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Sample records for m1 genotype affects

  1. Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer.

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    Yan, Shushan; Wang, Zengfang; Wang, Zengyan; Duan, Quanhong; Wang, Xiaochen; Li, Jun; Sun, Beicheng

    2016-08-01

    Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.

  2. Indication for joint replacement and glutathione s-transferases M1 and T1 genotypes.

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    Klein, Torsten; Selinski, Silvia; Blaszkewicz, Meinolf; Hengstler, Jan G; Golka, Klaus

    2012-01-01

    In most patients with osteoarthritis (OA), therapy-resistant pain is the indication for hip or knee replacement. Glutathione S-transferases, particularly glutathione S-transferase M1 (GSTM1), are involved in metabolism of highly reactive metabolites that may be generated by inflammatory processes. In total, 148 patients with indication for hip or knee replacement and 129 patients of the same hospital without indication for joint replacement were genotyped for GSTM1 and GSTT1 and interviewed by a newly developed questionnaire for occupational and nonoccupational risk factors of hip and/or knee osteoarthritis. Mean age was 70.9 yr in OA cases and 67.4 yr in controls. The frequency of GSTM1 negative in the OA case group was (45%) in the lower range compared to values in Caucasian general population (approximately 50%), whereas the frequency in the controls was normal (51%). The frequency of GSTT1 negative genotype in OA cases and controls was normal. The normal distribution of the GSTM1 negative genotype in patients with indication for hip or knee replacement indicates that the role GSTM1 in these patients is different from that in other aseptic inflammatory diseases such as ozone-related inflammatory reactions of the respiratory tract.

  3. Miners compensated for pneumoconiosis and glutathione s-transferases M1 and T1 genotypes.

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    Zimmermann, Anna; Ebbinghaus, Rainer; Prager, Hans-Martin; Blaszkewicz, Meinolf; Hengstler, Jan G; Golka, Klaus

    2012-01-01

    Chronic inhalation of quartz-containing dust produces reversible inflammatory changes in lungs resulting in irreversible fibrotic changes termed pneumoconiosis. Due to the inflammatory process in the lungs, highly reactive substances are released that may be detoxified by glutathione S-transferases. Therefore, 90 hard coal miners with pneumoconiosis as a recognized occupational disease (in Germany: Berufskrankheit BK 4101) were genotyped for glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) according to standard methods. Furthermore, occupational exposure and smoking habits were assessed by questionnaire. Changes in a chest x-ray were classified according to ILO classification 2000. Of the investigated hard coal miners 43% were GSTM1 negative whereas 57% were GSTM1 positive. The arithmetic mean of the age at time of investigation was 74.2 yr (range: 42-87 yr). Seventy-four percent of the hard coal miners reported being ever smokers, while 26% denied smoking. All hard coal miners provided pneumoconiosis-related changes in the chest x-ray. The observed frequency of GSTM1 negative hard coal miners was not different from frequencies reported for general Caucasian populations and in agreement with findings reported for Chinese coal miners. In contrast, in a former study, 16 of 19 German hard coal miners (84%) with urinary bladder cancer displayed a GSTM1 negative genotype. The outcome of this study provides evidence that severely occupationally exposed Caucasian hard coal miners do not present an elevated level of GSTM1 negative individuals.

  4. Glutathione S-transferase M1 and T1 genotypes and endometriosis risk: a case-controlled study

    Institute of Scientific and Technical Information of China (English)

    林俊; 张信美; 钱羽力; 叶英辉; 石一复; 徐开红; 徐键云

    2003-01-01

    Objective To investigate the correlation between glutathione S-transferase (GST) M1 and T1 genotypes and endometriosis risk (EM). Methods Polymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from the blood samples of 68 Han Chinese women with endometriosis and 28 without endometriosis. Results The frequencies of GSTM1 and GSTT1 null genotypes in women with endometriosis were 0.721 (49/68) and 0.779 (53/68), respectively, and in women without endometriosis were 0.429 (12/28) and 0.321 (9/28), respectively. There was a significant difference with regard to the frequencies of GSTM1 and GSTT1 null genotypes between the women with and without endometriosis (P0.05). Conclusion GSTM1 and GSTT1 null genotypes may be risk factors for the development of endometriosis.

  5. Metabolism of isothiocyanates in individuals with positive and null GSTT1 and M1 genotypes after drinking watercress juice.

    Science.gov (United States)

    Dyba, Marcin; Wang, Antai; Noone, Anne-Michelle; Goerlitz, David; Shields, Peter; Zheng, Yun-Ling; Rivlin, Richard; Chung, Fung-Lung

    2010-12-01

    Isothiocyanates (ITCs) derived from cruciferous vegetables have been shown to be promising agents against cancer in human cell culture, animal models, and in epidemiological studies. Several epidemiological studies have demonstrated an inverse relationship between intake of dietary isothiocyanates and the risk of cancers, particularly lung, colon, and breast. More importantly, the protective effects of dietary ITCs appear to be influenced by glutathione S-transferase (GST) genotype; specifically, individuals with glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase Mu 1 (GSTM1) null are better protected than those with GSTT1 and M1 positive. Although the majority of studies, especially those conducted in populations exposed to ITC rich diets, demonstrated such effects, there are a few studies that showed opposite or no association. While evidence for the interactions of dietary ITCs with GST genes is relatively strong, the reasons for the differential effects remain unclear. In this study, we examined one possible mechanism: whether subjects with null genotypes excrete ITCs at a slower rate than those with positive genotypes after drinking watercress juice, a rich source of ITCs. A total of 48 subjects, 28 GSTT1 and M1 positive and 20 null genotypes were enrolled in the study. The rates of excretion were determined using five urine samples collected over a period of 24 h after drinking watercress juice. No statistically significant differences in the rates of isothiocyanate excretion and the time of peak excretion were observed between the two tested groups having positive and null genotypes. GSTT1 and M1 genotypes are not likely to be involved in the rate of excretion of ITCs in watercress. The demonstrated differences in protection among subjects with the two genotypes are not likely due to differences in overall ITC excretion rates, however, excretion rates of ITCs other than PEITC need to be investigated. Other yet to be identified mechanism

  6. Association between glutathione S-transferase M1 null genotype and risk of gallbladder cancer: a meta-analysis.

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    Sun, Hong-Li; Han, Bing; Zhai, Hong-Peng; Cheng, Xin-Hua; Ma, Kai

    2014-01-01

    Glutathione S-transferases (GSTs) are a family of enzymes which are involved in the detoxification of potential carcinogens. Glutathione S-transferase M1 (GSTM1) null genotype can impair the enzyme activity of GSTs and is suspected to increase the susceptibility to gallbladder cancer. Previous studies investigating the association between GSTM1 null genotype and risk of gallbladder cancer reported inconsistent findings. To quantify the association between GSTM1 null genotype and risk of gallbladder cancer, we performed a meta-analysis of published studies. We searched PubMed, Embase, and Wanfang databases for all possible studies. We estimated the pooled odds ratio (OR) with its 95% confidence interval (95% CI) to assess the association. Meta-analysis of total included studies showed that GSTM1 null genotype was not associated with gallbladder cancer risk (OR = 1.13, 95% CI 0.88-1.46, P = 0.332). Subgroup analysis by ethnicity showed that there was no association between GSTM1 null genotype and risk of gallbladder cancer in both Caucasians and Asians. However, meta-analysis of studies with adjusted estimations showed that GSTM1 null genotype was associated with increased risk of gallbladder cancer (OR = 1.46, 95% CI 1.02-2.09, P = 0.038). Thus, this meta-analysis shows that GSTM1 null genotype is likely to be associated with risk of gallbladder cancer. More studies with well design and large sample size are needed to further validate the association between GSTM1 null genotype and gallbladder cancer.

