analysis showed that the expression of lamin C protein was reduced by the expected approximately 50%. Clearly decreased lamin A and lamin C levels were also observed by immunofluorescence microscopy analysis. However, results from both WB and nano-liquid chromatography/mass spectrometry demonstrated that the levels of lamin A protein were more reduced suggesting an effect on expression of lamin A from the wild type allele. PCR analysis of the ratio of lamin A to lamin C transcripts showed unchanged relative amounts of lamin A transcript suggesting that the effect on the wild type allele was operative at the protein level. Immunofluorescence microscopy analysis showed no abnormal nuclear morphology of patient fibroblast cells. Based on these data, we propose that

  3. Mutations of androgen receptor gene in Brazilian patients with male pseudohermaphroditism

    Directory of Open Access Journals (Sweden)

    D.F. Cabral

    1998-06-01

    Full Text Available We describe the identification of point mutations in the androgen receptor gene in five Brazilian patients with female assignment and behavior. The eight exons of the gene were amplified by the polymerase chain reaction (PCR and analyzed for single-strand conformation polymorphism (SSCP to detect the mutations. Direct sequencing of the mutant PCR products demonstrated single transitions in three of these cases: G®A in case 1, within exon C, changing codon 615 from Arg to His; G®A in case 2, within exon E, changing codon 752 from Arg to Gln, and C®T in case 3, within exon B, but without amino acid change.

  4. MC1R gene polymorphism affects skin color and phenotypic features related to sun sensitivity in a population of French adult women.

    Science.gov (United States)

    Latreille, Julie; Ezzedine, Khaled; Elfakir, Anissa; Ambroisine, Laurence; Gardinier, Sophie; Galan, Pilar; Hercberg, Serge; Gruber, Florian; Rees, Jonathan; Tschachler, Erwin; Guinot, Christiane

    2009-01-01

    The melanocortin-1 receptor (MC1R) gene is known to play a major role in skin and hair pigmentation and to be highly polymorphic in Caucasians. This study was performed to investigate the relationships between MC1R gene polymorphisms and skin color in a large sample of French middle-aged Caucasian women. The codons 60 to 265 and the codon 294 of the MC1R gene were sequenced in 488 women. The skin color was measured on the inner side of the forearm using a spectrophotometric instrument. Fifteen variants were identified: Arg151Cys, Arg160Trp, Arg142His, Asp294His, Ile155Thr, Asp84Glu, Val60Leu, Val92Met, Arg163Gln, Ser83Pro, Thr95Met, Pro256Ser, Val265Ile, Ala166Ala and Gln233Gln. Women carrying Arg151Cys, Asp294His, Arg160Trp and Asp84Glu variants had a significantly higher reflectance in the red region, which indicates a lower level of functional melanin. This association was the most pronounced for women carrying Asp84Glu. In contrast, no significant difference was observed for other variants. Moreover, associations between MC1R polymorphisms and the risks of experiencing sunburn and of having freckles were found independently of skin color. Our findings support the hypothesis that MC1R polymorphisms do not necessarily alter the skin color but should sensitize the skin to UV-induced DNA damage.

  5. La técnica de impregnación argéntica de Golgi. Conmemoración del centenario del premio nobel de Medicina (1906 compartido por Camillo Golgi y Santiago Ramón y Cajal

    Directory of Open Access Journals (Sweden)

    Orlando Torres-Fernández

    2006-12-01

    Full Text Available La técnica de Golgi es un sencillo procedimiento histológico que revela la morfología neuronal completa en tres dimensiones. Este método se fundamenta en la formación de depósitos opacos intracelulares de cromato argéntico, producto de la reacción entre el bicromato de potasio y el nitrato de plata (reacción negra. Camillo Golgi, su descubridor, y Santiago Ramón y Cajal, su principal exponente, recibieron el premio nobel de Medicina y Fisiología en 1906 por su contribución al conocimiento de la estructura del sistema nervioso. Gran parte de sus logros se obtuvieron a través de la aplicación del método de impregnación argéntica. Sin embargo, Golgi y Cajal tenían interpretaciones diferentes sobre la estructura del tejido nervioso. Golgi era defensor de la teoría reticular, la cual proponía que el sistema nervioso estaba conformado por una red de células fusionadas a través de los axones a manera de un sincitio. Por el contrario, la doctrina neuronal, defendida por Cajal, sostenía que las neuronas eran células independientes. También se debe a Golgi y su reazione nera el descubrimiento del organelo celular conocido como ‘aparato de Golgi'. La microscopía electrónica confirmó los postulados de la doctrina neuronal, así como la existencia del complejo de Golgi, y contribuyó al resurgimiento de la técnica de impregnación argéntica. Aunque existen métodos modernos de tinción intracelular que revelan imágenes excelentes de la morfología neuronal, la técnica de Golgi se mantiene vigente por ser un método más práctico y menos costoso para el estudio de la morfología normal y patológica de las neuronas.

  6. Metagenomic Analysis of Antibiotic Resistance Genes in Dairy Cow Feces following Therapeutic Administration of Third Generation Cephalosporin.

    Directory of Open Access Journals (Sweden)

    Lindsey Chambers

    Full Text Available Although dairy manure is widely applied to land, it is relatively understudied compared to other livestock as a potential source of antibiotic resistance genes (ARGs to the environment and ultimately to human pathogens. Ceftiofur, the most widely used antibiotic used in U.S. dairy cows, is a 3rd generation cephalosporin, a critically important class of antibiotics to human health. The objective of this study was to evaluate the effect of typical ceftiofur antibiotic treatment on the prevalence of ARGs in the fecal microbiome of dairy cows using a metagenomics approach. β-lactam ARGs were found to be elevated in feces from Holstein cows administered ceftiofur (n = 3 relative to control cows (n = 3. However, total numbers of ARGs across all classes were not measurably affected by ceftiofur treatment, likely because of dominance of unaffected tetracycline ARGs in the metagenomics libraries. Functional analysis via MG-RAST further revealed that ceftiofur treatment resulted in increases in gene sequences associated with "phages, prophages, transposable elements, and plasmids", suggesting that this treatment also enriched the ability to horizontally transfer ARGs. Additional functional shifts were noted with ceftiofur treatment (e.g., increase in genes associated with stress, chemotaxis, and resistance to toxic compounds; decrease in genes associated with metabolism of aromatic compounds and cell division and cell cycle, along with measureable taxonomic shifts (increase in Bacterioidia and decrease in Actinobacteria. This study demonstrates that ceftiofur has a broad, measureable and immediate effect on the cow fecal metagenome. Given the importance of 3rd generation cephalospirins to human medicine, their continued use in dairy cattle should be carefully considered and waste treatment strategies to slow ARG dissemination from dairy cattle manure should be explored.

  7. Genotyping and meta-analysis of KIF6 Trp719Arg polymorphism in South Indian Coronary Artery Disease patients: A case–control study

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    Durairajpandian Vishnuprabu

    2015-09-01

    Full Text Available The KIF6 719Arg allele is an interesting genomic variant widely screened in various populations and is reported to be associated with the risk of Coronary Artery Disease (CAD and statin treatment outcome. Recent population based clinical studies and large-scale meta-analyses pondered over the role of 719Arg variant in CAD risk and treatment response. We screened the KIF6 Trp719Arg polymorphism (rs20455 in south Indian CAD patients in a case–control approach. A total of 1042 samples (510 CAD patients and 532 controls were screened for the KIF6 Trp719Arg SNP by TaqMan SNP genotyping assay, followed by meta-analysis of the genotype data of non-Europeans reports. The 719Arg risk genotype (GG was observed in 29.6% of CAD cases and in 30.1% of controls with an odds ratio (OR of 1.07 (95% CI: 0.76–1.50, p value = 0.709. No significant difference in the genotype frequency was observed between CAD and controls in both dominant model (AG + GG vs AA and allelic model (719Arg vs 719Trp with an OR of 1.11 (p = 0.491 and 1.03 (p = 0.767, respectively. The covariate analysis indicated that smoking & alcohol consumption increased the risk for MI among CAD patients. Meta-analysis showed that the KIF6 719Arg allele is not associated with CAD risk in both fixed effect (p = 0.515, OR = 1.023, 95% CI = 0.956–1.094 and random effect (p = 0.547, OR = 1.022, 95% CI = 0.953–1.096. The symmetrical shape of the Egger's funnel plots revealed that there is no publication bias. These results suggest that there is no association of KIF6 719Arg allele with CAD risk in South Indian population and the meta-analysis confirms the same among non-European population.

  8. A Comprehensive Insight into Tetracycline Resistant Bacteria and Antibiotic Resistance Genes in Activated Sludge Using Next-Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Kailong Huang

    2014-06-01

    Full Text Available In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB and antibiotic resistance genes (ARGs in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP sludge.

  9. Physiological and molecular responses to variation of light intensity in rubber Tree (Hevea brasiliensis Muell. Arg..

    Directory of Open Access Journals (Sweden)

    Li-feng Wang

    Full Text Available Light is one of most important factors to plants because it is necessary for photosynthesis. In this study, physiological and gene expression analyses under different light intensities were performed in the seedlings of rubber tree (Hevea brasiliensis clone GT1. When light intensity increased from 20 to 1000 µmol m(-2 s(-1, there was no effect on the maximal quantum yield of photosystem II (PSII photochemistry (Fv/Fm, indicating that high light intensity did not damage the structure and function of PSII reaction center. However, the effective photochemical quantum yield of PSII (Y(II, photochemical quenching coefficient (qP, electron transfer rate (ETR, and coefficient of photochemical fluorescence quenching assuming interconnected PSII antennae (qL were increased significantly as the light intensity increased, reached a maximum at 200 µmol m(-2 s(-1, but decreased from 400 µmol m(-2 s(-1. These results suggested that the PSII photochemistry showed an optimum performance at 200 µmol m(-2 s(-1 light intensity. The chlorophyll content was increased along with the increase of light intensity when it was no more than 400 µmol m(-2 s(-1. Since increasing light intensity caused significant increase in H2O2 content and decreases in the per unit activity of antioxidant enzymes SOD and POD, but the malondialdehyde (MDA content was preserved at a low level even under high light intensity of 1000 µmol m(-2 s(-1, suggesting that high light irradiation did not induce membrane lipid peroxidation in rubber tree. Moreover, expressions of antioxidant-related genes were significantly up-regulated with the increase of light intensity. They reached the maximum expression at 400 µmol m(-2 s(-1, but decreased at 1000 µmol m(-2 s(-1. In conclusion, rubber tree could endure strong light irradiation via a specific mechanism. Adaptation to high light intensity is a complex process by regulating antioxidant enzymes activities, chloroplast formation, and related

  10. COMPARATIVE STUDY OF TOURIST TRAFFIC AT THE CITY, COUNTY AND HOUSE IN CÂMPULUNG MUSCEL ARGES

    Directory of Open Access Journals (Sweden)

    Adelaida Cristina HONTUŞ

    2013-01-01

    Full Text Available This paper is based on a comparative analysis of tourism demand and supply and the development of mountain tourism tendinţelorde plannaţional and internationally, the degree of capitalization of the mountain tourism in Romania, focusing on assessment of tourism in the tourist resort Campulung Muscel County Arges. The objective of this study consists of a comparative analysis of tourist traffic at the county level tourist resort and tourist board level. To perform this study we used a series of statistical data provided by the representatives of the City of Delhi Muscel on tourism and tourist traffic statistics on the county level and at the boarding house.

  11. The BRCA1 c. 5096G>A p.Arg1699Gln (R1699Q) intermediate risk variant

    DEFF Research Database (Denmark)

    Moghadasi, Setareh; Meeks, Huong D.; Vreeswijk, Maaike Pg

    2017-01-01

    BACKGROUND: We previously showed that the BRCA1 variant c.5096G>A p.Arg1699Gln (R1699Q) was associated with an intermediate risk of breast cancer (BC) and ovarian cancer (OC). This study aimed to assess these cancer risks for R1699Q carriers in a larger cohort, including follow-up of previously...... studied families, to further define cancer risks and to propose adjusted clinical management of female BRCA1*R1699Q carriers. METHODS: Data were collected from 129 BRCA1*R1699Q families ascertained internationally by ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles...... risk for BC and OC. Breast surveillance for female carriers based on mammogram annually from age 40 is advised. Bilateral salpingo-oophorectomy should be considered based on family history....

  12. Ornithological researches on the Goleşti Dam Lake (Argeş county, Romania during 2003 - 2010

    Directory of Open Access Journals (Sweden)

    Denisa CONETE

    2012-05-01

    Full Text Available 199 bird species were observed in the Goleşti Dam Lake, from the middle hydrographical basin of the Argeş River, during 2003 – 2010 (minimum – 64 in January and maximum – 141 in April. Their distribution regarding the constancy, dominancy and Dzuba index of ecological signification were considered. There are two eudominant species (Anas platyrhynchos and Aythya ferina and two dominant species (Aythya fuligula and Larus ridibundus. The variation in the number of individuals during the year is strongly determined by the temperature variation that leads to the diminishing or increasing of the food resources. In winter, when the temperatures were low in the north (and the waters froze, the birds arrived in great number in our area but only a few of them remained in the area for breeding.

  13. Evaluation of analgesic and anti-inflammatory effects of aerial parts of Breynia rhamnoides Muell.-Arg.

    Directory of Open Access Journals (Sweden)

    Shadiya C. K.

    2015-09-01

    Full Text Available The plant Breynia rhamnoides Muell. Arg (family-Phyllanthaceae/Euphorbiaceae was reported to have numerous potent constituents and the same plant was used for many traditional medicines. Phytochemical analysis of ethanolic extracts of Breynia rhamnoides revealed the presence of many active compounds such as flavonoids, glycosides, phenolic compounds, terpenoids, steroids and saponins. Present work describes the extraction and evaluation of analgesic and anti-inflammatory activities of aerial part extract of Breynia rhamnoides. Acute toxicity studies were performed as per OECD-423 guidelines. Toxicity signs and symptoms were not observed. Anti-inflammatory activity was evaluated by carrageenan-induced paw edema model and analgesic activity by Eddy’s hot plate method and Acetic acid induced writhing method in Wistar albino rats. The extract exhibited significant anti- inflammatory and peripheral analgesic activity.

  14. Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil.

    Science.gov (United States)

    Mattevi, V S; Zembrzuski, V M; Hutz, M H

    2002-09-01

    To investigate associations of polymorphisms in the LEP, LEPR and NPY genes with obesity-related traits in a Brazilian population of European descent. A total of 183 women and 153 men (mean body mass index (BMI), 26.1+/-4.8 kg/m(2)) were genotyped using the PCR-RFLP procedure for the LEP A19G, LEPR Gln223Arg, LEPR PRO1019pro and NPY Leu7Pro polymorphisms. Frequencies were compared among normal-weight and overweight plus obese groups with chi-square tests, mean BMI and waist circumference were compared among genotypes by t-tests and analysis of variance. The genotype and allele frequencies of the LEPR Gln223Arg polymorphism were significantly different between normal-weight and overweight plus obese groups (P=0.013 and 0.009, respectively). Although there was no difference in the mean adjusted BMI among the three LEPRGln223Arg genotypes, a trend was observed for Arg/Arg individuals to have a higher mean BMI compared to Gln/Gln homozygotes, with heterozygote individuals presenting intermediate mean BMI between the two homozygote groups (ANOVA, P=0.063). However, in non-smokers, the LEPR Gln223Arg polymorphism showed a highly significant effect over BMI (P=0.009). When the analysis was restricted to premenopausal women, a highly significant effect of NPY was observed. Women bearing the Pro variant presented a lower BMI than wild-type homozygotes (P=0.001). Our findings suggest that genetic variability in the leptin receptor and neuropeptide Y genes is implicated in body weight regulation, the LEPR Gln223Arg variant being associated with a BMI increase in this Caucasian population, especially in non-smokers, while the NPY Leu7Pro polymorphism was associated with BMI reduction in premenopausal women.