  7. Glutathione S-transferases M1, T1 genotypes and the risk of gastric cancer: A case-control study

    Institute of Scientific and Technical Information of China (English)

    Lin Cai; Shun-Zhang Yu; Zuo-Feng Zhang

    2001-01-01

    AIM Glutathione S-transferases (GSTs are involved in the detoxification of many potential carcinogens and appear to play a critical role in the protection from the effects of carcinogens. The contribution of glutathione Stransferases M1 and T1 genotypes to susceptibility to the risk of gastric cancer and their interaction with cigarette smoking are still unclear. The aim of this study was to determine whether there was any relationship between genetic polymorphisms of GSTM1 and GSTT1 and gastric cancer. METHODS A population based case - control study was carried out in a high-risk area, Changle County, Fujian Province, China. The epidemiological data were collected by a standard questionnaire and blood samples were obtained from 95 incidence gastric cancer cases and 94 healthy controls. A polymerase chain reaction method was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA. Logistic regression model was employed in the data analysis. RESULTS An increase in risk for gastric cancer was found among carriers of GSTM1 null genotype. The adjusted odds ratio (OR) was 2.63 [95% Confidence Interval (95% CI) 1.17-5.88], after controlling for age,gender, cigarette smoking, alcohol drinking, and fish sauce intake. The frequency of GSTT1 null genotype in cancer cases (43.16%) was not significantly different from that in controls (50.00%). However, the risk for gastric cancer in those with GSTM1 null and GSTT1 nonnull genotype was significantly higher than in those with both GSTM1 and GSTT1 non-null genotype (OR = 2.77,95% Cl 1.15- 6.77). Compared with those subjects who never smoked and had normal GSTM1 genotype, Ors were 1.60 (95% CI: 0.62- 4.19) for never smokers with GSTM1 null type, 2.33 (95% CI 0.88- 6.28) for smokers with normal GSTM1, and 8.06 (95% CI 2.83- 23.67) for smokers with GSTM1 null type. CONCLUSIONS GSTM1 gene polymorphisms may be associated with genetic susceptibility of stomach cancer and may modulate tobacco

  8. Distant and new mutations in CTX-M-1 beta-lactamase affect cefotaxime hydrolysis.

    Science.gov (United States)

    Pérez-Llarena, Francisco José; Kerff, Frédéric; Abián, Olga; Mallo, Susana; Fernández, María Carmen; Galleni, Moreno; Sancho, Javier; Bou, Germán

    2011-09-01

    The CTX-M β-lactamases are an increasingly prevalent group of extended-spectrum β-lactamases (ESBL). Point mutations in CTX-M β-lactamases are considered critical for enhanced hydrolysis of cefotaxime. In order to clarify the structural determinants of the activity against cefotaxime in CTX-M β-lactamases, screening for random mutations was carried out to search for decreased activity against cefotaxime, with the CTX-M-1 gene as a model. Thirteen single mutants with a considerable reduction in cefotaxime MICs were selected for biochemical and stability studies. The 13 mutated genes of the CTX-M-1 β-lactamase were expressed, and the proteins were purified for kinetic studies against cephalothin and cefotaxime (as the main antibiotics). Some of the positions, such as Val103Asp, Asn104Asp, Asn106Lys, and Pro107Ser, are located in the (103)VNYN(106) loop, which had been described as important in cefotaxime hydrolysis, although this has not been experimentally confirmed. There are four mutations located close to catalytic residues-Thr71Ile, Met135Ile, Arg164His, and Asn244Asp-that may affect the positioning of these residues. We show here that some distant mutations, such as Ala219Val, are critical for cefotaxime hydrolysis and highlight the role of this loop at the top of the active site. Other distant substitutions, such as Val80Ala, Arg191, Ala247Ser, and Val260Leu, are in hydrophobic cores and may affect the dynamics and flexibility of the enzyme. We describe here, in conclusion, new residues involved in cefotaxime hydrolysis in CTX-M β-lactamases, five of which are in positions distant from the catalytic center.

  9. Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets.

    Science.gov (United States)

    Fuchs, Ann-Kathrin; Syrovets, Tatiana; Haas, Karina A; Loos, Cornelia; Musyanovych, Anna; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

    2016-04-01

    Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-α and IL-1β, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-β1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization.

  10. M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation.

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    Nissen, Christoph; Power, Ann E; Nofzinger, Eric A; Feige, Bernd; Voderholzer, Ulrich; Kloepfer, Corinna; Waldheim, Bernhard; Radosa, Marc-Philipp; Berger, Mathias; Riemann, Dieter

    2006-11-01

    Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.

  11. High-throughput genotyping of copy number variation in glutathione S-transferases M1 and T1 using real-time PCR in 20,687 individuals

    DEFF Research Database (Denmark)

    Norskov, M.S.; Frikke-Schmidt, R.; Loft, S.;

    2009-01-01

    OBJECTIVES: Characteristic for the genes encoding glutathione S-transferase (GST) M1 and GSTT1 is a null allele, suggested to increase susceptibility to chronic diseases. We report an optimized method for the determination of copy number variation (CNV) in GST genes. DESIGN AND METHODS: Real...... to 100 ng. In a general population sample of 20,687 individuals the genotype frequencies were concordant with other methods used as standards. Throughput was 4600 genotypes per day at a reagent price of 0.5 euros per sample. CONCLUSIONS: This high-throughput, low cost method accurately determines CNV...

  12. Solvent affects the conformation of virginiamycin M1 (pristinamycin IIA, streptogramin A).

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    Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2004-10-21

    The streptogramins are antibiotics which act by binding two different components at separate nearby sites on the bacterial 50S ribosome, inhibiting protein synthesis. The first component, a macrolactone, is common to many of the streptogramin antibiotics and, thus, is referred to by many names including virginiamycin M1(VM1), pristinamycin IIA, ostreogrycin A and streptogramin A. X-Ray crystallographic studies of VM1 bound to ribosomes and to a deactivating enzyme show a different conformation to that of VM1 in chloroform solution. We now report the results of high resolution 2D NMR experiments that show that the conformation of VM1 in dimethyl sulfoxide and methanol differs from both that in chloroform solution and in the bound form. The 3D structure and the 1H NMR and 13C NMR chemical shifts of VM1 in dimethyl sulfoxide and methanol are described.

  13. Glutathione S-transferase M1 (GSTM1) genotype but not GSTT1 or MC1R genotype influences erythemal sensitivity to narrow band (TL-01) UVB phototherapy.

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    Smith, Gillian; Weidlich, Simone; Dawe, Robert S; Ibbotson, Sally H

    2011-04-01

    Although a majority of psoriasis patients respond to treatment with narrow band ultraviolet B radiation (TL-01) phototherapy, it is currently not possible to predict erythemal sensitivity, or to identify treatment responders. A variety of antioxidant enzymes, including the polymorphic glutathione S-transferase GSTM1 and GSTT1 genes, protect the cell from UVR-induced oxidative challenge. GSTM1 and GSTT1 are deleted in approximately 50 and 20% of the Caucasian population, respectively, and GST null genotype has been associated with increased sunburn sensitivity and reduced minimal erythemal dose (MED) after broadband UVR exposure in healthy volunteers and with susceptibility to skin cancer. Another polymorphic determinant of UVR sensitivity is the melanocortin 1 receptor (MC1R), which protects cells from UVR-induced apoptosis and photodamage. Our aim was therefore to investigate whether GST or MC1R genotype influenced erythemal sensitivity to narrow band (TL-01) ultraviolet B radiation phototherapy in patients with psoriasis. We used TaqMan quantitative gene copy and allelic discrimination assays to determine GST and MC1R genotypes, and looked for possible associations between genotype and threshold erythemal sensitivity (MED) and treatment outcomes in patients with psoriasis (n=256). We showed that GSTM1 genotype, but not GSTT1 or MC1R genotype influences erythemal sensitivity to TL-01 phototherapy, with a significantly lower MED observed in GSTM1 null individuals [χ(2 d.f.)=8.862, P=0.012]. None of the genotypes studied were associated with TL-01 treatment outcomes or relapse rates. GSTM1 genotype may have clinical utilityin the prediction of photosensitivity and/or in identifying patients at increased risk of treatment-related side effects.

  14. Association between glutathione S-transferase T1, M1, and P1 genotypes and the risk of colorectal cancer.

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    Cong, Ning; Liu, Lisheng; Xie, Ying; Shao, Wenbo; Song, Jinlong

    2014-11-01

    Glutathione S-transferases (GSTs) are enzymes which play an important role in the neutralization of toxic compounds and eradication of electrophilic carcinogens. Genetic polymorphisms within the genes encoding for GSTs may therefore cause variations in their enzyme activity, which may in turn influence the interindividual susceptibility to cancers. In this study, we aimed to investigate the association between genetic polymorphisms of GSTT1, GSTM1, and GSTP1 and the risk of colorectal cancer (CRC) in 264 cases and 317 controls in a Chinese population. Genotyping was performed by using multiplex PCR (for GSTT1 and GSTM1) and PCR-RFLP (for GSTP1) methods. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Our results showed that individuals with GSTT1 and GSTM1 null genotypes exhibited a higher risk of CRC (GSTT1, OR,1.66; 95% CI, 1.20-2.31, P=0.003; GSTM1, OR,1.57; 95% CI,1.13-2.18, P=0.007), while no association was observed for GSTP1 (P heterozygous=0.790 or P variant=0.261). Furthermore, individuals who simultaneously carried the null genotypes for both GSTT1 and GSTM1 showed a stronger risk association (OR, 1.95; 95% CI, 1.33-2.85; P<0.001). In conclusion, the GSTT1 and GSTM1 polymorphisms, but not GSTP1, may modulate the CRC risk among Chinese.

  15. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration

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    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter

    2017-01-01

    Introduction. Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P1–5) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods. Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results. All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P1. In contrast, M1-polarized macrophages significantly downregulated S1P4. The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion. The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

  16. Frequency of glutathione-S-transferase null-M1 and null-T1 genotypes among the Turabah population in Saudi Arabia.

    Science.gov (United States)

    Mansour, A A; Saleh, O M; Askar, T; Salim, A M; Mergani, A

    2015-12-14

    Glutathione-S-transferases (GST) are key phase II detoxifying enzymes that play critical roles in protection against products of oxidative stress and against electrophiles. Glutathione S-transferase mu (GST-M1) and theta (GST-T1) are isoforms of glutathione transferase enzymes that participate in the metabolism of a wide range of chemicals. Deletion variants that are associated with a lack of enzyme function exist at both these loci. The frequencies of homozygous GSTM1 and GSTT1 deletion carriers are very high in most of the populations studied to date. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 genotypes among the Turabah population in Saudi Arabia in comparison with the data published for some other Arabic populations. The subjects consisted of 164 unrelated healthy individuals from the Turabah population. GST genotyping was performed by multiplex polymerase chain reaction-based methods. The GSTM1 deletion homozygosity was 56.1% and GSTT1 deletion homozygosity was 20.7%, while the GSTM1 and GSTT1 double-deletion homozygosity was 11.0%. Comparison with published data from Bahraini, Lebanese, and Tunisian populations demonstrated no significant difference for GSTM1 between these populations. The GSTT1 null-allele frequency was significantly lower than those for the Lebanese and Tunisian populations (P = 0.001) but similar to that for the Bahraini population (P = 0.099). Characterization of GST genetic polymorphisms in the Saudi population may aid in genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and the pharmacogenetics of chemotherapy.

  17. High-throughput genotyping of copy number variation in glutathione S-transferases M1 and T1 using real-time PCR in 20,687 individuals

    DEFF Research Database (Denmark)

    Norskov, M.S.; Frikke-Schmidt, R.; Loft, S.;

    2009-01-01

    OBJECTIVES: Characteristic for the genes encoding glutathione S-transferase (GST) M1 and GSTT1 is a null allele, suggested to increase susceptibility to chronic diseases. We report an optimized method for the determination of copy number variation (CNV) in GST genes. DESIGN AND METHODS: Real-time...

  18. The effect of cigarette smoke and arsenic exposure on urothelial carcinoma risk is modified by glutathione S-transferase M1 gene null genotype

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    Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Huang, Chao-Yuan; Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Shiue, Horng-Sheng [Department of Chinese Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)

    2013-01-15

    Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain risk factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.

  19. Females with paired occurrence of cancers in the UADT and genital region have a higher frequency of either Glutathione S-transferase M1/T1 null genotype

    Directory of Open Access Journals (Sweden)

    Jhavar Sameer G

    2005-03-01

    Full Text Available Abstract Upper Aero digestive Tract (UADT is the commonest site for the development of second cancer in females after primary cervical cancer. Glutathione S-transferase (GSTM1 and / or T1 null genotype modulates the risk of developing UADT cancer (primary as well as second cancer. The aim of this study was to evaluate the difference in GST null genotype frequencies in females with paired cancers in the UADT and genital region as compared to females with paired cancers in the UADT and non-genital region. Forty-nine females with a cancer in the UADT and another cancer (at all sites-genital and non-genital were identified from a database of patients with multiple primary neoplasms and were analyzed for the GSTM1 and T1 genotype in addition to known factors such as age, tobacco habits, alcohol habits and family history of cancer. Frequencies of GSTM1 null, GSTT1 null, and either GSTM1/T1 null were higher in females with paired occurrence of cancer in the UADT and genital site (54%, 33% and 75% respectively in comparison to females with paired occurrence of cancer in the UADT and non-genital sites (22%, 6% and 24% respectively. The significantly higher inherited frequency of either GSTM1/T1 null genotype in females with a paired occurrence of cancers in UADT and genital region (p = 0.01, suggests that these females are more susceptible to damage by carcinogens as compared to females who have UADT cancers in association with cancers at non-genital sites.