  15. Living with high putrescine: expression of ornithine and arginine biosynthetic pathway genes in high and low putrescine producing poplar cells.

    Science.gov (United States)

    Page, Andrew F; Minocha, Rakesh; Minocha, Subhash C

    2012-01-01

    Arginine (Arg) and ornithine (Orn), both derived from glutamate (Glu), are the primary substrates for polyamine (PA) biosynthesis, and also play important roles as substrates and intermediates of overall N metabolism in plants. Their cellular homeostasis is subject to multiple levels of regulation. Using reverse transcription quantitative PCR (RT-qPCR), we studied changes in the expression of all genes of the Orn/Arg biosynthetic pathway in response to up-regulation [via transgenic expression of mouse Orn decarboxylase (mODC)] of PA biosynthesis in poplar (Populus nigra × maximowiczii) cells grown in culture. Cloning and sequencing of poplar genes involved in the Orn/Arg biosynthetic pathway showed that they have high homology with similar genes in other plants. The expression of the genes of Orn, Arg and PA biosynthetic pathway fell into two hierarchical clusters; expression of one did not change in response to high putrescine, while members of the other cluster showed a shift in expression pattern during the 7-day culture cycle. Gene expression of branch point enzymes (N-acetyl-Glu synthase, Orn aminotransferase, Arg decarboxylase, and spermidine synthase) in the sub-pathways, constituted a separate cluster from those involved in intermediary reactions of the pathway (N-acetyl-Glu kinase, N-acetyl-Glu-5-P reductase, N-acetyl-Orn aminotransferase, N (2)-acetylOrn:N-acetyl-Glu acetyltransferase, N (2)-acetyl-Orn deacetylase, Orn transcarbamylase, argininosuccinate synthase, carbamoylphosphate synthetase, argininosuccinate lyase, S-adenosylmethionine decarboxylase, spermine synthase). We postulate that expression of all genes of the Glu-Orn-Arg pathway is constitutively coordinated and is not influenced by the increase in flux rate through this pathway in response to increased utilization of Orn by mODC; thus the pathway involves mostly biochemical regulation rather than changes in gene expression. We further suggest that Orn itself plays a major role in the

  16. Ophthalmic manifestations in a Chinese family with familial amyloid polyneuropathy due to a TTR Gly83Arg mutation.

    Science.gov (United States)

    Liu, T; Zhang, B; Jin, X; Wang, W; Lee, J; Li, J; Yuan, H; Cheng, X

    2014-01-01

    To describe the characteristic ophthalmic phenotypes of a large Chinese family with familial amyloid polyneuropathy due to a missense mutation in transthyretin (TTR) (c.307 C>G). Twenty-seven individuals (12 affected, 15 unaffected) from a five-generation Chinese family underwent general medical examination and comprehensive ophthalmic examination, including best correct visual acuity, intraocular pressure measurements, Schirmer test, slitlamp examination, fundoscopy, and ocular ultrasonography. Histological examination of vitreous biopsies using Congo red staining and immunohistochemistry was performed. Cardiovascular magnetic resonance (CMR), electrocardiogram, and echocardiogram were used to evaluate cardiac amyloidosis. Electromyography was used to evaluate nerve function. All four exons of TTR were amplified by PCR, sequenced using a Bigdye terminator v3.1 cycle sequencing kit and analyzed on an ABI 3700XL Genetic Analyzer. All 12 affected individuals in the family had ocular manifestations, including severe vitreous opacities, secondary glaucoma, xerophthalmia, dyscoria, and attenuated retinal arteries. Congo red staining demonstrated amyloid deposits in the vitreous, and immunohistochemical staining confirmed the deposition of TTR proteins in the vitreous. Twelve individuals had polyneuropathy, and electromyography detected functional damage in peripheral nerves. One individual was diagnosed with cardiac amyloidosis by CMR. Direct sequencing revealed the heterozygous missense mutation in TTR (c.307 C>G p.Gly83Arg) in all 12 affected individuals. The mutation co-segregated with the disease phenotype and was absent in 100 normal controls. Vitreous opacity is very common in patients with the TTR Gly83Arg mutation; other clinical characteristics associated with the mutation include polyneuropathy and cardiac amyloidosis.

  17. Housefly Larva Vermicomposting Efficiently Attenuates Antibiotic Resistance Genes in Swine Manure, with Concomitant Bacterial Population Changes.

    Science.gov (United States)

    Wang, Hang; Li, Hongyi; Gilbert, Jack A; Li, Haibo; Wu, Longhua; Liu, Meng; Wang, Liling; Zhou, Qiansheng; Yuan, Junxiang; Zhang, Zhijian

    2015-11-01

    Manure from swine treated with antimicrobials as feed additives is a major source for the expansion of the antibiotic resistance gene (ARG) reservoir in the environment. Vermicomposting via housefly larvae (Musca domestica) can be efficiently used to treat manure and regenerate biofertilizer, but few studies have investigated its effect on ARG attenuation. Here, we tracked the abundances of 9 ARGs and the composition and structure of the bacterial communities in manure samples across 6 days of full-scale manure vermicomposting. On day 6, the abundances of genes encoding tetracycline resistance [tet(M), tet(O), tet(Q), and tet(W)] were reduced (P biofertilizer in agroecosystems. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  18. In dogs we trust? Intersubjectivity, response-able relations, and the making of mine detector dogs.

    Science.gov (United States)

    Kirk, Robert G W

    2014-01-01

    The utility of the dog as a mine detector has divided the mine clearance community since dogs were first used for this purpose during the Second World War. This paper adopts a historical perspective to investigate how, why, and to what consequence, the use of minedogs remains contested despite decades of research into their abilities. It explores the changing factors that have made it possible to think that dogs could, or could not, serve as reliable detectors of landmines over time. Beginning with an analysis of the wartime context that shaped the creation of minedogs, the paper then examines two contemporaneous investigations undertaken in the 1950s. The first, a British investigation pursued by the anatomist Solly Zuckerman, concluded that dogs could never be the mine hunter's best friend. The second, an American study led by the parapsychologist J. B. Rhine, suggested dogs were potentially useful for mine clearance. Drawing on literature from science studies and the emerging subdiscipline of "animal studies," it is argued that cross-species intersubjectivity played a significant role in determining these different positions. The conceptual landscapes of Zuckerman and Rhine's disciplinary backgrounds are shown to have produced distinct approaches to managing cross-species relations, thus explaining how diverse opinions on minedog can coexist. In conclusion, it is shown that the way one structures relationships between humans and animals has profound impact on the knowledge and labor subsequently produced, a process that cannot be separated from ethical consequence.

  19. Use of commercial organic fertilizer increases the abundance of antibiotic resistance genes and antibiotics in soil.

    Science.gov (United States)

    Zhou, Xue; Qiao, Min; Wang, Feng-Hua; Zhu, Yong-Guan

    2017-01-01

    The application of manure-based commercial organic fertilizers (COFs) is becoming increasingly extensive because of the expanding market for organic food. The present study examined the effects of repeated applications of chicken or swine manure-based COFs on the fate of antibiotics and antibiotic resistance genes (ARGs) in soil by conducting a soil microcosm experiment. Application of COFs significantly increased antibiotics residues, as well as the relative abundance of ARGs and the integrase gene of class 1 integrons (intΙ1) in soil. Two months after each application, antibiotics and ARGs dissipated in amended soils, but they still remained at an elevated level, compared with the control. And, the accumulation of antibiotics was found due to repeated COF applications. However, the relative abundance of ARGs in most COF-amended soils did not differ significantly between the first application and the repeated application. The results imply that 2 months are not sufficient for ARGs to approach background levels, and that animal manure must be treated more effectively prior to using it in agriculture ecosystems.

  20. A review of the influence of treatment strategies on antibiotic resistant bacteria and antibiotic resistance genes.

    Science.gov (United States)

    Sharma, Virender K; Johnson, Natalie; Cizmas, Leslie; McDonald, Thomas J; Kim, Hyunook

    2016-05-01

    Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG) in the aquatic environment have become an emerging contaminant issue, which has implications for human and ecological health. This review begins with an introduction to the occurrence of ARB and ARG in different environmental systems such as natural environments and drinking water resources. For example, ARG or ARB with resistance to ciprofloxacin, sulfamethoxazole, trimethoprim, quinolone, vancomycin, or tetracycline (e.g., tet(A), tet(B), tet(C), tet(G), tet(O), tet(M), tet(W), sul I, and sul II) have been detected in the environment. The development of resistance may be intrinsic, may be acquired through spontaneous mutations (de novo), or may occur due to horizontal gene transfer from donor bacteria, phages, or free DNA to recipient bacteria. An overview is also provided of the current knowledge regarding inactivation of ARB and ARG, and the mechanism of the effects of different disinfection processes in water and wastewater (chlorination, UV irradiation, Fenton reaction, ozonation, and photocatalytic oxidation). The effects of constructed wetlands and nanotechnology on ARB and ARG are also summarized.

  1. Housefly Larva Vermicomposting Efficiently Attenuates Antibiotic Resistance Genes in Swine Manure, with Concomitant Bacterial Population Changes

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hang; Li, Hongyi; Gilbert, Jack A.; Li, Haibo; Wu, Longhua; Liu, Meng; Wang, Liling; Zhou, Qiansheng; Yuan, Junxiang; Zhang, Zhijian

    2015-11-01

    Manure from swine treated with antimicrobials as feed additives is a major source for the expansion of the antibiotic resistance gene (ARG) reservoir in the environment. Vermicomposting via housefly larvae (Musca domestica) can be efficiently used to treat manure and regenerate biofertilizer, but few studies have investigated its effect on ARG attenuation. Here, we tracked the abundances of 9 ARGs and the composition and structure of the bacterial communities in manure samples across 6 days of full-scale manure vermicomposting. On day 6, the abundances of genes encoding tetracycline resistance [tet(M), tet(O), tet(Q), and tet(W)] were reduced (P < 0.05), while those of genes encoding sulfonamide resistance (sul1 and sul2) were increased (P < 0.05) when normalized to 16S rRNA. The abundances of tetracycline resistance genes were correlated (P < 0.05) with the changing concentrations of tetracyclines in the manure. The overall diversity and richness of the bacteria significantly decreased during vermicomposting, accompanied by a 100 times increase in the relative abundance of Flavobacteriaceae spp. Variations in the abundances of ARGs were correlated with the changing microbial community structure and the relative abundances of the family Ruminococcaceae, class Bacilli, or phylum Proteobacteria. Vermicomposting, as a waste management practice, can reduce the overall abundance of ARGs. More research is warranted to assess the use of this waste management practice as a measure to attenuate the dissemination of antimicrobial residues and ARGs from livestock production before vermicompost can be safely used as biofertilizer in agroecosystems.

  2. Reclaimed water as a reservoir of antibiotic resistance genes: distribution system and irrigation implications

    Directory of Open Access Journals (Sweden)

    Nicole L Fahrenfeld

    2013-05-01

    Full Text Available Treated wastewater is increasingly being reused to achieve sustainable water management in arid regions. The objective of this study was to quantify the distribution of antibiotic resistance genes (ARGs in recycled water, particularly after it has passed through the distribution system, and to consider point-of-use implications for soil irrigation. Three separate reclaimed wastewater distribution systems in the western U.S. were examined. Quantitative polymerase chain reaction (qPCR was used to quantify ARGs corresponding to resistance to sulfonamides (sul1, sul2, macrolides (ermF, tetracycline (tet(A, tet(O, glycopeptides (vanA, and methicillin (mecA, in addition to genes present in waterborne pathogens Legionella pneumophila (Lmip, Escherichia coli (gadAB, and Pseudomonas aeruginosa (ecfx, gyrB. In a parallel lab study, the effect of irrigating an agricultural soil with secondary, chlorinated, or dechlorinated wastewater effluent was examined in batch microcosms. A broader range of ARGs were detected after the reclaimed water passed through the distribution systems, highlighting the importance of considering bacterial re-growth and the overall water quality at the point of use. Screening for pathogens with qPCR indicated presence of Lmip and gadAB genes, but not ecfx or gyrB. In the lab study, chlorination was observed to reduce 16S rRNA and sul2 gene copies in the wastewater effluent, while dechlorination had no apparent effect. ARGs levels did not change with time in soil slurries incubated after a single irrigation event with any of the effluents. However, when irrigated repeatedly with secondary wastewater effluent (not chlorinated or dechlorinated, elevated levels of sul1 and sul2 were observed. This study suggests that reclaimed water may be an important reservoir of ARGs, especially at the point of use, and that attention should be directed towards the fate of ARGs in irrigation water and the implications for human health.

  3. Behavior of antibiotics and antibiotic resistance genes in eco-agricultural system: A case study

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Weixiao; Li, Jianan; Wu, Ying; Xu, Like; Su, Chao; Qian, Yanyun [Department of Environmental Engineering, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Zhu, Yong-Guan [Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Chen, Hong, E-mail: chen_hong@zju.edu.cn [Department of Environmental Engineering, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

    2016-03-05

    Highlights: • TetQ had the highest relative abundance and tetG was the most persistent gene. • The anaerobic digestion has no effective removal of most ARGs. • The abundance of ARGs in soils and fishpond was higher than that of control system. • Positive correlations were observed between the total ARGs and TN, TP and TOC. - Abstract: This study aims to determine abundance and persistence of antibiotics and antibiotic resistance genes (ARGs) in eco-agricultural system (EAS), which starts from swine feces to anaerobic digestion products, then application of anaerobic digestion solid residue (ADSR) and anaerobic digestion liquid residue (ADLR) to the soil to grow ryegrass, one of swine feed. Oxytetracycline had the highest concentration in manure reaching up to 138.7 mg/kg. Most of antibiotics could be effectively eliminated by anaerobic digestion and removal rates ranged from 11% to 86%. ARGs abundance fluctuated within EAS. TetQ had the highest relative abundance and the relative abundance of tetG had the least variation within the system, which indicates that tetG is persistent in the agricultural environment and requires more attention. Compared to the relative abundance in manure, tetC and tetM increased in biogas residue while three ribosomal protection proteins genes (tetO, tetQ, tetW) decreased (p < 0.05), with other genes showing no significant change after anaerobic fermentation (p > 0.05). Most ARGs in downstream components (soils and fishpond) of EAS showed significantly higher relative abundance than the control agricultural system (p < 0.05), except for tetG and sulI.

  4. p16 gene silencing along with p53 single-nucleotide polymorphism and risk of esophageal cancer in Northeast India.