  20. Cropping history affects nodulation and symbiotic efficiency of distinct hairy vetch genotypes with resident soil rhizobia

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    Presence of compatible rhizobia strains is essential for nodulation and BNF of hairy vetch (Vicia villosa, HV). We evaluated how past HV cultivation affects nodulation and nitrogen fixation across host genotypes. Five groups of HV genotypes were inoculated with soil dilutions from six paired fields,...

  1. Alternation of cowpea genotypes affects the biology of Callosobruchus maculatus (fabr. (Coleoptera: Bruchidae

    Directory of Open Access Journals (Sweden)

    Lima Marcileyne Pessôa Leite de

    2004-01-01

    Full Text Available Callosobruchus maculatus (Fabr. is an important pest in stored cowpea, Vigna unguiculata (L. Walp., with ample distribution in tropical and subtropical regions. The effect of alternation of cowpea genotypes, susceptible (S and resistant (R, on the biology of (C. maculatus was studied after four generations. A no-choice test was carried out in a completely randomized design, factorial scheme, with five treatments, four host combinations (RR, RS, SR and SS and five replications. Each replication consisted of 30 grains of each genotype infested by two insect couples. The number of eggs per female was not different within or between combinations, evidencing that the genotypes and their alternation did not affect C. maculatus fecundity. Egg viability, however, varied between genotypes and between combinations. In combination RR, the longest duration of the immature stage was verified for genotype IT89KD-245; in addition, all genotypes presented the smallest survival for the same stage, resulting in a higher mortality of the pest. The resistance index categorized combination RR as moderately resistant for genotypes IT89KD-245, BR14-Mulato and BR17-Gurguéia, and as susceptible (S only for IT89KD-260, demonstrating that these combinations were not very adequate for the development of C. maculatus, a fact that was confirmed by the better performance of the pest on the genotype from combination SS, and because of a reduction in its performance when it returned to resistant genotypes.

  2. Factors affecting genotyping success in giant panda fecal samples.

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    Zhu, Ying; Liu, Hong-Yi; Yang, Hai-Qiong; Li, Yu-Dong; Zhang, He-Min

    2017-01-01

    Fecal samples play an important role in giant panda conservation studies. Optimal preservation conditions and choice of microsatellites for giant panda fecal samples have not been established. In this study, we evaluated the effect of four factors (namely, storage type (ethanol (EtOH), EtOH -20 °C, 2-step storage medium, DMSO/EDTA/Tris/salt buffer (DETs) and frozen at -20 °C), storage time (one, three and six months), fragment length, and repeat motif of microsatellite loci) on the success rate of microsatellite amplification, allelic dropout (ADO) and false allele (FA) rates from giant panda fecal samples. Amplification success and ADO rates differed between the storage types. Freezing was inferior to the other four storage methods based on the lowest average amplification success and the highest ADO rates (P < 0.05). The highest microsatellite amplification success was obtained from either EtOH or the 2-step storage medium at three storage time points. Storage time had a negative effect on the average amplification of microsatellites and samples stored in EtOH and the 2-step storage medium were more stable than the other three storage types. We only detected the effect of repeat motif on ADO and FA rates. The lower ADO and FA rates were obtained from tri- and tetra-nucleotide loci. We suggest that freezing should not be used for giant panda fecal preservation in microsatellite studies, and EtOH and the 2-step storage medium should be chosen on priority for long-term storage. We recommend candidate microsatellite loci with longer repeat motif to ensure greater genotyping success for giant panda fecal studies.

  3. Factors affecting genotyping success in giant panda fecal samples

    Directory of Open Access Journals (Sweden)

    Ying Zhu

    2017-05-01

    Full Text Available Fecal samples play an important role in giant panda conservation studies. Optimal preservation conditions and choice of microsatellites for giant panda fecal samples have not been established. In this study, we evaluated the effect of four factors (namely, storage type (ethanol (EtOH, EtOH −20 °C, 2-step storage medium, DMSO/EDTA/Tris/salt buffer (DETs and frozen at −20 °C, storage time (one, three and six months, fragment length, and repeat motif of microsatellite loci on the success rate of microsatellite amplification, allelic dropout (ADO and false allele (FA rates from giant panda fecal samples. Amplification success and ADO rates differed between the storage types. Freezing was inferior to the other four storage methods based on the lowest average amplification success and the highest ADO rates (P < 0.05. The highest microsatellite amplification success was obtained from either EtOH or the 2-step storage medium at three storage time points. Storage time had a negative effect on the average amplification of microsatellites and samples stored in EtOH and the 2-step storage medium were more stable than the other three storage types. We only detected the effect of repeat motif on ADO and FA rates. The lower ADO and FA rates were obtained from tri- and tetra-nucleotide loci. We suggest that freezing should not be used for giant panda fecal preservation in microsatellite studies, and EtOH and the 2-step storage medium should be chosen on priority for long-term storage. We recommend candidate microsatellite loci with longer repeat motif to ensure greater genotyping success for giant panda fecal studies.

  4. Influence of COMT genotype and affective distractors on the processing of self-generated thought.

    Science.gov (United States)

    Kilford, Emma J; Dumontheil, Iroise; Wood, Nicholas W; Blakemore, Sarah-Jayne

    2015-06-01

    The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val(158)Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, COMT genotype and sex on task accuracy: male, but not female, participants showed a sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function. © The Author (2014). Published by Oxford University Press.

  5. Interaction between host genotype and environmental conditions affects bacterial density in Wolbachia symbiosis

    OpenAIRE

    Mouton, Laurence; Henri, Hélène; Charif, Delphine; Boulétreau, Michel; Vavre, Fabrice

    2007-01-01

    Regulation of microbial population density is a necessity in stable symbiotic interactions. In Wolbachia symbiosis, both bacterial and host genotypes are involved in density regulation, but environmental factors may also affect bacterial population density. Here, we studied the interaction between three strains of Wolbachia in two divergent homozygous lines of the wasp Leptopilina heterotoma at two different temperatures. Wolbachia density varied between the two host genotypes at only one tem...