    Science.gov (United States)

    Das, Mandakini; Sharma, Santanu Kumar; Sekhon, Gaganpreet Singh; Mahanta, Jagadish; Phukan, Rup Kumar; Jalan, Bimal Kumar

    2017-05-01

    The high incidence of esophageal cancer in Northeast India and the unique ethnic background and dietary habits provide a great opportunity to study the molecular genetics behind esophageal squamous cell carcinoma in this part of the region. We hypothesized that in addition to currently known environmental risk factors for esophageal cancer, genetic and epigenetic factors are also involved in esophageal carcinogenesis in Northeast India. Therefore, in this study, we explored the possible association between the two important G1 cell cycle regulatory genes p16 and p53 and environmental risk factors and risk of esophageal carcinogenesis. A total of 100 newly diagnosed esophageal cancer cases along with equal number of age-, sex-, and ethnicity-matched controls were included in this study. Methylation-specific polymerase chain reaction was used to determine the p16 promoter methylation status. Single-nucleotide polymorphism at codon 72 of p53 gene was assessed by the polymerase chain reaction-restriction fragment length polymorphism method. Aberrant methylation of p16 gene was seen in 81% of esophageal cancer cases. Hypermethylation of p16 gene was not found in healthy controls. p53 Pro/Pro genotype was found to be a risk genotype in Northeast India compared with Arg/Pro and Arg/Arg. p53 variant/polymorphism was significantly associated with esophageal cancer risk in the study population under all three genetic models, namely, dominant model (Arg/Pro + Pro/Pro vs Arg/Arg odds ratio = 2.25, confidence interval = 1.19-4.26; p = 0.012), recessive model (Arg/Arg + Arg/Pro vs Pro/Pro odds ratio = 2.35, confidence interval = 1.24-4.44; p = 0.008), and homozygous model (Pro/Pro vs Arg/Arg odds ratio = 3.33, confidence interval = 1.54-7.20; p = 0.002). However, p53 variant/polymorphism was not statistically associated with esophageal cancer risk under the heterozygous model (Pro/Pro vs Arg/Pro). In the case-only analysis based on p16

  5. The tRNAarg gene and engA are essential genes on the 1.7-Mb pSymB megaplasmid of Sinorhizobium meliloti and were translocated together from the chromosome in an ancestral strain.

    Science.gov (United States)

    diCenzo, George; Milunovic, Branislava; Cheng, Jiujun; Finan, Turlough M

    2013-01-01

    Bacterial genomes with two (or more) chromosome-like replicons are known, and these appear to be particularly frequent in alphaproteobacteria. The genome of the N(2)-fixing alfalfa symbiont Sinorhizobium meliloti 1021 contains a 3.7-Mb chromosome and 1.4-Mb (pSymA) and 1.7-Mb (pSymB) megaplasmids. In this study, the tRNA(arg) and engA genes, located on the pSymB megaplasmid, are shown to be essential for growth. These genes could be deleted from pSymB when copies were previously integrated into the chromosome. However, in the closely related strain Sinorhizobium fredii NGR234, the tRNA(arg) and engA genes are located on the chromosome, in a 69-kb region designated the engA-tRNA(arg)-rmlC region. This region includes bacA, a gene that is important for intracellular survival during host-bacterium interactions for S. meliloti and the related alphaproteobacterium Brucella abortus. The engA-tRNA(arg)-rmlC region lies between the kdgK and dppF2 (NGR_c24410) genes on the S. fredii chromosome. Synteny analysis showed that kdgK and dppF2 orthologues are adjacent to each other on the chromosomes of 15 sequenced strains of S. meliloti and Sinorhizobium medicae, whereas the 69-kb engA-tRNA(arg)-rmlC region is present on the pSymB-equivalent megaplasmids. This and other evidence strongly suggests that the engA-tRNA(arg)-rmlC region translocated from the chromosome to the progenitor of pSymB in an ancestor common to S. meliloti and S. medicae. To our knowledge, this work represents one of the first experimental demonstrations that essential genes are present on a megaplasmid.

  6. 中国肥胖患者β_2 肾上腺素受体基因多态性的研究%Polymorphism in β_2 Adrenergic Receptor Gene in Chinese Population with Obesity

    Institute of Scientific and Technical Information of China (English)

    吴红梅; 白怀; 范平; 刘瑞; 刘宇; 刘秉文

    2009-01-01

    Objective To investigate the variation of β_2 adrenergic receptor (β_2AR) gene and its association with obesity in Chinese population. Methods The allele of β_2AR gene at Argl6Gly and Gln27Glu sites were analysed with polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) in 396 people with Han nationality in Chengdu, among whom 126 had obesity. Results The allele frequencies of Arg and Gly at Argl6Gly site were 0. 571 and 0. 429 for the obese people, and 0. 559 and 0. 441 for the non-obese people, respectively. The allele frequencies of Gin and Glu at Gln27Glu site were 0. 920 and 0. 080 for the obese people, and 0. 916 and 0. 084 for the non-obese people, respectively. No significant differences were found in the genotype frequencies of the two sites between non-obese and obese people. The non-obese females and obese males with genotype Arg/Arg at Argl6Gly site had elevated serum TC and LDL-C levels compared with those who carried Arg/ Gly or Gly/Gly (P0.05).在Arg16Gly位点,非肥胖组女性和肥胖组男性Arg/Arg基因型携带者血清 TC 和 LDLC 水平分别高于Arg/Gly和Gly/Gly基因型携带者(P0.05).结论 β_2AR基因Arg16Gly和Gln27Glu多态性与成都地区中国汉族人肥胖无关联,但Arg16Gly位点对特定性别非肥胖及肥胖人群血清TC、LDLC及部分载脂蛋白水平有一定影响.

  7. Inactivation of antibiotic resistance genes in municipal wastewater effluent by chlorination and sequential UV/chlorination disinfection.

    Science.gov (United States)

    Zhang, Yingying; Zhuang, Yao; Geng, Jinju; Ren, Hongqiang; Zhang, Yan; Ding, Lili; Xu, Ke

    2015-04-15

    This study investigated disinfection methods including chlorination, ultraviolet (UV) irradiation and sequential UV/chlorination treatment on the inactivation of antibiotic resistance genes (ARGs). ARGs including sul1, tetX, tetG, intI1, and 16S rRNA genes in municipal wastewater treatment plant (MWTP) effluent were examined. The results indicated a positive correlation between the removal of ARGs and chlorine dosage (p=0.007-0.014, n=6),as well as contact time (p=0.0001, n=10). Greater free chlorine (FC) dosage leads to higher removal for all the genes and the maximum removal (1.30-1.49 logs) could be achieved at FC dosage of 30 mg L(-1). The transformation kinetic data for ARGs removal (log C0/C) followed the second-order reaction kinetic model with FC dosage (R(2)=0.6829-0.9999) and contact time (R(2)=0.7353-8634), respectively. Higher ammonia nitrogen (NH3-N) concentration was found to lead to lower removal of ARGs at the same chlorine dosage. When the applied Cl2:NH3-N ratio was over 7.6:1, a significant reduction of ARGs (1.20-1.49 logs) was achieved. By using single UV irradiation, the log removal values of tetX and 16Ss rRNA genes were 0.58 and 0.60, respectively, while other genes were 0.36-0.40 at a fluence of 249.5 mJ cm(-2), which was observed to be less effective than chlorination. With sequential UV/chlorination treatment, 0.006 to 0.31 log synergy values of target genes were observed under different operation parameters.

  8. Fate of antibiotic resistance genes and its drivers during anaerobic co-digestion of food waste and sewage sludge based on microwave pretreatment.

    Science.gov (United States)

    Zhang, Junya; Chen, Meixue; Sui, Qianwen; Wang, Rui; Tong, Juan; Wei, Yuansong

    2016-10-01

    In this study, anaerobic digestion of mono-SS, MW-SS:FW and SS:MW-FW was investigated to understand the fate of ARGs and its drivers. Anaerobic digestion was effective for the reduction of metal resistance genes (MRGs), and could reduce the abundance of blaOXA-1, sulI and tetG, while sulII in co-digestion and blaTEM and ereA only in MW-SS. ARGs reduction could be partly attributed to the reduction of co-selective pressure from heavy metals reflected by MRGs. However, the abundance of mefA/E, ermB, ermF, tetM and tetX increased significantly. Anaerobic co-digestion, especially for MW-SS, could reduce total ARGs abundance compared with mono-SS, and evolution of bacterial community was the main driver for the fate of ARGs.

  9. MASS LOSS AND NITROGEN DYNAMICS DURING THE DECOMPOSITION OF A N-LABELED N2-FIXING EPOPHYTIC LICHEN, LOBARIA OREGANA (TUCK.) MULL. ARG.

    Science.gov (United States)

    We studied mass loss and nitrogen dynamics during fall and spring initiated decomposition of an N2-fixing epiphytic lichen, Lobaria oregana (Tuck.) Mull. Arg. using 15N. We developed a method of labeling lichens with 15N that involved spraying lichen material with a nutrient sol...

  10. Cell adhesion to fibrillin-1: identification of an Arg-Gly-Asp-dependent synergy region and a heparin-binding site that regulates focal adhesion formation

    DEFF Research Database (Denmark)

    Bax, Daniel V; Mahalingam, Yashithra; Cain, Stuart;

    2007-01-01

    We have defined the molecular basis of cell adhesion to fibrillin-1, the major structural component of extracellular microfibrils that are associated with elastic fibres. Using human dermal fibroblasts, and recombinant domain swap fragments containing the Arg-Gly-Asp motif, we have demonstrated a...

  11. Mutagenesis of residue betaArg-246 in the phosphate-binding subdomain of catalytic sites of Escherichia coli F1-ATPase.

    Science.gov (United States)

    Ahmad, Zulfiqar; Senior, Alan E

    2004-07-23

    Residues responsible for phosphate binding in F(1)F(0)-ATP synthase catalytic sites are of significant interest because phosphate binding is believed linked to proton gradient-driven subunit rotation. From x-ray structures, a phosphate-binding subdomain is evident in catalytic sites, with conserved betaArg-246 in a suitable position to bind phosphate. Mutations betaR246Q, betaR246K, and betaR246A in Escherichia coli were found to impair oxidative phosphorylation and to reduce ATPase activity of purified F(1) by 100-fold. In contrast to wild type, ATPase of mutants was not inhibited by MgADP-fluoroaluminate or MgADP-fluoroscandium, showing the Arg side chain is required for wild-type transition state formation. Whereas 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) inhibited wild-type ATPase essentially completely, ATPase in mutants was inhibited maximally by approximately 50%, although reaction still occurred at residue betaTyr-297, proximal to betaArg-246 in the phosphate-binding pocket. Inhibition characteristics supported the conclusion that NBD-Cl reacts in betaE (empty) catalytic sites, as shown previously by x-ray structure analysis. Phosphate protected against NBD-Cl inhibition in wild type but not in mutants. The results show that phosphate can bind in the betaE catalytic site of E. coli F(1) and that betaArg-246 is an important phosphate-binding residue.

  12. Primary structure of the precursor for the sea anemone neuropeptide Antho-RFamide (less than Glu-Gly-Arg-Phe-NH2)

    DEFF Research Database (Denmark)

    Darmer, D; Schmutzler, C; Diekhoff, D;

    1991-01-01

    Neuropeptides containing the carboxylterminal sequence Arg-Phe-NH2 are found throughout the animal kingdom and are important substances mediating neuronal communication. Here, we have cloned the cDNA coding for the precursor protein of the sea anemone neuropeptide (Antho-RFamide) less than Glu...

  13. High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype-Phenotype Correlation.

    Science.gov (United States)

    Rojnueangnit, Kitiwan; Xie, Jing; Gomes, Alicia; Sharp, Angela; Callens, Tom; Chen, Yunjia; Liu, Ying; Cochran, Meagan; Abbott, Mary-Alice; Atkin, Joan; Babovic-Vuksanovic, Dusica; Barnett, Christopher P; Crenshaw, Melissa; Bartholomew, Dennis W; Basel, Lina; Bellus, Gary; Ben-Shachar, Shay; Bialer, Martin G; Bick, David; Blumberg, Bruce; Cortes, Fanny; David, Karen L; Destree, Anne; Duat-Rodriguez, Anna; Earl, Dawn; Escobar, Luis; Eswara, Marthanda; Ezquieta, Begona; Frayling, Ian M; Frydman, Moshe; Gardner, Kathy; Gripp, Karen W; Hernández-Chico, Concepcion; Heyrman, Kurt; Ibrahim, Jennifer; Janssens, Sandra; Keena, Beth A; Llano-Rivas, Isabel; Leppig, Kathy; McDonald, Marie; Misra, Vinod K; Mulbury, Jennifer; Narayanan, Vinodh; Orenstein, Naama; Galvin-Parton, Patricia; Pedro, Helio; Pivnick, Eniko K; Powell, Cynthia M; Randolph, Linda; Raskin, Salmo; Rosell, Jordi; Rubin, Karol; Seashore, Margretta; Schaaf, Christian P; Scheuerle, Angela; Schultz, Meredith; Schorry, Elizabeth; Schnur, Rhonda; Siqveland, Elizabeth; Tkachuk, Amanda; Tonsgard, James; Upadhyaya, Meena; Verma, Ishwar C; Wallace, Stephanie; Williams, Charles; Zackai, Elaine; Zonana, Jonathan; Lazaro, Conxi; Claes, Kathleen; Korf, Bruce; Martin, Yolanda; Legius, Eric; Messiaen, Ludwine

    2015-11-01

    Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple café-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients.

  14. Site-directed mutagenesis of Arg58 and Asp86 of elongation factor Tu from Escherichia coli: effects on the GTPase reaction and aminoacyl-tRNA binding

    DEFF Research Database (Denmark)

    Knudsen, Charlotte Rohde; Clark, Brian F. C.

    1996-01-01

    Elongation factor Tu from Escherichia coli was mutated separately at positions Asp86 and Arg58, in order to shed light both on the GTPase mechanism of elongation factor Tu and on the binding of aminoacyl-tRNA. In addition, the binding of guanine nucleotides was investigated by determination...

  15. The effects of mutating Tyr9 and Arg15 on the structure, stability, conformational dynamics and mechanism of GSTA3-3

    CSIR Research Space (South Africa)

    Robertson, GJ

    2017-03-01

    Full Text Available GSTA1-1, its closest competitor in the Alpha class of GSTs. In order to examine the differences between Alpha class GSTs and to better elucidate the mechanism of GSTA3-3 the roles of Tyr9 and Arg15 were examined. Tyr9 is the major catalytic residue...

  16. Assessment of the Link between XRCC1 Arg399Gln Polymorphism and Breast Cancer: a Meta-Analysis in a Single Ethnic Group.

    Science.gov (United States)

    Chen, Xin-Ping; Wen, Hai-Feng; Zhang, Fan; Xu, Wei-Hua; Ma, Zhi-Chao; Fu, Sheng-Miao

    2017-04-01

    Although various individual studies have been conducted to determine the association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and breast cancer, the results remain inconclusive. To assess the influence of XRCC1 Arg399Gln polymorphism on the risk of breast cancer, a metaanalysis was performed in a single ethnic group. Eligible studies were identified via databases such as PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine, throughout February 2016. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strengths of the associations. Ten studies documenting a total of 4732 breast cancer cases and 5677 controls were included in this metaanalysis. The results indicated no significant association between XRCC1 Arg399Gln polymorphism and breast cancer risk in both total analysis and subgroup analysis stratified by geographical areas and source of controls. This meta-analysis provided evidence that XRCC1 Arg399Gln variant might not be risk alleles for breast cancer susceptibility in the Chinese population. Further studies conducted in other ethnic groups are required for definite conclusions.