  6. Maize nutrient uptake affected by genotype and fertilization

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    Đalović Ivica

    2015-01-01

    Full Text Available The content of nutrients in maize are commonly related with fertilization and soil quality and rarely explained with the individual hybrid properties. Therefore, the aim of this study is to access a long term fertilization system on ear leaf of Mg, Fe, Mn and Cu content in six maize hybrids(NS 3014, NS 4015, NS 5043, NS 6010, NS 6030 and NS 7020. Samples were collected from a long-term experiment at the Rimski Šančevi experimental field of the Institute of Field and Vegetable Crops in Novi Sad. The study included maize monoculture and 2-year rotations with the application of NPK and manure. Results showed that ear Mg content was influenced with the treatments, hybrid and their interaction and ranged from 1.77-2.69 g kg-1. Iron variability was significantly affected with the treatments and interaction (hybrid x treatments in range from 103.2 to151.9g kg-1. The ear manganese content (41.1-63.6g kg-1 derived from treatments and hybrid effect and Cu (12.3-23.6 g kg-1 was significantly influenced with treatments. Across all treatments, in average, NS6030 had higher values of nutrient and NS3014 was lower in ear nutrient content. This indicates that vegetation length could favor nutrient accumulation. Obtained results suggested that even on fairly productive soil such as Chernozem hybrid selection and the balanced fertilization is crucial for managing the maize nutrient content. [Projekat Ministarsva nauke Republike Srbije, br. TR031073

  7. Tree species, tree genotypes and tree genotypic diversity levels affect microbe-mediated soil ecosystem functions in a subtropical forest

    OpenAIRE

    Purahong, Witoon; Durka, Walter; Fischer, Markus; Dommert, Sven; Schöps, Ricardo; Buscot, François; Wubet, Tesfaye

    2016-01-01

    Tree species identity and tree genotypes contribute to the shaping of soil microbial communities. However, knowledge about how these two factors influence soil ecosystem functions is still lacking. Furthermore, in forest ecosystems tree genotypes co-occur and interact with each other, thus the effects of tree genotypic diversity on soil ecosystem functions merit attention. Here we investigated the effects of tree species, tree genotypes and genotypic diversity levels, alongside soil physicoch...

  8. Tree species, tree genotypes and tree genotypic diversity levels affect microbe-mediated soil ecosystem functions in a subtropical forest

    Science.gov (United States)

    Purahong, Witoon; Durka, Walter; Fischer, Markus; Dommert, Sven; Schöps, Ricardo; Buscot, François; Wubet, Tesfaye

    2016-11-01

    Tree species identity and tree genotypes contribute to the shaping of soil microbial communities. However, knowledge about how these two factors influence soil ecosystem functions is still lacking. Furthermore, in forest ecosystems tree genotypes co-occur and interact with each other, thus the effects of tree genotypic diversity on soil ecosystem functions merit attention. Here we investigated the effects of tree species, tree genotypes and genotypic diversity levels, alongside soil physicochemical properties, on the overall and specific soil enzyme activity patterns. Our results indicate that tree species identity, tree genotypes and genotypic diversity level have significant influences on overall and specific soil enzyme activity patterns. These three factors influence soil enzyme patterns partly through effects on soil physicochemical properties and substrate quality. Variance partitioning showed that tree species identity, genotypic diversity level, pH and water content all together explained ~30% variations in the overall patterns of soil enzymes. However, we also found that the responses of soil ecosystem functions to tree genotypes and genotypic diversity are complex, being dependent on tree species identity and controlled by multiple factors. Our study highlights the important of inter- and intra-specific variations in tree species in shaping soil ecosystem functions in a subtropical forest.

  9. Tree species, tree genotypes and tree genotypic diversity levels affect microbe-mediated soil ecosystem functions in a subtropical forest

    Science.gov (United States)

    Purahong, Witoon; Durka, Walter; Fischer, Markus; Dommert, Sven; Schöps, Ricardo; Buscot, François; Wubet, Tesfaye

    2016-01-01

    Tree species identity and tree genotypes contribute to the shaping of soil microbial communities. However, knowledge about how these two factors influence soil ecosystem functions is still lacking. Furthermore, in forest ecosystems tree genotypes co-occur and interact with each other, thus the effects of tree genotypic diversity on soil ecosystem functions merit attention. Here we investigated the effects of tree species, tree genotypes and genotypic diversity levels, alongside soil physicochemical properties, on the overall and specific soil enzyme activity patterns. Our results indicate that tree species identity, tree genotypes and genotypic diversity level have significant influences on overall and specific soil enzyme activity patterns. These three factors influence soil enzyme patterns partly through effects on soil physicochemical properties and substrate quality. Variance partitioning showed that tree species identity, genotypic diversity level, pH and water content all together explained ~30% variations in the overall patterns of soil enzymes. However, we also found that the responses of soil ecosystem functions to tree genotypes and genotypic diversity are complex, being dependent on tree species identity and controlled by multiple factors. Our study highlights the important of inter- and intra-specific variations in tree species in shaping soil ecosystem functions in a subtropical forest. PMID:27857198

  10. Estrogen receptor-alpha genotype affects exercise-related reduction of arterial stiffness.

    Science.gov (United States)

    Hayashi, Koichiro; Maeda, Seiji; Iemitsu, Motoyuki; Otsuki, Takeshi; Sugawara, Jun; Tanabe, Takumi; Miyauchi, Takashi; Kuno, Shinya; Ajisaka, Ryuichi; Matsuda, Mitsuo

    2008-02-01

    Arterial stiffness, an independent risk factor for cardiovascular disease, increases with advancing age. Arterial stiffness is improved by regular exercise, but individual responses to exercise training are variable. Given that estrogen and estrogen receptor-alpha (ER-alpha) can induce vasodilation and can exert an antiatherosclerotic effect in vessels, we hypothesized that gene polymorphisms of ER-alpha might influence the ability of regular exercise to improve arterial stiffness in postmenopausal women. One hundred ninety-five healthy postmenopausal women (62 +/- 6 yr, mean +/- SD) participated in our cross-sectional study. We determined the genotype of single-nucleotide polymorphisms (SNP) at -401T/C of intron 1 of the ER-alpha gene. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV), and daily physical activity was estimated by a uniaxial accelerometer. Subjects were divided into active and inactive groups according to the median value (200 kcal.d(-1)) of energy expenditure. baPWV in individuals with the TT variant of -401T/C genotype were significantly higher than for individuals with the TC+CC genotype. No significant differences in mean baPWV values were found between the active group and the inactive group (P = 0.09). A significant reduction of baPWV secondary to increased daily physical activity was observed in individuals with the TC+CC genotype but not in individuals with the TT genotype (TT/active: 1470 +/- 36 cm.s(-1); TT/inactive: 1457 +/- 34 cm.s(-1); TC+CC/active: 1359 +/- 21 cm.s(-1); TC+CC/inactive: 1433 +/- 24 cm.s(-1)). These results suggest that ER-alpha polymorphism affects the regular exercise-related reduction in arterial stiffness in healthy postmenopausal women.