  17. IL-10 and ARG-1 Concentrations in Bone Marrow and Peripheral Blood of Metastatic Neuroblastoma Patients Do Not Associate with Clinical Outcome

    Directory of Open Access Journals (Sweden)

    Fabio Morandi

    2015-01-01

    Full Text Available The expression of the immunosuppressive molecules IL-10 and arginase 1 (ARG-1, and of FOXP3 and CD163, as markers of regulatory T cells (Treg and macrophages, respectively, was evaluated in bone marrow (BM and peripheral blood (PB samples collected at diagnosis from patients with metastatic neuroblastoma (NB. IL-10 and ARG-1 plasma concentrations were measured and the association of each parameter with patients’ outcome was tested. The percentages of immunosuppressive Treg and type-1 regulatory (Tr1 cells were also determined. In both BM and PB samples, IL-10 mRNA expression was higher in metastatic NB patients than in controls. IL-10 plasma concentration was higher in patients with NB regardless of stage. Neither IL-10 expression nor IL-10 plasma concentration significantly associated with patient survival. In PB samples from metastatic NB patients, ARG-1 and CD163 expression was higher than in controls but their expression did not associate with survival. Moreover, ARG-1 plasma concentration was lower than in controls, and no association with patient outcome was found. Finally, in metastatic NB patients, the percentage of circulating Treg was higher than in controls, whereas that of Tr1 cells was lower. In conclusion, although IL-10 concentration and Treg percentage were increased, their contribution to the natural history of metastatic NB appears uncertain.

  18. Site-directed mutagenesis of Arg58 and Asp86 of elongation factor Tu from Escherichia coli: effects on the GTPase reaction and aminoacyl-tRNA binding

    DEFF Research Database (Denmark)

    Knudsen, Charlotte Rohde; Clark, Brian F. C.

    1996-01-01

    Elongation factor Tu from Escherichia coli was mutated separately at positions Asp86 and Arg58, in order to shed light both on the GTPase mechanism of elongation factor Tu and on the binding of aminoacyl-tRNA. In addition, the binding of guanine nucleotides was investigated by determination of th...

  19. Exploring the triad of behaviour, genes and neuronal networks: Heritability of instrumental conditioning and the Arc/Arg3.1 gene in hippocampal coding

    NARCIS (Netherlands)

    H.A.I. Malkki

    2013-01-01

    In this thesis, we set out to study the genetic background of neuronal function that enables adaptive behaviours that are essential for survival, such as understanding the relations between actions and outcomes and forming accurate representations of the environment. In the experimental protocols we

  20. Abundance of Antibiotic Resistance Genes in Bacteriophage following Soil Fertilization with Dairy Manure or Municipal Biosolids, and Evidence for Potential Transduction.

    Science.gov (United States)

    Ross, Joseph; Topp, Edward

    2015-11-01

    Animal manures and municipal biosolids recycled onto crop production land carry antibiotic-resistant bacteria that can influence the antibiotic resistome of agricultural soils, but little is known about the contribution of bacteriophage to the dissemination of antibiotic resistance genes (ARGs) in this context. In this work, we quantified a set of ARGs in the bacterial and bacteriophage fractions of agricultural soil by quantitative PCR. All tested ARGs were present in both the bacterial and phage fractions. We demonstrate that fertilization of soil with dairy manure or human biosolids increases ARG abundance in the bacterial fraction but not the bacteriophage fraction and further show that pretreatment of dairy manure can impact ARG abundance in the bacterial fraction. Finally, we show that purified bacteriophage can confer increased antibiotic resistance to soil bacteria when combined with selective pressure. The results indicate that soilborne bacteriophage represents a substantial reservoir of antibiotic resistance and that bacteriophage could play a significant role in the horizontal transfer of resistance genes in the context of an agricultural soil microbiome. Overall, our work reinforces the advisability of composting or digesting fecal material prior to field application and suggests that application of some antibiotics at subclinical concentrations can promote bacteriophage-mediated horizontal transfer of ARGs in agricultural soil microbiomes.

  1. A preliminary investigation on the occurrence and distribution of antibiotic resistance genes in the Beijiang River, South China

    Institute of Scientific and Technical Information of China (English)

    Zhenhao Ling; Ying Yang; Yuanli Huang; Shichun Zou; Tiangang Luan

    2013-01-01

    The occurrence of antibiotic resistance genes (ARGs) was investigated and quantified in 20 water samples collected in the Beijiang River,South China.Sulfonamide-and tetracycline-resistant bacteria were present in 17 and 14 of the collected 20 samples.For sulfonamide ARGs,sulⅠ and sulⅡ were frequently observed in the Beijiang River.The levels of sulⅠ were higher than sulⅡ (p < 0.05),with the mean values of (1.41 ± 1.12) × 10-2 and (1.58 ± 1.71) × 10-3 copies/16S rDNA,respectively.For tetracycline ARGs,tetG had the highest frequency,100%,followed by tetA (85%),tetO (85%),tetC (70%),tetX (60%),tetM (40%) and tetQ (20%),while tetE and tetS were not detected in all the samples from the Beijiang River.On the other hand,tetC had the highest concentration,ranging from 8.30 × 10-2 to 13.20 copies/16S rDNA.The poor correlation between ARGs and antibiotic concentrations revealed that the self-amplification and persistence of ARGs were the reasons that made ARGs exist in the water environment even though the antibiotic selecting pressure was absent.Because so few field measurements have been conducted for investigating the levels of ARGs in rivers in South China,this study provides an important insight on better understanding the occurrence and spread of ARGs in such an ecosystem.

  2. Origin of Hb A2' (Hb B2) [delta16(A13)Gly --> Arg (GGC --> CGC)].

    Science.gov (United States)

    Bennani, Mohcine; Mombo, Landry-Erik; Chaventre, André; Barakat, Amina; Ducrocq, Rolande; Nagel, Ronald L; Krishnamoorthy, Rajagopal

    2003-05-01

    On a field trip to the Dogon country (le Pays Dogon) in central Mali, we detected a high frequency of the Hb A2 abnormality, reaching higher numbers among blacksmiths (up to 12.4%) living in the same villages. In this report, by direct nucleotide sequencing and employing a polymerase chain reaction-restriction fragment length polymorphism approach, we show that the Hb A2 variant observed in the Dogon population is indeed Hb A2', also called Hb B2, and that in all of the cases the abnormal delta-globin gene is linked to a unique haplotype. The same haplotype was found linked to Hb A2' in the Herero population belonging to the South African Bantu-speaking Blacks from Namibia. Although the unique origin of this mutation in Africa is a possibility, a recurrent mutational event cannot be excluded because the linked beta cluster haplotype is one of the two major haplotypes found in all African populations. A study of populations from other regions of Africa is required to clarify this issue.

  3. Distributive characteristics of Ser49Gly and Gly389Arg genetic polymorphisms of β1-adrenoceptor in Chinese Han and Dai populations

    Institute of Scientific and Technical Information of China (English)

    Zhao-qian LIU; Hong-hao ZHOU; Jie LIU; Zhi-hua XIANG; Min-yu HU; Wei MO; Lian-sheng WANG; Dong-sheng OU-YANG; Nan HE; Dan WANG

    2006-01-01

    Aim: Genetic polymorphisms causing Ser49Gly and Gly389Arg mutants of β1-adrenoceptor may result in significant changes in the function of this receptor.The aim of the present study was to investigate the frequencies of the Ser49Gly and Gly389Arg mutant alleles in healthy Chinese populations and to investigate the differences between 2 Chinese ethnic groups (Han and Dai populations) with respect to the frequencies of these alleles. Methods: A total of 225 Han Chinese and 175 Dai Chinese unrelated healthy volunteers were recruited for this study.Genomic DNA was extracted from peripheral blood leukocytes by using a standard manual chloroform-phenol extraction. Fragments spanning the 2 polymorphisms were amplified by using polymerase chain reaction with template genomic DNA and relevant primers. The DNA products including the polymorphic loci were subjected to restriction endonuclease digestion with Eco0l09I and BcgI.Digested fragments were detected with an ultraviolet detector after electrophoresis (100 V for approximately 1.5 h). Results: The frequencies of the Gly49 and Arg389 alleles were, respectively, 16.2% and 76.4% in the Han population and 14.6%and 75.7% in the Dai population. Conclusion: The polymorphisms causing the Ser49Gly and Gly389Arg mutations of the β1-adrenoceptor existed in both healthy Han and Dai Chinese populations. The frequencies of the Ser49Gly and Gly389Arg mutant alleles were not significantly different in the Han and Dai populations.However, the frequency of the Gly389 variant seems to be significantly lower in these 2 populations than in an African-American population.

  4. 妊娠湖羊补充 L-Arg 和 Se 对新生羔羊血清参数的影响%Effects of L-Arg and Selenium Supplementation to Pregnant Hu Sheep on Serum Parameters of Newborn Lambs

    Institute of Scientific and Technical Information of China (English)

    王连群; 侯芳; 郭同军; 李静溪; 马春晖

    2015-01-01

    为外源性精氨酸(Arg)和硒(Se)在养羊生产上的应用提供参考,选取体重相近、同期发情处理的已孕湖羊20只,随机平均分为4组(饲喂相同的基础日粮),即 Se 组:于妊娠期50 d 至分娩在基础日粮中额外添加 Se 0.2 mg/kg;Arg 组:于妊娠期130 d 至分娩每天静脉注射 L-Arg 70 mg/kg 体重;AS 组:Se 组和 Arg 组联用;对照组(CK):饲喂基础日粮。各组羊只分娩后立即采集新生羔羊的血液进行测定分析,以探明外源性 Arg 和 Se 通过母体对新生羔羊血清参数的影响。结果表明:1)与对照组比较,AS 组血清超氧化物歧化酶活力显著增加(P <0.05),Se 组和 AS 组血清谷胱甘肽过氧化物酶活力极显著增加(P <0.01)。2)AS组血清精氨酸含量显著高于 Se 组(P <0.05),极显著高于对照组(P <0.01);Arg 组血清精氨酸含量显著高于对照组(P <0.05)。Arg 组、AS 组的血清鸟氨酸含量均显著高于 Se 组和对照组(P <0.05)。3)AS组、Se 组的血清 Se 含量极显著高于 Arg 组和对照组(P <0.01)。妊娠湖羊日粮添加 Se 或与静脉注射L-Arg 联用能够提高新生羔羊机体的抗氧化性,单独进行静脉注射 L-Arg 或与日粮添加 Se 联用能显著增加新生羔羊血清中的 Arg 和鸟氨酸含量,有利于新生羔羊的生长发育。%To provide a reference for application of exogenous Arg and Se in sheep husbandry,20 pregnant Hu Sheep ewes with similar weight and estrus synchronization were selected and allotted randomly into four groups (five in each group,fed the same basal diet),namely:Se group (supplemented with 0.2 mg/kg of Se added to the basal diet every day during the 50 days of pregnancy to childbirth),Arg group (intravenous injection of 70 mg/kg BW d of L-Arg every day during the 130 days of pregnancy to childbirth),the AS group (supplemented with 0.2 mg/kg of Se

  5. Reduction of antibiotic resistance genes in municipal wastewater effluent by advanced oxidation processes

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingying; Zhuang, Yao; Geng, Jinju, E-mail: jjgeng@nju.edu.cn; Ren, Hongqiang; Xu, Ke; Ding, Lili

    2016-04-15

    This study investigated the reduction of antibiotic resistance genes (ARGs), intI1 and 16S rRNA genes, by advanced oxidation processes (AOPs), namely Fenton oxidation (Fe{sup 2+}/H{sub 2}O{sub 2}) and UV/H{sub 2}O{sub 2} process. The ARGs include sul1, tetX, and tetG from municipal wastewater effluent. The results indicated that the Fenton oxidation and UV/H{sub 2}O{sub 2} process could reduce selected ARGs effectively. Oxidation by the Fenton process was slightly better than that of the UV/H{sub 2}O{sub 2} method. Particularly, for the Fenton oxidation, under the optimal condition wherein Fe{sup 2+}/H{sub 2}O{sub 2} had a molar ratio of 0.1 and a H{sub 2}O{sub 2} concentration of 0.01 mol L{sup −1} with a pH of 3.0 and reaction time of 2 h, 2.58–3.79 logs of target genes were removed. Under the initial effluent pH condition (pH = 7.0), the removal was 2.26–3.35 logs. For the UV/H{sub 2}O{sub 2} process, when the pH was 3.5 with a H{sub 2}O{sub 2} concentration of 0.01 mol L{sup −1} accompanied by 30 min of UV irradiation, all ARGs could achieve a reduction of 2.8–3.5 logs, and 1.55–2.32 logs at a pH of 7.0. The Fenton oxidation and UV/H{sub 2}O{sub 2} process followed the first-order reaction kinetic model. The removal of target genes was affected by many parameters, including initial Fe{sup 2+}/H{sub 2}O{sub 2} molar ratios, H{sub 2}O{sub 2} concentration, solution pH, and reaction time. Among these factors, reagent concentrations and pH values are the most important factors during AOPs. - Highlights: • AOPs including Fenton oxidation and UV/H{sub 2}O{sub 2} process could reduce ARGs effectively. • Fenton oxidation is slightly more effective than UV/H{sub 2}O{sub 2} process in ARG reduction. • Removal of ARGs by AOPs follows the first-order reaction kinetic model. • Selected ARGs and 16S rRNA genes exhibit similar change trends during AOPs.

  6. Substitution of the Lys linker with the β-Ala linker dramatically decreased the renal uptake of 99mTc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone peptides.

    Science.gov (United States)

    Flook, Adam M; Yang, Jianquan; Miao, Yubin

    2014-11-13

    The purpose of this study was to examine whether the substitution of the Lys linker with the β-Ala could reduce the renal uptake of (99m)Tc-labeled Arg-X-Asp-conjugated and X-Ala-Asp-conjugated α-melanocyte stimulating hormone (α-MSH) peptides. RSD-β-Ala-(Arg(11))CCMSH (1) {c[Arg-Ser-Asp-dTyr-Asp]-β-Ala-Cys-Cys-Glu-His-dPhe-Arg-Trp-Cys-Arg-Pro-Val-NH2}, RTD-β-Ala-(Arg(11))CCMSH (2), RVD-β-Ala-(Arg(11))CCMSH (3), RAD-β-Ala-(Arg(11))CCMSH (4), NAD-β-Ala-(Arg(11))CCMSH (5), and EAD-β-Ala-(Arg(11))CCMSH (6) peptides were synthesized and evaluated for their melanocortin 1 (MC1) receptor binding affinities in B16/F1 melanoma cells. The biodistribution of their (99m)Tc-conjugates were determined in B16/F1 melanoma-bearing C57 mice. The substitution of the Lys linker with β-Ala linker dramatically reduced the renal uptake of all six (99m)Tc-peptides. (99m)Tc-4 exhibited the highest melanoma uptake (15.66 ± 6.19% ID/g) and the lowest kidney uptake (20.18 ± 3.86% ID/g) among these (99m)Tc-peptides at 2 h postinjection. The B16/F1 melanoma lesions could be clearly visualized by single photon emission computed tomography (SPECT)/CT using (99m)Tc-4 as an imaging probe.