  11. Cold sore susceptibility gene-1 genotypes affect the expression of herpes labialis in unrelated human subjects.

    Science.gov (United States)

    Kriesel, John D; Bhatia, Amiteshwar; Thomas, Alun

    2014-01-01

    Our group has recently described a gene on human chromosome 21, the Cold Sore Susceptibility Gene-1 (CSSG-1, also known as C21orf91), which may confer susceptibility to frequent cold sores in humans. We present here a genotype-phenotype analysis of CSSG-1 in a new, unrelated human population. Seven hundred fifty-eight human subjects were enrolled in a case/control Cold Sore Study. CSSG-1 genotyping, herpes simplex virus 1 (HSV1) serotyping, demographic and phenotypic data was available from 622 analyzed subjects. Six major alleles (H1-H6) were tested for associations with each of the self-reported phenotypes. The statistical analysis was adjusted for age, sex and ethnicity. Genotype-phenotype associations were analyzed from 388 HSV1-seropositive subjects. There were significant CSSG-1 haplotype effects on annual cold sore outbreaks (P=0.006), lifetime cold sores (P=0.012) and perceived cold sore severity (P=0.012). There were relatively consistent trends toward protection from frequent and severe cold sores among those with the H3 or H5/6 haplotypes, whereas those with H1, H2, and H4 haplotypes tended to have more frequent and more severe episodes. Different alleles of the newly described gene CSSG-1 affect the expression of cold sore phenotypes in this new, unrelated human population, confirming the findings of the previous family-based study.

  12. Plant genotype and induced defenses affect the productivity of an insect-killing obligate viral pathogen.

    Science.gov (United States)

    Shikano, Ikkei; McCarthy, Elizabeth M; Elderd, Bret D; Hoover, Kelli

    2017-09-01

    Plant-mediated variations in the outcomes of host-pathogen interactions can strongly affect epizootics and the population dynamics of numerous species, including devastating agricultural pests such as the fall armyworm. Most studies of plant-mediated effects on insect pathogens focus on host mortality, but few have measured pathogen yield, which can affect whether or not an epizootic outbreak occurs. Insects challenged with baculoviruses on different plant species and parts can vary in levels of mortality and yield of infectious stages (occlusion bodies; OBs). We previously demonstrated that soybean genotypes and induced anti-herbivore defenses influence baculovirus infectivity. Here, we used a soybean genotype that strongly reduced baculovirus infectivity when virus was ingested on induced plants (Braxton) and another that did not reduce infectivity (Gasoy), to determine how soybean genotype and induced defenses influence OB yield and speed of kill. These are key fitness measures because baculoviruses are obligate-killing pathogens. We challenged fall armyworm, Spodoptera frugiperda, with the baculovirus S. frugiperda multi-nucleocapsid nucleopolyhedrovirus (SfMNPV) during short or long-term exposure to plant treatments (i.e., induced or non-induced genotypes). Caterpillars were either fed plant treatments only during virus ingestion (short-term exposure to foliage) or from the point of virus ingestion until death (long-term exposure). We found trade-offs of increasing OB yield with slower speed of kill and decreasing virus dose. OB yield increased more with longer time to death and decreased more with increasing virus dose after short-term feeding on Braxton compared with Gasoy. OB yield increased significantly more with time to death in larvae that fed until death on non-induced foliage than induced foliage. Moreover, fewer OBs per unit of host tissue were produced when larvae were fed induced foliage than non-induced foliage. These findings highlight the

  13. Maternal serotonin transporter genotype affects risk for ASD with exposure to prenatal stress.

    Science.gov (United States)

    Hecht, Patrick M; Hudson, Melissa; Connors, Susan L; Tilley, Michael R; Liu, Xudong; Beversdorf, David Q

    2016-11-01

    Stress exposure during gestation is implicated in several neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous research showed that prenatal stress increases risk for ASD with peak exposure during the end of the second and the beginning of the third trimester. However, exposures to prenatal stress do not always result in ASD, suggesting that other factors may interact with environmental stressors to increase ASD risk. The present study examined a maternal genetic variation in the promoter region of the serotonin transporter gene (5-HTTLPR) affecting stress tolerance and its interaction with the effect of environmental stressors on risk for ASD. Two independent cohorts of mothers of ASD children recruited by the University of Missouri and Queen's University were surveyed regarding the prenatal environment and genotyping on 5-HTTLPR was performed to explore this relationship. In both samples, mothers of children with ASD carrying the stress susceptible short allele variant of 5-HTTLPR experienced a greater number of stressors and greater stress severity when compared to mothers carrying the long allele variant. The temporal peak of stressors during gestation in these mothers was consistent with previous findings. Additionally, increased exposure to prenatal stress was not reported in the pregnancies of typically developing siblings from the same mothers, regardless of maternal genotype, suggesting against the possibility that the short allele might increase the recall of stress during pregnancy. The present study provides further evidence of a specific maternal polymorphism that may affect the risk for ASD with exposure to prenatal stress. Autism Res 2016, 9: 1151-1160. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  14. Genotypic and phenotypic diversity does not affect productivity and drought response in competitive stands of Trifolium repens

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    Heidrun eHuber

    2016-03-01

    Full Text Available Clonal plants can form dense canopies in which plants of different genetic origin are competing for the uptake of essential resources. The competitive relationships among these clones are likely to be affected by extreme environmental conditions, such as prolonged drought spells, which are predicted to occur more frequently due to global climate change. This, in turn, may alter characteristics of the ecological system and its associated functioning.We hypothesized that the relative success of individual clones will depend on the size of the ramets as ramets with larger leaves and longer petioles (large ramets were predicted to have a competitive advantage in terms of increased light interception over smaller-sized ramets. Under drier conditions the relative performances of genotypes were expected to change leading to a change in genotype ranking. We also hypothesized that increased genotypic and phenotypic diversity will increase stand performance and resistance to drought. These hypotheses and the mechanisms responsible for shifts in competitive relationships were investigated by subjecting genotypes of the important pasture legume Trifolium repens to competition with either genetically identical clones, genetically different but similarly sized clones, or genetically as well as morphologically different clones under well-watered and dry conditions.Competitive relationships were affected by ramet size with large genotypes outperforming small genotypes in diverse stands in terms of biomass production. However, large genotypes also produced relatively fewer ramets than small genotypes and could not benefit in terms of clonal reproduction from competing with smaller genotypes, indicating that evolutionary shifts in genotype composition will depend on whether ramet size or ramet number is under selection. In contrast to our hypotheses, diversity did not increase stand performance under different selection regimes and genotype ranking was hardly

  15. Genotyping the High Altitude Mestizo Ecuadorian Population Affected with Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Andrés López-Cortés

    2017-01-01

    Full Text Available Prostate cancer (PC is the second most commonly diagnosed type of cancer in males with 1,114,072 new cases in 2015. The MTHFR enzyme acts in the folate metabolism, which is essential in methylation and synthesis of nucleic acids. MTHFR C677T alters homocysteine levels and folate assimilation associated with DNA damage. Androgens play essential roles in prostate growth. The SRD5A2 enzyme metabolizes testosterone and the V89L polymorphism reduces in vivo SRD5A2 activity. The androgen receptor gene codes for a three-domain protein that contains two polymorphic trinucleotide repeats (CAG, GGC. Therefore, it is essential to know how PC risk is associated with clinical features and polymorphisms in high altitude Ecuadorian mestizo populations. We analyzed 480 healthy and 326 affected men from our three retrospective case-control studies. We found significant association between MTHFR C/T (odds ratio [OR] = 2.2; P=0.009, MTHFR C/T+T/T (OR = 2.22; P=0.009, and PC. The SRD5A2 A49T substitution was associated with higher pTNM stage (OR = 2.88; P=0.039 and elevated Gleason grade (OR = 3.15; P=0.004. Additionally, patients with ≤21 CAG repeats have an increased risk of developing PC (OR = 2.99; P<0.001. In conclusion, genotype polymorphism studies are important to characterize genetic variations in high altitude mestizo populations.