  7. Report on a 2009 mini-demonstration of the ARG-US Radio Frequency Identification (RFID) system in transportation.

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Chen, K.; Jusko, M.; Craig, B.; Liu, Y.; Decision and Information Sciences

    2009-11-23

    The Packaging Certification Program (PCP) of the U.S. Department of Energy (DOE) Environmental Management (EM), Office of Packaging and Transportation (EM-14), has developed a radio frequency identification (RFID) tracking and monitoring system for the management of nuclear materials during storage and transportation. The system, developed by the PCP team at Argonne National Laboratory, consists of hardware (Mk-series sensor tags, fixed and handheld readers, form factor for multiple drum types, seal integrity sensors, and enhanced battery management), software (application programming interface, ARG-US software for local and remote/web applications, secure server and database management), and cellular/satellite communication interfaces for vehicle tracking and item monitoring during transport. The ability of the above system to provide accurate, real-time tracking and monitoring of the status of multiple, certified containers of nuclear materials has been successfully demonstrated in a week-long, 1,700-mile DEMO performed in April 2008. While the feedback from the approximately fifty (50) stakeholders who participated in and/or observed the DEMO progression were very positive and encouraging, two major areas of further improvements - system integration and web application enhancement - were identified in the post-DEMO evaluation. The principal purpose of the MiniDemo described in this report was to verify these two specific improvements. The MiniDemo was conducted on August 28, 2009. In terms of system integration, a hybrid communication interface - combining the RFID item-monitoring features and a commercial vehicle tracking system by Qualcomm - was developed and implemented. In the MiniDemo, the new integrated system worked well in reporting tag status and vehicle location accurately and promptly. There was no incompatibility of components. The robust commercial communication gear, as expected, helped improve system reliability. The MiniDemo confirmed that system

  8. Report on a 2009 mini-demonstration of the ARG-US Radio Frequency Identification (RFID) system in transportation.

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, H.; Chen, K.; Jusko, M.; Craig, B.; Liu, Y.; Decision and Information Sciences

    2009-11-23

    The Packaging Certification Program (PCP) of the U.S. Department of Energy (DOE) Environmental Management (EM), Office of Packaging and Transportation (EM-14), has developed a radio frequency identification (RFID) tracking and monitoring system for the management of nuclear materials during storage and transportation. The system, developed by the PCP team at Argonne National Laboratory, consists of hardware (Mk-series sensor tags, fixed and handheld readers, form factor for multiple drum types, seal integrity sensors, and enhanced battery management), software (application programming interface, ARG-US software for local and remote/web applications, secure server and database management), and cellular/satellite communication interfaces for vehicle tracking and item monitoring during transport. The ability of the above system to provide accurate, real-time tracking and monitoring of the status of multiple, certified containers of nuclear materials has been successfully demonstrated in a week-long, 1,700-mile DEMO performed in April 2008. While the feedback from the approximately fifty (50) stakeholders who participated in and/or observed the DEMO progression were very positive and encouraging, two major areas of further improvements - system integration and web application enhancement - were identified in the post-DEMO evaluation. The principal purpose of the MiniDemo described in this report was to verify these two specific improvements. The MiniDemo was conducted on August 28, 2009. In terms of system integration, a hybrid communication interface - combining the RFID item-monitoring features and a commercial vehicle tracking system by Qualcomm - was developed and implemented. In the MiniDemo, the new integrated system worked well in reporting tag status and vehicle location accurately and promptly. There was no incompatibility of components. The robust commercial communication gear, as expected, helped improve system reliability. The MiniDemo confirmed that system

  9. β3-Adrenergic receptor gene polymorphism and type 2 diabetes in a Caucasian population

    NARCIS (Netherlands)

    Oeveren van-Dybicz, A.M.; Vonkeman, H.E.; Bon, M.A.M.; Bergh, van den F.A.J.T.M.; Vermes, I.

    2008-01-01

    Aim: The β3-adrenergic receptor (β3-AR) is suspected to play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. A mutation in the β3-AR gene (Trp64Arg) has been associated with the capacity of weight gain and with early onset of noninsulin dependent diabetes me

  10. β3-Adrenergic receptor gene polymorphism and type 2 diabetes in a Caucasian population

    NARCIS (Netherlands)

    Oeveren van-Dybicz, A.M.; Vonkeman, Harald Erwin; Bon, M.A.M.; van den Bergh, F.A.J.T.M.; Vermes, I.

    2008-01-01

    Aim: The β3-adrenergic receptor (β3-AR) is suspected to play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. A mutation in the β3-AR gene (Trp64Arg) has been associated with the capacity of weight gain and with early onset of noninsulin dependent diabetes

  11. Fate of antimicrobials and antimicrobial resistance genes in simulated swine manure storage

    Science.gov (United States)

    The behavior of three antibiotics (bacitracin, chlortetracycline, and tylosin) and two classes of antibiotic resistance genes (ARGs), tet and erm, were monitored in swine manure slurry under anaerobic conditions. First-order decay rates were determined for each antibiotic with half-lives ranging fr...

  12. TP53 gene polymorphisms at codons 11, 72, and 248 and association with endometriosis in a Brazilian population.

    Science.gov (United States)

    Camargo-Kosugi, C M; D'Amora, P; Kleine, J P F O; Carvalho, C V; Sato, H; Schor, E; Silva, I D C G

    2014-08-26

    We evaluated the association between TP53 gene polymorphisms and endometriosis in Brazilian women. Genomic DNA was extracted from swabs of buccal cells collected from hospital patients. TP53 gene polymorphisms were investigated at three codons: TP53 11 Glu/Gln or Lys (GAG->CAG or AAG), TP53 72 Arg/Pro (CCG->CCC), and TP53 248 Arg/Thr (CGG->TCG) using the polymerase chain reaction-restriction fragment length polymorphism method. TP53 11 presented the following genotypic distribution: the control group was 98.28% homozygous wild-type (Glu) and 1.72% homozygous variant (Gln/Lys), and the heterozygous genotype was not identified. The genotypic distribution in the endometriosis group was 96% homozygous wild-type (Glu) and 4% heterozygous (Glu-Gln/Lys); the homozygous variant genotype was not identified (P = 0.02). TP53 72 showed the following genotypic distribution: the control group was 29.75% homozygous wild-type (Arg), 47.11% heterozygous (Arg-Pro), and 23.14% homozygous variant (Pro). The genotypic distribution in the endometriosis group was 16.15% homozygous wild-type (Arg), 51.54% heterozygous (Arg-Pro), and 32.31% homozygous variant (Pro) (odds ratio = 2.26; 95% confidence interval = 1.19-4.03; P = 0.02). Only one patient had the homozygous TP53 248 genotype (Arg-Trp/Gln); all other patients were homozygous wild-type in both the control and endometriosis groups (P = 0.51; NS). We found that TP53 72 polymorphism may be associated with susceptibility to endometriosis; the presence of at least 1 polymorphic allele increased the chance of disease development by 2.26-fold. Hence, this genetic variant is a potential candidate marker for endometriosis.

  13. Identification of minor secondary metabolites from the latex of Croton lechleri (Muell-Arg) and evaluation of their antioxidant activity.

    Science.gov (United States)

    De Marino, Simona; Gala, Fulvio; Zollo, Franco; Vitalini, Sara; Fico, Gelsomina; Visioli, Francesco; Iorizzi, Maria

    2008-01-01

    Dragon's blood (Sangre de drago), a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae), is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-beta-O-4'- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods ((1)H-, (13)C- NMR and 2D-NMR experiments), ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex) exhibited the highest antioxidant activity.

  14. Assessment of haemolytic, cytotoxic and free radical scavenging activities of an underutilized fruit, Baccaurea ramiflora Lour. (Roxb.) Muell. Arg.

    Science.gov (United States)

    Saha, Manas Ranjan; Dey, Priyankar; Chaudhuri, Tapas Kumar; Goyal, Arvind Kr; Sarker, Dilip De; Sen, Arnab

    2016-02-01

    Baccaurea ramiflora Lour. (Roxb.) Muell. Arg. is an underutilized juicy fruit bearing plant found in sub-Himalayan area, South China, Indo-Burma region, etc. The fruit is considered to be nutritive, and in this study, we evaluated its antioxidant, haemolytic and cytotoxic properties. The juice was examined for the quenching activity of hydroxyl radical, nitric oxide, singlet oxygen, peroxynitrite, total antioxidant activity (TAA), erythrocyte membrane stabilizing activity (EMSA) along with quantification of phenolic and flavonoid contents and also tested for its potential activity as iron chelator, inhibitor of lipid peroxidation and total reducing power. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were also performed to correlate antioxidant capacities with the phenolic and flavonoid content. Haemolytic activity on murine erythrocyte and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cytotoxic test was performed on murine splenocytes, thymocytes, hepatocytes and peritoneal exudates macrophage to examine the cytotoxic effect of its juice. The result exhibited its potent free radical scavenging activity. In case of TAA, DPPH (2, 2-diphenyl-1-picrylhydrazyl), EMSA and lipid peroxidation, the fruit juice was found to have significant (P cytotoxic test confirms that the juice does not contain any cytotoxic effect and the fruit is safe for consumption. Fourier transform infrared (FTIR) spectra analysis exhibited high possibility of presence of flavonoid compounds in the juice.

  15. Growth of endothelial cells on different concentrations of Gly-Arg-Gly-Asp photochemically grafted in polyethylene glycol modified polyurethane.

    Science.gov (United States)

    Lin, Y S; Wang, S S; Chung, T W; Wang, Y H; Chiou, S H; Hsu, J J; Chou, N K; Hsieh, K H; Chu, S H

    2001-08-01

    To improve endothelial cell adhesion and growth on the surface of polyethylene glycol modified polyurethane (PU-PEG), cell adhesive peptide Gly-Arg-Gly-Asp (GRGD) was photochemically grafted to the surface. The surface grafted GRGD-N-Succinimidyl-6-[4'-azido-2'-nitrophenylamino]hexanoate (SANPAH) on a PU-PEG surface was performed by adsorption and subsequent ultraviolet irradiation. Fourier transform infrared spectra (FTIR) and electron spectroscopy for chemical analysis (ESCA) confirmed the GRGD grafted to form a PU-PEG-GRGD surface. The composition fraction of nitrogen calculated from ESCA analysis for the PU-PEG-GRGD surface was well correlated with the concentration of GRGD to be immobilized. Human umbilical vein endothelial cells (ECs) were well adhered and growing on the PU-PEG-GRGD surface. Moreover, the viability of ECs growing on PU-PEG-GRGD surfaces, analyzed by MTT test, was also well correlated with the GRGD concentrations immobilized on the surface. With photochemical techniques, we could manipulate different contents of GRGD to form multiple regions of PU-PEG-GRGD surface that could enhance the growth of ECs on the surface, and the enhancement efficiency was well correlated with GRGD contents.

  16. Identification of Minor Secondary Metabolites from the Latex of Croton lechleri (Muell-Arg and Evaluation of Their Antioxidant Activity

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    Maria Iorizzi

    2008-06-01

    Full Text Available Dragon’s blood (Sangre de drago, a viscous red sap derived from Croton lechleri Muell-Arg (Euphorbiaceae, is extensively used by indigenous cultures of the Amazonian basin for its wound healing properties. The aim of this study was to identify the minor secondary metabolites and test the antioxidant activity of this sustance. A bioguided fractionation of the n-hexane, chloroform, n-butanol, and aqueous extracts led to the isolation of 15 compounds: three megastigmanes, four flavan-3-ols, three phenylpropanoids, three lignans, a clerodane, and the alkaloid taspine. In addition to these known molecules, six compounds were isolated and identified for the first time in the latex: blumenol B, blumenol C, 4,5-dihydroblumenol A, erythro-guaiacyl-glyceryl-β-O-4’- dihydroconiferyl ether, 2-[4-(3-hydroxypropyl-2-methoxyphenoxy]-propane-1,3-diol and floribundic acid glucoside. Combinations of spectroscopic methods (1H-, 13C- NMR and 2D-NMR experiments, ESI-MS, and literature comparisons were used for compound identification. In vitro antioxidant activities were assessed by DPPH, total antioxidant capacity and lipid peroxidation assays. Flavan-3-ols derivatives (as major phenolic compounds in the latex exhibited the highest antioxidant activity.

  17. Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity

    DEFF Research Database (Denmark)

    Andersen, Kirstine Lynge; Echwald, Søren Morgenthaler; Larsen, Lesli Hingstrup

    2005-01-01

    Obesity is a prominent feature of the Bardet-Biedl syndrome (BBS), one subset of which, BBS6, is due to mutations in the chaperonin-like gene termed the McKusick-Kaufman syndrome (MKKS) gene. We tested whether variation in MKKS contributes to common and probably polygenic forms of obesity...... by performing mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. Five variants were identified, including two synonymous mutations (Pro(39)Pro and Ile(178)Ile) and three nonsynonymous variants (Ala(242)Ser, Arg(517)Cys, and Gly(532)Val). Furthermore, the rare Ala(242)Ser...... was identified in two families and showed partial cosegregation with obesity. The Pro(39)Pro, Ile(178)Ile, and Arg(517)Cys variants are in complete linkage disequilibrium and defined a prevalent haplotype. In a case-control study, the Arg(517)Cys polymorphism allele prevalence was 11.4% [95% confidence interval...

  18. Polymorphisms of the DNA repair genes XRCC1 and XRCC3 in a Brazilian population

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    Duarte Márcia Cristina

    2005-01-01

    Full Text Available In several DNA repair genes, polymorphisms may result in reduced repair capacity, which has been implicated as a risk factor for various types of cancer. The frequency of the polymorphic alleles varies among populations, suggesting an ethnic distribution of genotypes. We genotyped 300 healthy Southeastern Brazilian individuals (262 of European ancestry and 38 of African ancestry for polymorphisms of codons 194 and 399 of the XRCC1 base excision repair pathway gene and of codon 241 of the XRCC3 homologous recombination repair pathway gene. The allele frequencies were 0.07 for the Arg194Trp and 0.33 for the Arg399Gln codons of the XRCC1 gene and 0.35 for the Thr241Met codon of the XRCC3 gene. The genotypic frequencies were within Hardy-Weinberg equilibrium. These frequencies showed ethnic variability when compared with those obtained for different populations from several countries.

  19. Excretion of antibiotic resistance genes by dairy calves fed milk replacers with varying doses of antibiotics

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    Callie H. Thames

    2012-04-01

    Full Text Available Elevated levels of antibiotic resistance genes (ARGs in soil and water have been linked to livestock farms and in some cases feed antibiotics may select for antibiotic resistant gut microbiota. The purpose of this study was to examine the establishment of ARGs in the feces of calves receiving milk replacer containing no antibiotics versus subtherapeutic or therapeutic doses of tetracycline and neomycin. The effect of antibiotics on calf health was also of interest. Twenty-eight male and female dairy calves were assigned to one of the three antibiotic treatment groups at birth and fecal samples were collected at weeks 6, 7 (prior to weaning, and 12 (5 weeks after weaning. ARGs corresponding to the tetracycline (tetC, tetG, tetO, tetW, and tetX, macrolide (ermB, ermF, and sulfonamide (sul1, sul2 classes of antibiotics along with the class I integron gene, intI1, were monitored by quantitative polymerase chain reaction as potential indicators of direct selection, co-selection, or horizontal gene transfer of ARGs. Surprisingly, there was no significant effect of antibiotic treatment on the absolute abundance (gene copies/ g wet manure of any of the ARGs except ermF, which was lower in the antibiotic-treated calf manure, presumably because a significant portion of host bacterial cells carrying ermF were not resistant to tetracycline or neomycin. However, relative abundance (gene copies normalized to 16S rRNA genes of tetO was higher in calves fed the highest dose of antibiotic than in the other treatments. All genes, except tetC and intI1, were detectable in feces from 6 weeks onwards, and tetW and tetG significantly increased (P<0.10, even in control calves. Overall, the results provide new insight into the colonization of calf gut flora with ARGs in the early weeks. Although feed antibiotics exerted little effect on the ARGs monitored in this study, the fact that they also provided no health benefit suggests that the greater than conventional

  20. Characterization of Antibiotics and Antibiotic Resistance Genes on an Ecological Farm System

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    Songhe Zhang

    2015-01-01

    Full Text Available There is a growing concern worldwide about the prevalence of antibiotics and antibiotic resistance genes (ARGs on the farm. In this study, we investigated the distribution of seven antibiotics and ten ARGs in fresh and dried pig feces, in biogas slurry, and in grape-planting soil from an ecological farm. Antibiotics including sulfamethazine, norfloxacin, ofloxacin, tetracycline, oxytetracycline, and chlortetracycline were detected in these samples (except for sulfamethoxazole in dried feces. In general, antibiotics levels in samples were in the sequence: biogas slurry > fresh feces > soil or dried feces. Results of ecological risk assessments revealed that among the seven antibiotics chlortetracycline showed the highest ecological risk. Among the ten ARGs, sulI and tetO were the most prevalent on this ecological farm. There were positive correlations between certain ARGs and the corresponding antibiotics on this ecological farm. Therefore, continuous monitoring of antibiotics and their corresponding ARGs should be conducted in the agroecosystem near the concentrated animal farming operation systems.