  16. Prevalence of HBV genotypes in South American immigrants affected by HBV-related chronic active hepatitis

    Directory of Open Access Journals (Sweden)

    Emilio Palumbo

    2007-06-01

    Full Text Available This study evaluated the prevalence of HBV infection in a population of South American immigrants in Italy and to determine in patients with detectable serum HBV-DNA the HBVgenotypes. Between April 2005 and April 2006 a total of 130 South American immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV were evaluated. In patients with detectable serum HBV DNA, the HBV genotype was determined by INNOLiPA. Among the 130 subjects tested, 14 (10.7% resulted HBsAg positive. All were men, with a mean age of 22 years (range 19-37 and 12 (85.7 % came from Brazil, while 2 (14.3% came from Ecuador. All patients infected by HBV had elevated alanine-aminotransferase serum levels (mean level was 127 IU/L, range 74-312 and serum HBV DNA detectable by PCR-Real Time (mean level 1,037,652 copies/mL, range 19,876-1,377,648. Genotype distribution was as follow: genotype D, 9 (64.2%, genotype A, 5 (35.8%. All patients infected by genotype D came from Brazil, while among the patients infected by genotype A, three came from Brazil and two from Ecuador. Our study evidences a moderate prevalence of HBV-infection in South American immigrants with the identification of two genotypes, D and A. These genotypes are not the most prevalent in the South America and this is probably the expression of a possible geographical redistribution of HBV genotypes.

  17. Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome

    Science.gov (United States)

    Mills, Philippa B.; Camuzeaux, Stephane S.M.; Footitt, Emma J.; Mills, Kevin A.; Gissen, Paul; Fisher, Laura; Das, Krishna B.; Varadkar, Sophia M.; Zuberi, Sameer; McWilliam, Robert; Stödberg, Tommy; Plecko, Barbara; Baumgartner, Matthias R.; Maier, Oliver; Calvert, Sophie; Riney, Kate; Wolf, Nicole I.; Livingston, John H.; Bala, Pronab; Morel, Chantal F.; Feillet, François; Raimondi, Francesco; Del Giudice, Ennio; Chong, W. Kling; Pitt, Matthew

    2014-01-01

    The first described patients with pyridox(am)ine 5’-phosphate oxidase deficiency all had neonatal onset seizures that did not respond to treatment with pyridoxine but responded to treatment with pyridoxal 5’-phosphate. Our data suggest, however, that the clinical spectrum of pyridox(am)ine 5’-phosphate oxidase deficiency is much broader than has been reported in the literature. Sequencing of the PNPO gene was undertaken for a cohort of 82 individuals who had shown a reduction in frequency and severity of seizures in response to pyridoxine or pyridoxal 5’-phosphate. Novel sequence changes were studied using a new cell-free expression system and a mass spectrometry-based assay for pyridoxamine phosphate oxidase. Three groups of patients with PNPO mutations that had reduced enzyme activity were identified: (i) patients with neonatal onset seizures responding to pyridoxal 5’-phosphate (n = 6); (ii) a patient with infantile spasms (onset 5 months) responsive to pyridoxal 5’-phosphate (n = 1); and (iii) patients with seizures starting under 3 months of age responding to pyridoxine (n = 8). Data suggest that certain genotypes (R225H/C and D33V) are more likely to result in seizures that to respond to treatment with pyridoxine. Other mutations seem to be associated with infertility, miscarriage and prematurity. However, the situation is clearly complex with the same combination of mutations being seen in patients who responded and did not respond to pyridoxine. It is possible that pyridoxine responsiveness in PNPO deficiency is affected by prematurity and age at the time of the therapeutic trial. Other additional factors that are likely to influence treatment response and outcome include riboflavin status and how well the foetus has been supplied with vitamin B6 by the mother. For some patients there was a worsening of symptoms on changing from pyridoxine to pyridoxal 5’-phosphate. Many of the mutations in PNPO affected residues involved in binding flavin

  18. Yield and nutritional quality of greenhouse lettuce (Lactuca sativa L. as affected by genotype and production methods

    Directory of Open Access Journals (Sweden)

    Govedarica-Lučić Aleksandra

    2014-01-01

    Full Text Available Greenhouse experiments were conducted in winter growing seasons in order to evaluate the effects of genotype and production methods on yield and nutritional quality of lettuce (Lactuca sativa L.. A three-year (2009-2011 study was conducted by randomized block system in a greenhouse without additional heating. The trial included three genotypes of lettuce (Archimedes RZ, Santoro RZ, Kibou RZ. Each row with these genotypes was exposed to the following variants of covering: control-planting on bare soil, mulching before sowing with PE-black foil, agro textile-covering plants after planting with agro textile (17 g, a combination of mulching + agro textile. Throughout of all the three years of the trial, it was continuously evidenced that the genotype “Santoro RZ” had the biggest heads and the highest yield (15.33 kg 10 m-2, which leads to conclusion that the yield of lettuce is a genotype characteristics. Moreover, the nutritional value (ascorbic acid concentration has shown that, depending on the method of production, in average, the combination of mulching + agro textile (26.77 mg 100 g-1 had the highest content while the control variant had significantly lower vitamin C content (21.10 mg 100 g-1. The three-year researches have shown that the production method and genotype significantly affect the nitrate content. An average nitrate content was 2196.33 mg kg-1 on the control variant, and 2526.24 mg kg-1 on agro textile. Leafy lettuce of genotyp „Kibou RZ“ had lower nitrate content (2176.85 mg kg-1 compared to „Archimedes RZ“ (2843.05 mg kg-1 and „Santoro RZ“ (2221.37 mg kg-1. However nitrate concentration in all treatments remained within the European Union’s permissible levels.

  19. COMT Val108/158 Met Genotype Affects Neural but not Cognitive Processing in Healthy Individuals

    Science.gov (United States)

    Need, Anna C.; LaBar, Kevin S.; Waters-Metenier, Sheena; Cirulli, Elizabeth T.; Kragel, James; Goldstein, David B.; Cabeza, Roberto

    2010-01-01

    The relationship between cognition and a functional polymorphism in the catechol-O-methlytransferase (COMT) gene, val108/158met, is one of debate in the literature. Furthermore, based on the dopaminergic differences associated with the COMT val108/158met genotype, neural differences during cognition may be present, regardless of genotypic differences in cognitive performance. To investigate these issues the current study aimed to 1) examine the effects of COMT genotype using a large sample of healthy individuals (n = 496–1218) and multiple cognitive measures, and using a subset of the sample (n = 22), 2) examine whether COMT genotype effects medial temporal lobe (MTL) and frontal activity during successful relational memory processing, and 3) investigate group differences in functional connectivity associated with successful relational memory processing. Results revealed no significant group difference in cognitive performance between COMT genotypes in any of the 19 cognitive measures. However, in the subset sample, COMT val homozygotes exhibited significantly decreased MTL and increased prefrontal activity during both successful relational encoding and retrieval, and reduced connectivity between these regions compared with met homozygotes. Taken together, the results suggest that although the COMT val108/158met genotype has no effect on cognitive behavioral measures in healthy individuals, it is associated with differences in neural process underlying cognitive output. PMID:19641018

  20. Catechol-O-methyltransferase (COMT Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Stephan Heinzel

    2014-01-01

    Full Text Available Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years and 25 older (aged 60–75 years healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P<.001, which was larger in younger as compared to older adults (P<.001. Age-related differences were qualified by an interaction with COMT genotype (P<.001, and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.