  1. Removal of antibiotics and antibiotic resistance genes in rural wastewater by an integrated constructed wetland.

    Science.gov (United States)

    Chen, Jun; Liu, You-Sheng; Su, Hao-Chang; Ying, Guang-Guo; Liu, Feng; Liu, Shuang-Shuang; He, Liang-Ying; Chen, Zhi-Feng; Yang, Yong-Qiang; Chen, Fan-Rong

    2015-02-01

    Integrated constructed wetlands (ICWs) are regarded as one of the most important removal technology for pollutants in rural domestic wastewaters. This study investigated the efficiency of an ICW consisting of a regulating pool, four surface and subsurface flow-constructed wetlands, and a stabilization unit for removing antibiotics and antibiotic resistance genes (ARGs) from rural domestic wastewaters. The results showed that antibiotics leucomycin, ofloxacin, lincomycin, and sulfamethazine, and ARGs sul1, sul2, tetM, and tetO were the predominant antibiotics and ARGs in the influent, respectively. The ICW system could significantly reduce most of the detected antibiotics and ARGs with their aqueous removal rates of 78 to 100 % and >99 %, respectively. Based on the measured concentrations, the total pollution loadings of antibiotics were 3,479 μg/day in the influent and 199 μg/day in the final effluent. Therefore, constructed wetlands could be a promising technology for rural wastewater in removing contaminants such as antibiotics and ARGs.

  2. Epistatic interaction between beta2-adrenergic receptor and neuropeptide Y genes influences LDL-cholesterol in hypertension.

    Science.gov (United States)

    Tomaszewski, Maciej; Charchar, Fadi J; Lacka, Beata; Pesonen, Ullamari; Wang, William Y S; Zukowska-Szczechowska, Ewa; Grzeszczak, Wladyslaw; Dominiczak, Anna F

    2004-11-01

    Beta2-adrenergic receptor gene and neuropeptide Y gene may potentially influence lipid metabolism and overall energy balance. Therefore, we examined associations of these genes with lipid fractions and obesity-related phenotypes in hypertensive subjects. A total of 638 white individuals from 212 Polish families with clustering of essential hypertension were phenotyped for cardiovascular risk determinants. Each subject was genotyped for functional polymorphisms of beta2-adrenergic receptor gene (Arg16Gly and Gln27Glu) and neuropeptide Y (Leu7Pro). Of 3 common haplotypes of beta2-adrenergic receptor gene, Arg16Gln27 was overtransmitted to offspring with elevated levels of total cholesterol (Z=2.2; P=0.026) and LDL-cholesterol (Z=3.2; P=0.002). Individually, Leu7Pro was not associated with any of the metabolic phenotypes in family-based tests or case-control analyses. However, in the presence of Arg allele of Arg16Gly and Gln allele of Gln27Glu, homozygosity for Leu variant of the Leu7Pro polymorphism was associated with 2.1-increased odds ratio (confidence interval, 1.10 to 3.81; P=0.024) of elevated LDL in hypertensive subjects, independent of age, gender, body mass index, adjusted blood pressures, antihypertensive therapy, and use of nonselective beta-blockers and diuretics. Consistently, there was a significant multilocus association among variants of Arg16Gly, Gln27Glu, and Leu7Pro in hypertensive probands with elevated LDL (cases; P=0.028) but not in hypertensive subjects with normal LDL (controls). This study revealed an association of LDL-cholesterol with beta2-adrenergic receptor gene haplotype and provided evidence for epistatic interaction between beta2-adrenergic receptor gene and neuropeptide Y gene in determination of LDL-cholesterol in patients with essential hypertension.

  3. Sulfonamide and tetracycline resistance genes in total- and culturable-bacterial assemblages in South African aquatic environments

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    Satoru eSuzuki

    2015-08-01

    Full Text Available Antibiotic resistant bacteria (ARB are ubiquitous in the natural environment. The introduction of effluent derived antibiotic resistance genes (ARGs into aquatic environments is of concern in the spreading of genetic risk. This study showed the prevalence of sulfonamide and tetracycline resistance genes, sul1, sul2, sul3 and tet(M, in the total bacterial assemblage and colony forming bacterial assemblage in river and estuarine water and sewage treatment plants (STP in South Africa. There was no correlation between antibiotic concentrations and ARGs, suggesting the targeted ARGs are spread in a wide area without connection to selection pressure. Among sul genes, sul1 and sul2 were major genes in the total (over 10-2 copies/16S and colony forming bacteria assemblages (approx 10-1 copies/16S. In urban waters, the sul3 gene was mostly not detectable in total and culturable assemblages, suggesting sul3 is not abundant. tet(M was found in natural assemblages with 10-3 copies/16S level in STP, but was not detected in colony forming bacteria, suggesting the non-culturable (yet-to-be cultured bacterial community in urban surface waters and STP effluent possess the tet(M gene. Sulfamethoxazole resistant (SMXr and oxytetracycline resistant (OTCr bacterial communities in urban waters possessed not only sul1 and sul2 but also sul3 and tet(M genes. These genes are widely distributed in SMXr and OTCr bacteria. In conclusion, urban river and estuarine water and STP effluent in the Durban area were highly contaminated with ARGs, and the yet-to-be cultured bacterial community may act as a non-visible ARG reservoir in certain situations.

  4. Dynamics of antibiotic resistance genes in microbial fuel cell-coupled constructed wetlands treating antibiotic-polluted water.

    Science.gov (United States)

    Zhang, Shuai; Song, Hai-Liang; Yang, Xiao-Li; Huang, Shan; Dai, Zhe-Qin; Li, Hua; Zhang, Yu-Yue

    2017-07-01

    Microbial fuel cell-coupled constructed wetlands (CW-MFCs) use electrochemical, biological, and ecological functions to treat wastewater. However, few studies have investigated the risks of antibiotic resistance genes (ARGs) when using such systems to remove antibiotics. Therefore, three CW-MFCs were designed to assess the dynamics of ARGs in filler biofilm and effluent over 5000 h of operation. The experimental results indicated that relatively high steady voltages of 605.8 mV, 613.7 mV, and 541.4 mV were obtained at total influent antibiotic concentrations of 400, 1,000, and 1600 μg L(-1), respectively. The 16S rRNA gene level in the cathode layer was higher than those in the anode and two middle layers, but the opposite trend was observed for the sul and tet genes. The relative abundance of the three tested sul genes were in the order sulI > sulII > sulIII, and those of the five tet genes were in the order tetA > tetC > tetW > tetO > tetQ. The levels of sul and tet genes in the media biofilm showed an increase over the treatment period. The effluent water had relatively low abundances of sul and tet genes compared with the filler biofilm. No increases were observed for most ARGs over the treatment period, and no significant correlations were observed between the ARGs and 16S rRNA gene copy numbers, except for sulI and tetW in the effluent. However, significant correlations were observed among most of the ARG copy numbers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. High frequencies of antibiotic resistance genes in infants’ meconium and early fecal samples

    DEFF Research Database (Denmark)

    Gosalbes, M. J.; Vallès, Y.; Jiménez-Hernández, N.

    2016-01-01

    The gastrointestinal tract (GIT) microbiota has been identified as an important reservoir of antibiotic resistance genes (ARGs) that can be horizontally transferred to pathogenic species. Maternal GIT microbes can be transmitted to the offspring, and recent work indicates that such transfer starts...... before birth. We have used culture-independent genetic screenings to explore whether ARGs are already present in the meconium accumulated in the GIT during fetal life and in feces of 1-week-old infants. We have analyzed resistance to β-lactam antibiotics (BLr) and tetracycline (Tcr), screening...... fecal samples and colostrum. Our results reveal a high prevalence of BLr and Tcr in both meconium and early fecal samples, implying that the GIT resistance reservoir starts to accumulate even before birth. We show that ARGs present in the mother may reach the meconium and colostrum and establish...

  6. Esterase polymorphism in remanant populations of Aspidosperma polyneuron Müll.Arg. (Apocynaceae Polimorfismo de esterases em populações remanescentes de Aspidosperma polyneuron Müll.Arg. (Apocynaceae

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    Vanda Marilza de Carvalho

    2004-10-01

    Full Text Available The population genetic structure of the endangered tree species Aspidosperma polyneuron Mull.Arg. (Apocynaceae was reported based on analysis of esterase polymorphism in two remanant populations. Allelic variation was detected at three isoesterase loci (Est-3, Est-9, and Est-10. The proportion of polymorphic loci for both populations was 30% and deviation from Hardy-Weinberg equilibrium was observed for the Est-3 locus observed in the northern population. Segregation distortion and the lower level of observed and expected heterozygosity in this population were attributed to founder genotype. The high genetic identity values for northern and northwestern populations are in accordance with the low levels of interpopulation genetic divergence demonstrated by the F(ST (0.03 value. The F(IS value (0.23 indicated moderate levels of inbreeding. A. polyneuron can be indicated as an example of endangered species suggesting high genetic variation in contrast to the low genetic variation reported for endangered species. The esterase isozymes may be a good genetic marker for studies of natural A. polyneuron populations.A análise do polimorfismo de isozimas esterases foi usada para reportar a estrutura genética de duas populações remanecentes da espécie de árvore em extinção Aspidosperma polyneuron Müll.Arg. (Apocynaceae. Variação alélica foi detectada em três locos de isoesterases (Est-3, Est-9, e Est-10. A proporção de locos polimórficos de ambas as populações foi de 30%, sendo observado um desvio do equilíbrio de Hardy-Weinberg no loco Est-3 na população da região norte do Estado do Paraná. Uma distorção na segregação e um mais baixo nível de heterozigosidade observada e esperada nesta população foram atribuídos ao efeito do genótipo fundador. Os valores altos de identidade genética das populações do norte e noroeste do Estado estão de acordo com o baixo nível de divergência genética interpopulacional demonstrado

  7. Comparative metagenomics reveals a diverse range of antimicrobial resistance genes in effluents entering a river catchment.

    Science.gov (United States)

    Rowe, Will; Verner-Jeffreys, David W; Baker-Austin, Craig; Ryan, Jim J; Maskell, Duncan J; Pearce, Gareth P

    2016-01-01

    The aquatic environment has been implicated as a reservoir for antimicrobial resistance genes (ARGs). In order to identify sources that are contributing to these gene reservoirs, it is crucial to assess effluents that are entering the aquatic environment. Here we describe a metagenomic assessment for two types of effluent entering a river catchment. We investigated the diversity and abundance of resistance genes, mobile genetic elements (MGEs) and pathogenic bacteria. Findings were normalised to a background sample of river source water. Our results show that effluent contributed an array of genes to the river catchment, the most abundant being tetracycline resistance genes tetC and tetW from farm effluents and the sulfonamide resistance gene sul2 from wastewater treatment plant (WWTP) effluents. In nine separate samples taken across 3 years, we found 53 different genes conferring resistance to seven classes of antimicrobial. Compared to the background sample taken up river from effluent entry, the average abundance of genes was three times greater in the farm effluent and two times greater in the WWTP effluent. We conclude that effluents disperse ARGs, MGEs and pathogenic bacteria within a river catchment, thereby contributing to environmental reservoirs of ARGs.

  8. The MECP2 variant c.925C>T (p.Arg309Trp) causes intellectual disability in both males and females without classic features of Rett syndrome.

    Science.gov (United States)

    Schönewolf-Greulich, B; Tejada, M-I; Stephens, K; Hadzsiev, K; Gauthier, J; Brøndum-Nielsen, K; Pfundt, R; Ravn, K; Maortua, H; Gener, B; Martínez-Bouzas, C; Piton, A; Rouleau, G; Clayton-Smith, J; Kleefstra, T; Bisgaard, A-M; Tümer, Z

    2016-06-01

    Missense MECP2 variants can have various phenotypic effects ranging from a normal phenotype to typical Rett syndrome (RTT). In females, the phenotype can also be influenced by the X-inactivation pattern. In this study, we present detailed clinical descriptions of six patients with a rare base-pair substitution affecting Arg309 at the C-terminal end of the transcriptional repression domain (TRD). All patients have intellectual disability and present with some RTT features, but they do not fulfill the clinical criteria for typical or atypical RTT. Most of the patients also have mild facial dysmorphism. Intriguingly, the mother of an affected male patient is an asymptomatic carrier of this variant. It is therefore likely that the p.(Arg309Trp) variation does not necessarily lead to male lethality, and it results in a wide range of clinical features in females, probably influenced by different X-inactivation patterns in target tissues.

  9. Utilización de otros láseres en odontología: Argón, Nd:YAP y Ho:YAG

    OpenAIRE

    Guinot Moya, Rosa; España Tost, A. J. (Antonio Jesús); Berini Aytés, Leonardo; Gay Escoda, Cosme

    2004-01-01

    Las ventajas que la incorporación del láser ha proporcionado a la Odontología abarcan todos los ámbitos. Así, los láseres de Argón, de Nd:YAP y de Ho:YAG, tienen aplicaciones muy concretas y de gran interés tanto en el campo de la terapéutica dental como en la especialida de cirugía bucal. Las aplicaciones principales del láser de Argón se centran en la polimerización de los materiales de restauración, en la endodoncia y dentro del ámbito de la cirugía bucal, en el corte de tejidos blandos, p...

  10. Antibiotics, Antibiotic Resistance Genes, and Bacterial Community Composition in Fresh Water Aquaculture Environment in China.

    Science.gov (United States)

    Xiong, Wenguang; Sun, Yongxue; Zhang, Tong; Ding, Xueyao; Li, Yafei; Wang, Mianzhi; Zeng, Zhenling

    2015-08-01

    Environmental antibiotic resistance has drawn increasing attention due to its great threat to human health. In this study, we investigated concentrations of antibiotics (tetracyclines, sulfonamides and (fluoro)quinolones) and abundances of antibiotic resistance genes (ARGs), including tetracycline resistance genes, sulfonamide resistance genes, and plasmid-mediated quinolone resistance genes, and analyzed bacterial community composition in aquaculture environment in Guangdong, China. The concentrations of sulfametoxydiazine, sulfamethazine, sulfamethoxazole, oxytetracycline, chlorotetracycline, doxycycline, ciprofloxacin, norfloxacin, and enrofloxacin were as high as 446 μg kg(-1) and 98.6 ng L(-1) in sediment and water samples, respectively. The relative abundances (ARG copies/16S ribosomal RNA (rRNA) gene copies) of ARGs (sul1, sul2, sul3, tetM, tetO, tetW, tetS, tetQ, tetX, tetB/P, qepA, oqxA, oqxB, aac(6')-Ib, and qnrS) were as high as 2.8 × 10(-2). The dominant phyla were Proteobacteria, Bacteroidetes, and Firmicutes in sediment samples and Proteobacteria, Actinobacteria and Bacteroidetes in water samples. The genera associated with pathogens were also observed, such as Acinetobacter, Arcobacter, and Clostridium. This study comprehensively investigated antibiotics, ARGs, and bacterial community composition in aquaculture environment in China. The results indicated that fish ponds are reservoirs of ARGs and the presence of potential resistant and pathogen-associated taxonomic groups in fish ponds might imply the potential risk to human health.

  11. Lack of evidence of HPV etiology of prostate cancer following radical surgery and higher frequency of the Arg/Pro genotype in turkish men with prostate cancer

    Science.gov (United States)

    Aydin, Merve; Bozkurt, Aliseydi; Cikman, Aytekin; Gulhan, Baris; Karabakan, Mehmet; Gokce, Aysun; Alper, Murat; Kara, Murat

    2017-01-01

    ABSTRACT Objectives The aim of this study was to assess the possible role of HPV in the development of prostate cancer (PCa) and investigate the distribution of the p53 codon 72 polymorphism in PCa in a Turkish population. Materials and methods A total of 96 tissues, which had been obtained using a radical surgery method, formalin-fixed and parafin-embedded, were used in this study. The study group consisted of 60 PCa tissues (open radical prostatectomy) and the control group contained 36 benign prostatic hyperplasia tissues (BPH) (transvesical open prostatectomy). The presence of HPV and the p53 codon 72 polymorphism was investigated in both groups using real-time PCR and pyrosequencing. Results The results of the real-time PCR showed no HPV DNA in any of the 36 BPH tissue samples. HPV-DNA was positive in only 1 of the 60 PCa samples (1.7%). The HPV type of this sample was identified as HPV-57. The distribution of the three genotypes, Arg/Arg, Arg/Pro and Pro/Pro was found to be 45.6, 45.6, and 8.8% in the PCa group and 57.1%, 34.3% and 8.6% in the control group, respectively. Compared with the control group, patients with PCa had a higher frequency of the Arg/Pro genotype and Proline allele (odds ratio (OR)=1.67, 95% confidence interval (CI)=0.68-4.09, p=0.044; OR=1.13, 95% CI=0.76-1.68, p=0.021, respectively). Conclusions The results of the study do not support the hyphothesis that prostate cancer is associated with HPV infection but indicated that Proline allele can be a risk factor in the development of PCa in the Turkish population. PMID:28124524

  12. Lack of evidence of HPV etiology of prostate cancer following radical surgery and higher frequency of the Arg/Pro genotype in turkish men with prostate cancer

    Directory of Open Access Journals (Sweden)

    Merve Aydin

    Full Text Available ABSTRACT Objectives The aim of this study was to assess the possible role of HPV in the development of prostate cancer (PCa and investigate the distribution of the p53 codon 72 polymorphism in PCa in a Turkish population. Materials and methods A total of 96 tissues, which had been obtained using a radical surgery method, formalin-fixed and parafin-embedded, were used in this study. The study group consisted of 60 PCa tissues (open radical prostatectomy and the control group contained 36 benign prostatic hyperplasia tissues (BPH (transvesical open prostatectomy. The presence of HPV and the p53 codon 72 polymorphism was investigated in both groups using real-time PCR and pyrosequencing. Results The results of the real-time PCR showed no HPV DNA in any of the 36 BPH tissue samples. HPV-DNA was positive in only 1 of the 60 PCa samples (1.7%. The HPV type of this sample was identified as HPV-57. The distribution of the three genotypes, Arg/Arg, Arg/Pro and Pro/Pro was found to be 45.6, 45.6, and 8.8% in the PCa group and 57.1%, 34.3% and 8.6% in the control group, respectively. Compared with the control group, patients with PCa had a higher frequency of the Arg/Pro genotype and Proline allele (odds ratio (OR=1.67, 95% confidence interval (CI=0.68-4.09, p=0.044; OR=1.13, 95% CI=0.76-1.68, p=0.021, respectively. Conclusions The results of the study do not support the hyphothesis that prostate cancer is associated with HPV infection but indicated that Proline allele can be a risk factor in the development of PCa in the Turkish population.

  13. Role of Arg228 in the phosphorylation of galactokinase: the mechanism of GHMP kinases by quantum mechanics/molecular mechanics studies.

    Science.gov (United States)

    Huang, Meilan; Li, Xiaozhou; Zou, Jian-Wei; Timson, David J

    2013-07-16

    GHMP kinases are a group of structurally related small molecule kinases. They have been found in all kingdoms of life and are mostly responsible for catalyzing the ATP-dependent phosphorylation of intermediary metabolites. Although the GHMP kinases are of clinical, pharmaceutical, and biotechnological importance, the mechanism of GHMP kinases is controversial. A catalytic base mechanism was suggested for mevalonate kinase that has a structural feature of the γ-phosphate of ATP close to an aspartate residue; however, for one GHMP family member, homoserine kinase, where the residue acting as general base is absent, a direct phosphorylation mechanism was suggested. Furthermore, it was proposed by some authors that all the GHMP kinases function by a similar mechanism. This controversy in mechanism has limited our ability to exploit these enzymes as drug targets and in biotechnology. Here the phosphorylation reaction mechanism of the human galactokinase, a member of the GHMP kinase family, was investigated using molecular dynamics simulations and density functional theory-based quantum mechanics/molecular mechanics calculations (B3LYP-D/AMBER99). The reaction coordinates were localized by potential energy scan using an adiabatic mapping method. Our results indicate that a highly conserved Glu174 captures Arg105 in the proximity of the α-phosphate of ATP, forming a H-bond network; therefore, the mobility of ATP in the large oxyanion hole is restricted. Arg228 functions to stabilize the negative charge developed at the β,γ-bridging oxygen of the ATP during bond cleavage. The reaction occurs via a direct phosphorylation mechanism, and the Asp186 in the proximity of ATP does not directly participate in the reaction pathway. Because Arg228 is not conserved among GHMP kinases, reagents which form interactions with Arg228, and therefore can interrupt its function in phosphorylation, may be developed into potential selective inhibitors for galactokinase.

  14. Distribution of tetracycline resistance genes and AmpC β-lactamase genes in representative non-urban sewage plants and correlations with treatment processes and heavy metals.

    Science.gov (United States)

    Xu, Yan-Bin; Hou, Mao-Yu; Li, Ya-Fei; Huang, Lu; Ruan, Jing-Jing; Zheng, Li; Qiao, Qing-Xia; Du, Qing-Ping

    2017-03-01

    The mixed development of livestock breeding and industry in non-urban zones is a very general phenomenon in China. Distribution of antibiotic resistance genes (ARGs) in non-urban sewage treatment systems has not been paid enough attentions. In this study, eleven tetracycline resistance genes (tetA, tetB, tetC, tetE, tetG, tetL, tetM, tetO, tetQ, tetS and tetX), four AmpC β-lactamase genes (EBC, MOX, FOX and CIT) and four heavy metals (Cu, Zn, Cd and Pb) were detected and analyzed in four non-urban sewage plants with different sewage sources and different treatment processes in Guangzhou. The results showed that tetA and tetC were the most prevalent tetracycline resistance genes with the same detection frequency of 85% and EBC was the most prevalent AmpC β-lactamase gene with a detection frequency of 75%. The relative abundance of tetracycline resistance genes was approximately 1.6 orders of magnitudes higher than that of AmpC β-lactamase genes in all samples. A/O was the most effective process for the non-urban sewage plant receiving industrial or agricultural wastewater. Sedimentation was the most key process to eliminate ARGs from liquid phase. Most ARGs were carried in excess sludge rather than effluent. Significant correlation was found between the tet gene and Zn (r = 0.881, p pollution of ARGs in the sewage treatment systems of non-urban zones co-polluted by heavy metals should be paid more attentions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Expression of FOXP3, CD14, and ARG1 in Neuroblastoma Tumor Tissue from High-Risk Patients Predicts Event-Free and Overall Survival

    Directory of Open Access Journals (Sweden)

    Sara Stigliani

    2015-01-01

    Full Text Available The prognosis of children with metastatic neuroblastoma (NB > 18 months at diagnosis is dismal. Since the immune status of the tumor microenvironment could play a role in the history of disease, we evaluated the expression of CD45, CD14, ARG1, CD163, CD4, FOXP3, Perforin-1 (PRF1, Granzyme B (GRMB, and IL-10 mRNAs in primary tumors at diagnosis from children with metastatic NB and tested whether the transcript levels are significantly associated to event-free and overall survival (EFS and OS, resp.. Children with high expression of CD14, ARG1 and FOXP3 mRNA in their primary tumors had significantly better EFS. Elevated expression of CD14, and FOXP3 mRNA was significantly associated to better OS. CD14 mRNA expression levels significantly correlated to all markers, with the exception of CD4. Strong positive correlations were found between PRF1 and CD163, as well as between PFR1 and FOXP3. It is worth noting that the combination of high levels of CD14, FOXP3, and ARG1 mRNAs identified a small group of patients with excellent EFS and OS, whereas low levels of CD14 were sufficient to identify patients with dismal survival. Thus, the immune status of the primary tumors of high-risk NB patients may influence the natural history of this pediatric cancer.

  16. Identification of proteinaceous inhibitors of a cysteine proteinase (an Arg-specific gingipain) from Porphyromonas gingivalis in rice grain, using targeted-proteomics approaches.

    Science.gov (United States)

    Taiyoji, Mayumi; Shitomi, Yasuyuki; Taniguchi, Masayuki; Saitoh, Eiichi; Ohtsubo, Sadami

    2009-11-01

    Porphyromonas gingivalis is known to be a major etiologic agent in the onset and progression of chronic periodontitis. Among various virulence factors that this bacterium produces, Arg- and Lys-specific cysteine proteinases (gingipains) are believed to be major determinants of the pathogenicity of P. gingivalis. Here, we report on our finding that there are inhibitors of these cysteine proteinases in a rice protein fraction. Comprehensive affinity chromatography and MS analyses resulted in the identification of 17 Arg-gingipain (Rgp)-interacting proteins in the rice endosperm. Of these, four proteins (i.e., a 26 kDa globulin, a plant lipid transfer/trypsin-alpha amylase inhibitor, the RA17 seed allergen, and an alpha amylase/trypsin inhibitor) were estimated to account for 90% of the Rgp inhibitory activity in the rice protein fraction, using a two-dimensional gel system of double-layer reverse zymography. In addition, a synthetic peptide derived from an Rgp-interacting protein, cyanate hydratase, could inhibit the growth of P. gingivalis and showed inhibitory activity against both the Arg- and Lys-gingipains. These results suggest that these rice proteins may be useful as nutraceutical ingredients for the prevention and management of periodontal diseases.

  17. Arg-gly-asp-mannose-6-phosphate inhibits activation and proliferation of hepatic stellate cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Lian-Sheng Wang; Ying-Wei Chen; Ding-Guo Li; Han-Ming Lu

    2006-01-01

    AIM: To investigate the effect of arg-gly-asp-mannose-6phosphate (RGD-M6P) on the activation and proliferation of primary hepatic stellate cells in vitro.METHODS: Hepatic stellate cells (HSCs) were isolated from rats by in situ collagenase perfusion of liver and 18% Nycodenz gradient centrifugation and cultured on uncoated plastic plates for 24 h with DMEM containing 10% fetal bovine serum (FBS/DMEM) before the culture medium was substituted with 2% FBS/DMEM for another 24 h. Then, HSCs were cultured in 2% FBS/DMEM with transforming growth factor β1, M6P, RGD, or RGD-M6P, respectively. Cell morphology was observed under inverted microscope, smooth muscle α-actin (α-SMA)was detected by immunocytochemistry, type Ⅲprocollagen (PCⅢ) in supernatant was determined by radioimmunoassay, and the proliferation rate of HSCs was assessed by flow cytometry.RESULTS: RGD-M6P significantly inhibited the morphological transformation and the α-SMA and PC Ⅲ expressions of HSCs in vitro and also dramatically prevented the proliferation of HSCs in vitro. Such effects were remarkably different from those of RGD or M6P.CONCLUSION: The new compound, RGD-M6P, which has a dramatic effect on primary cultured HSCs in vitro, can inhibit the transformation of HSCs in culture caused by TGFβ1, suppresses the expression of PCⅢand decreases proliferation rate of HSC. RGD-M6P can be applied as a selective drug carrier targeting at HSCs,which may be a new approach to the prevention and treatment of liver fibrosis.

  18. The diversity of the HLA-E-restricted peptide repertoire explains the immunological impact of the Arg107Gly mismatch.

    Science.gov (United States)

    Celik, Alexander A; Kraemer, Thomas; Huyton, Trevor; Blasczyk, Rainer; Bade-Döding, Christina

    2016-01-01

    Human leukocyte antigen (HLA)-E molecules are potent inhibitors of NK cell-mediated killing. Low in polymorphisms, two alleles are widely expressed among diverse populations: HLA-E*01:01 and HLA-E*01:03. Both alleles are distinguished by one SNP resulting in the substitution Arg107Gly. Both alleles present a limited set of peptides derived from class I leader sequences physiologically; however, HLA-E*01:01 presents non-canonical peptides in the absence of HLA class I molecules. To further assess the functional differences between both alleles, we analyzed the peptide repertoire of HLA-E*01:03 by applying soluble HLA technology followed by mass-spectrometric peptide sequencing. HLA-E*01:03 restricted peptides showed a length of 9-17 amino acids and differed in their biophysical properties, no overlap in the peptide repertoire of both allelic variants could be observed; however, both alleles shared marginal peptides from the same proteomic content. Artificial APCs expressing empty HLA-E*01:01 or E*01:03 molecules were generated and stabilized using cognate HLA class I-derived peptide ligands to analyze the impact of residue 107 within the HLA-E heavy chain on the NKG2/CD94 receptor engagement. Differences in peptide stabilization could be translated to the density and half-life time of peptide-HLA-E molecules on the cell surface that subsequently impacted NK cell inhibition as verified by cytotoxicity assays. Taken together, these data illustrate functional differences of HLA-E allelic variants induced by a single amino acid. Furthermore, the function of HLA-E in pathophysiologic situations when the HLA processing machinery is interrupted seems to be more emphasized than previously described, implying a crucial role for HLA-E in tumor or viral immune episodes.

  19. Effects of Condensed Tannins in Mao ( Muell. Arg. Seed Meal on Rumen Fermentation Characteristics and Nitrogen Utilization in Goats

    Directory of Open Access Journals (Sweden)

    P. Gunun

    2016-08-01

    Full Text Available Mao seed is a by-product of the wine and juice industry, which could be used in animal nutrition. The current study was designed to determine the effect of supplementation of mao (Antidesma thwaitesianum Muell. Arg. seed meal (MOSM containing condensed tannins (CT on rumen fermentation, nitrogen (N utilization and microbial protein synthesis in goats. Four crossbred (Thai Native×Anglo Nubian goats with initial body weight (BW 20±2 kg were randomly assigned to a 4×4 Latin square design. The four dietary treatments were MOSM supplementation at 0%, 0.8%, 1.6%, and 2.4% of total dry matter (DM intake, respectively. During the experimental periods, all goats were fed a diet containing roughage to concentrate ratio of 60:40 at 3.0% BW/d and pangola grass hay was used as a roughage source. Results showed that supplementation with MOSM did not affect feed intake, nutrient intakes and apparent nutrient digestibility (p>0.05. In addition, ruminal pH and ammonia nitrogen (NH3-N were not influenced by MOSM supplementation, whilst blood urea nitrogen was decreased quadraticly (p0.05. There were linear decreases in urinary N (p0.05. From the current study, it can be concluded that supplementation of MOSM at 1.6% to 2.4% of total DM intake can be used to modify ruminal fermentation, especially propionate and N utilization in goats, without affecting the nutrient digestibility, microbial populations and microbial protein synthesis.

  20. Pharmacological evaluation of Mallotus philippinensis (Lam. Muell.-Arg. fruit hair extract for Anti-Inflammatory, Analgesic and Hypnotic Activity

    Directory of Open Access Journals (Sweden)

    Mayank Gangwar

    2016-03-01

    Full Text Available Recently we observed wound healing activity of 50% ethanol extract of Mallotus philippinensis Muell. Arg (MP fruit hairs extract (MPE. In several intestinal infections, localized inflammation is of common occurrence and hence we evaluated the anti-inflammatory, analgesic and hypnotic activity of MPE in different rat experimental models. Anti-inflammatory activity was evaluated by carrageenan (acute and turpentine oil induced formalin (subacute induced paw oedema and while, granuloma pouch (subacute in rats. Analgesic and hypnotic activity of MPE was undertaken by tail-flick, hot and ndash;plate and acetic acid-induced writhing tests while pentobarbitone-induced hypnotic potentiation respectively in rats.\tMPE at a dose of 200 mg/kg at 3 hr after their administration showed inhibition of formalin-induced paw oedema by 41.60% (P<0.001 and carrageenan-induced paw oedema by 55.30% (P<0.001. After 7 days of treatments, MPE showed 38.0% (P<0.001 inhibition against formalin-induced paw oedema and reduced weight of turpentine-induced granuloma pouch by 29.6% (P<0.01 and volume of exudates by 26.1% (P<0.01 respectively. MPE (200 mg/kg showed dose-dependent elevation in pain threshold and peak analgesic effect at 120 min as evidenced by increased latency period in tail flick method and increased reaction time in hot-plate test while reduction in the number of acetic acid-induced writhes by 45.7% (P<0.001. The pentobarbitone-induced hypnosis model showed potentiation, as defined by increased duration of sleep in treated group rats as compared to control. Thus, the study revealed MPE is effective in reducing acute and sub-acute inflammation and showed effective and similar analgesic activity. This seemed to be safe in the treatment of pain and inflammation. [J Intercult Ethnopharmacol 2016; 5(1.000: 14-21

  1. H{sub 2}O{sub 2} and/or TiO{sub 2} photocatalysis under UV irradiation for the removal of antibiotic resistant bacteria and their antibiotic resistance genes

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Changsheng [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Wang, Kai [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Wuxi SensingNet Industrialization Research Institute, Wuxi 214000 (China); Hou, Song; Wan, Li; Lv, Jiapei; Zhang, Yuan [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Qu, Xiaodong [State Key Laboratory of Simulation and Regulation of Water Cycle in River Basin, and Department of Water Environment, China Institute of Water Resources and Hydropower Research, Beijing 100038 (China); Chen, Shuyi [Wuxi SensingNet Industrialization Research Institute, Wuxi 214000 (China); Xu, Jian, E-mail: xujian@craes.org.cn [State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China)

    2017-02-05

    Highlights: • TiO{sub 2} thin film was successfully synthesized for treating ARB and ARGs from water. • More than 5.5 log units of ARB reduction was achieved by TiO{sub 2} under UV irradiation. • With TiO{sub 2}, ARGs were reduced by more than 5 log units under UV irradiation. • TiO{sub 2} could remove both intracellular and extracellular forms of ARGs. - Abstract: Inactivating antibiotic resistant bacteria (ARB) and removing antibiotic resistance genes (ARGs) are very important to prevent their spread into the environment. Previous efforts have been taken to eliminate ARB and ARGs from aqueous solution and sludges, however, few satisfying results have been obtained. This study investigated whether photocatalysis by TiO{sub 2} was able to reduce the two ARGs, mecA and ampC, within the host ARB, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, respectively. The addition of H{sub 2}O{sub 2} and matrix effect on the removal of ARB and ARGs were also studied. TiO{sub 2} thin films showed great effect on both ARB inactivation and ARGs removal. Approximately 4.5-5.0 and 5.5–5.8 log ARB reductions were achieved by TiO{sub 2} under 6 and 12 mJ/cm{sup 2} UV{sub 254} fluence dose, respectively. For ARGs, 5.8 log mecA reduction and 4.7 log ampC reduction were achieved under 120 mJ/cm{sup 2} UV{sub 254} fluence dose in the presence of TiO{sub 2}. Increasing dosage of H{sub 2}O{sub 2} enhanced the removal efficiencies of ARB and ARGs. The results also demonstrated that photocatalysis by TiO{sub 2} was capable of removing both intracellular and extracellular forms of ARGs. This study provided a potential alternative method for the removal of ARB and ARGs from aqueous solution.

  2. Class 1 integrase, sulfonamide and tetracycline resistance genes in wastewater treatment plant and surface water.

    Science.gov (United States)

    Makowska, Nicoletta; Koczura, Ryszard; Mokracka, Joanna

    2016-02-01

    Wastewater treatment plants are considered hot spots for multiplication and dissemination of antibiotic-resistant bacteria and resistance genes. In this study, we determined the presence of class 1 integron integrase and genes conferring resistance to tetracyclines and sulfonamides in the genomes of culturable bacteria isolated from a wastewater treatment plant and the river that receives the treated wastewater. Moreover, using PCR-based metagenomic approach, we quantified intI1, tet and sul genes. Wastewater treatment caused the decrease in the total number of culturable heterotrophs and bacteria resistant to tetracycline and sulfonamides, along with the decrease in the number of intI1, sul and tet gene copies per ml, with significant reduction of tet(B). On the other hand, the treatment process increased both the frequency of tetracycline- and sulfonamide-resistant bacteria and intI1-positive strains, and the relative abundance of all quantified antibiotic resistance genes (ARGs) and intI1 gene; in the case of tet(A) and sul2 significantly. The discharge of treated wastewater increased the number of intI1, tet and sul genes in the receiving river water both in terms of copy number per ml and relative abundance. Hence, despite the reduction of the number of ARGs and ARBs, wastewater treatment selects for bacteria with ARGs in effluent.

  3. High-throughput quantification of antibiotic resistance genes from an urban wastewater treatment plant.

    Science.gov (United States)

    Karkman, Antti; Johnson, Timothy A; Lyra, Christina; Stedtfeld, Robert D; Tamminen, Manu; Tiedje, James M; Virta, Marko

    2016-03-01

    Antibiotic resistance among bacteria is a growing problem worldwide, and wastewater treatment plants have been considered as one of the major contributors to the dissemination of antibiotic resistance to the environment. There is a lack of comprehensive quantitative molecular data on extensive numbers of antibiotic resistance genes (ARGs) in different seasons with a sampling strategy that would cover both incoming and outgoing water together with the excess sludge that is removed from the process. In order to fill that gap we present a highly parallel quantitative analysis of ARGs and horizontal gene transfer potential over four seasons at an urban wastewater treatment plant using a high-throughput qPCR array. All analysed transposases and two-thirds of primer sets targeting ARGs were detected in the wastewater. The relative abundance of most of the genes was highest in influent and lower in effluent water and sludge. The resistance profiles of the samples cluster by sample location with a shift from raw influent through the final effluents and dried sludge to the sediments. Wastewater discharge enriched only a few genes, namely Tn25 type transposase gene and clinical class 1 integrons, in the sediment near the discharge pipe, but those enriched genes may indicate a potential for horizontal gene transfer.

  4. Features of Localization of ARG-X Protease-processing in the Suprastructures of Interphase Chromatin under Conditions of Cell Cycle Arrest by Sodium Butyrate, upon Induction of Growth Morphogenesis of Mature Embryos of Winter and Spring Wheat

    Directory of Open Access Journals (Sweden)

    Ivanov R.S.

    2016-08-01

    Full Text Available A fundamental property of many organisms is the ability to feel, to assess direction of the signal action and respond to the environmental conditions. It is known that chromatin plays a major role in organizing the regulation of gene activity. However, our understanding of how state of the suprastructure organization of chromatin and its proteins reacts not only to changes in the environment, but also on the development of specific signals remains largely unclear. In the course of this work, we have analyzed the result of the various ways of chromatin modifications: the regulatory Arg-X protease-processing and inhibition of protein deacetylation with sodium butyrate. Sodium butyrate causes cell cycle arrest in the G0/G1 phase, and promotes of duration of the transcriptional activity of chromatin. Experiments on molecular-genetic state of the chromatin matrix were carried out at the induction of growth morphogenesis in the physiological period of active water absorption of mature seeds and wheat germs, which were purposefully transformed and formed in different environmental conditions. During focused, long-term transforming of spring wheat Artemovka into winter wheat Mironovskaya 808 and the last of them again into Mironovskaya Spring wheat while stopping of the cell cycle in the G0/G1 phase, mainly occurs the active Arg-X protease-processing at the level of non-histone proteins, and linker histones of suprastructures chromatin. We assume that the regulatory proteolytic processing and prolongation of acetylation of proteins can be interconnected in the regulation of conformational transitions of chromatin at the different levels of its organization: both suprastructures and at the more profound proteomic level of non-histone and histone blocks, and have its peculiarities during the period of transcriptional activation. We hope that the study peculiarities of locations of regulatory proteolysis in the conditions of inhibition of deacetylation in

  5. Sulfotransferase SULT1A1 Arg213His polymorphism with cancer risk: a meta-analysis of 53 case-control studies.

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    Juanjuan Xiao

    Full Text Available BACKGROUND: The SULT1A1 Arg213His (rs9282861 polymorphism is reported to be associated with many kinds of cancer risk. However, the findings are conflicting. For better understanding this SNP site and cancer risk, we summarized available data and performed this meta-analysis. METHODS: Data were collected from the following electronic databases: PubMed, Web of Knowledge and CNKI. The association was assessed by odd ratio (OR and the corresponding 95% confidence interval (95% CI. RESULTS: A total of 53 studies including 16733 cancer patients and 23334 controls based on the search criteria were analyzed. Overall, we found SULT1A1 Arg213His polymorphism can increase cancer risk under heterozygous (OR  1.09, 95% CI = 1.01-1.18, P = 0.040, dominant (OR = 1.10, 95% CI = 1.01-1.19, P = 0.021 and allelic (OR = 1.08, 95% CI = 1.02-1.16, P = 0.015 models. In subgroup analyses, significant associations were observed in upper aero digestive tract (UADT cancer (heterozygous model: OR = 1.62, 95% CI = 1.11-2.35, P = 0.012; dominant model: OR = 1.63, 95% CI = 1.13-2.35, P = 0.009; allelic model: OR = 1.52, 95% CI = 1.10-2.11, P = 0.012 and Indians (recessive model: OR = 1.93, 95% CI = 1.22-3.07, P = 0.005 subgroups. Hospital based study also showed marginally significant association. In the breast cancer subgroup, ethnicity and publication year revealed by meta-regression analysis and one study found by sensitivity analysis were the main sources of heterogeneity. The association between SULT1A1 Arg213His and breast cancer risk was not significant. No publication bias was detected. CONCLUSIONS: The present meta-analysis suggests that SULT1A1 Arg213His polymorphism plays an important role in carcinogenesis, which may be a genetic factor affecting individual susceptibility to UADT cancer. SULT1A1 Arg213His didn't show any association with breast cancer, but the possible risk in Asian population needs further investigation.

  6. Combined analysis of pri-miR-34b/c rs4938723 and TP53 Arg72Pro with cervical cancer risk.

    Science.gov (United States)

    Yuan, Fang; Sun, Ruifen; Chen, Peng; Liang, Yundan; Ni, Shanshan; Quan, Yi; Huang, Juan; Zhang, Lin; Gao, Linbo

    2016-05-01

    miR-34 family members can form a p53-miR-34 positive feedback loop and induce apoptosis, DNA repair, angiogenesis, and cell cycle arrest. We conducted a case-control study to examine whether two polymorphisms (i.e., rs4938723 in the promoter of pri-miR-34b/c and TP53 Arg72Pro) were linked to the carcinogenesis of cervical cancer among Chinese Han women. Genotypes of the two polymorphisms in 328 cervical cancer patients and 568 control subjects were determined by using a polymerase chain reaction-restriction fragment length polymorphism assay. We found a significantly increased cervical cancer risk in the pri-miR-34b/c rs4938723 under dominant and overdominant model (CT/CC vs. TT: adjusted OR = 1.34, 95 % CI = 1.01-1.77; CT vs. TT/CC: adjusted OR = 1.37, 95 % CI = 1.05-1.80, respectively). Increased cervical cancer risks were also found in the TP53 Arg72Pro under a heterozygous comparison and overdominant model (CG vs. GG: adjusted OR = 1.44, 95 % CI = 1.06-1.95; CG vs. GG/CC: adjusted OR = 1.47, 95 % CI = 1.12-1.94, respectively). Stratification analysis showed that patients carrying the pri-miR-34b/c rs4938723 CT genotype had a significantly increased risk for developing poorly differential status and clinical stage I. Moreover, increased cancer risks were observed for the TP53 Arg72Pro polymorphism in patients with poorly differential status, clinical stage II, and without lymph node metastasis. Combined analysis revealed that the genotypes of rs4938723 CT/CC and TP53 Arg72Pro CG/CC had an increased cervical cancer risk (OR = 2.21, 95 % CI = 1.38-3.53). These findings suggest that the pri-miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms may contribute to the genesis of cervical cancer.

  7. Elevated ARG1 expression in primary monocytes-derived macrophages as a predictor of radiation-induced acute skin toxicities in early breast cancer patients.

    Science.gov (United States)

    Jung, Karen; Sabri, Siham; Hanson, John; Xu, Yaoxian; Wang, Ying Wayne; Lai, Raymond; Abdulkarim, Bassam S

    2015-01-01

    Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines before quantitative analysis of their "M1/M2" activation markers, iNOS, Arg1, and TGFß1. Statistical analysis was performed to correlate experimental data to clinical assessment of acute skin toxicity using Common Toxicity Criteria (CTC) grade for objective evaluation of skin reactions. Increased ARG1 mRNA significantly correlated with higher grades of erythema, moist desquamation, and CTC grade. Multivariate analysis revealed that increased ARG1 expression in macrophages after a single RT dose was an independent prognostic factor of erythema (p = 0 .032), moist desquamation (p = 0 .027), and CTC grade (p = 0 .056). Interestingly, multivariate analysis of ARG1 mRNA expression in macrophages stimulated with IL-4 also revealed independent prognostic value for predicting acute RT-induced toxicity factors, erythema (p = 0 .069), moist desquamation (p = 0 .037), and CTC grade (p = 0 .046). To conclude, our findings underline for the first time the biological significance of increased ARG1 m

  8. Pyridoxine responsiveness in novel mutations of the PNPO gene

    OpenAIRE

    2014-01-01

    OBJECTIVE: To determine whether patients with pyridoxine-responsive seizures but normal biomarkers for antiquitin deficiency and normal sequencing of the ALDH7A1 gene may have PNPO mutations. METHODS: We sequenced the PNPO