  1. Catechol-O-methyltransferase (COMT) Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Science.gov (United States)

    Riemer, Thomas G.; Schulte, Stefanie; Onken, Johanna; Heinz, Andreas; Rapp, Michael A.

    2014-01-01

    Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT) amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years) and 25 older (aged 60–75 years) healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P < .001), which was larger in younger as compared to older adults (P < .001). Age-related differences were qualified by an interaction with COMT genotype (P < .001), and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism. PMID:24772423

  2. Sugarcane genotype variation in leaf photosynthesis properties and yield as affected by mill mud application

    Science.gov (United States)

    Variability in yield among sugarcane (a complex hybrid of Saccharum spp.) genotypes grown with and without mill mud application on sand soils in Florida has been documented, but little is known about what causes yield differences and if there are any relationships between yield components and physio...

  3. A comparison of bioactive compounds of strawberry fruit from Europe affected by genotype and latitude

    DEFF Research Database (Denmark)

    Josuttis, M.; Carlen, C.; Nestby, R.

    2012-01-01

    The effect of four different growing locations from Stjørdal, Norway (63°36'N) to Conthey, Switzerland (46°12'N) on the composition of bioactives in strawberry (Fragaria × ananassa Duch.) of three genotypes (cvs Clery, Elsanta and Korona) was evaluated. Principal component analysis (PCA) was used...

  4. Genotypic variation in tetraploid wheat affecting homoeologous pairing in hybrids with Aegilops peregrina.

    Science.gov (United States)

    Ozkan, H; Feldman, M

    2001-12-01

    The Ph1 gene has long been considered the main factor responsible for the diploid-like meiotic behavior of polyploid wheat. This dominant gene, located on the long arm of chromosome 5B (5BL), suppresses pairing of homoeologous chromosomes in polyploid wheat and in their hybrids with related species. Here we report on the discovery of genotypic variation among tetraploid wheats in the control of homoeologous pairing. Compared with the level of homoeologous pairing in hybrids between Aegilops peregrina and the bread wheat cultivar Chinese Spring (CS), significantly higher levels of homoeologous pairing were obtained in hybrids between Ae. peregrina and CS substitution lines in which chromosome 5B of CS was replaced by either 5B of Triticum turgidum ssp. dicoccoides line 09 (TTD09) or 5G of Triticum timopheevii ssp. timopheevii line 01 (TIMO1). Similarly, a higher level of homoeologous pairing was found in the hybrid between Ae. peregrina and a substitution line of CS in which chromosome arm 5BL of line TTD140 substituted for 5BL of CS. It appears that the observed effect on the level of pairing is exerted by chromosome arm 5BL of T turgidum ssp. dicoccoides, most probably by an allele of Ph1. Searching for variation in the control of homoeologous pairing among lines of wild tetraploid wheat, either T turgidum ssp. dicoccoides or T timopheevii ssp. armeniacum, showed that hybrids between Ae. peregrina and lines of these two wild wheats exhibited three different levels of homoeologous pairing: low, low intermediate, and high intermediate. The low-intermediate and high-intermediate genotypes may possess weak alleles of Ph1. The three different T turgidum ssp. dicoccoides pairing genotypes were collected from different geographical regions in Israel, indicating that this trait may have an adaptive value. The availability of allelic variation at the Ph1 locus may facilitate the mapping, tagging, and eventually the isolation of this important gene.

  5. GSTM1 and APE1 genotypes affect arsenic-induced oxidative stress: a repeated measures study

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    Quamruzzaman Quazi

    2007-12-01

    Full Text Available Abstract Background Chronic arsenic exposure is associated with an increased risk of skin, bladder and lung cancers. Generation of oxidative stress may contribute to arsenic carcinogenesis. Methods To investigate the association between arsenic exposure and oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG was evaluated in a cohort of 97 women recruited from an arsenic-endemic region of Bangladesh in 2003. Arsenic exposure was measured in urine, toenails, and drinking water. Drinking water and urine samples were collected on three consecutive days. Susceptibility to oxidative stress was evaluated by genotyping relevant polymorphisms in glutathione-s transferase mu (GSTM1, human 8-oxoguanine glycosylase (hOGG1 and apurinic/apyrimidinic endonuclease (APE1 genes using the Taqman method. Data were analyzed using random effects Tobit regression to account for repeated measures and 8-OHdG values below the detection limit. Results A consistent negative effect for APE1 was observed across water, toenail and urinary arsenic models. APE1 148 glu/glu + asp/glu genotype was associated with a decrease in logged 8-OHdG of 0.40 (95%CI -0.73, -0.07 compared to APE1 148 asp/asp. An association between total urinary arsenic and 8-OHdG was observed among women with the GSTM1 null genotype but not in women with GSTM1 positive. Among women with GSTM1 null, a comparison of the second, third, and fourth quartiles of total urinary arsenic to the first quartile resulted in a 0.84 increase (95% CI 0.27, 1.42, a 0.98 increase (95% CI 033, 1.66 and a 0.85 increase (95% CI 0.27, 1.44 in logged 8-OHdG, respectively. No effects between 8-OHdG and toenail arsenic or drinking water arsenic were observed. Conclusion These results suggest the APE1 variant genotype decreases repair of 8-OHdG and that arsenic exposure is associated with oxidative stress in women who lack a functional GSTM1 detoxification enzyme.

  6. Does Apolipoprotein E genotype affect cardiovascular risk in subjects with acromegaly?

    Science.gov (United States)

    Bozok Cetintas, Vildan; Zengi, Ayhan; Tetik, Asli; Karadeniz, Muammer; Ergonen, Faruk; Kucukaslan, Ali Sahin; Tamsel, Sadik; Kosova, Buket; Sahin, Serap Baydur; Saygılı, Fusun; Eroglu, Zuhal

    2012-06-01

    Acromegaly is a syndrome that results when the pituitary gland produces excess growth hormone after epiphyseal closure at puberty. Usually, subjects with acromegaly exhibit a 2- to 3-fold higher mortality rate from diseases that are associated with cardiovascular complications when compared to the normal population. In this study, we therefore aimed to evaluate whether a well-established cardiovascular risk factor, the Apolipoprotein E (Apo E) genotype, contributes to increased risk of cardiovascular complications in subjects with acromegaly. A total of 102 unrelated acromegaly subjects were prospectively included into this case-control association study and constituted our study group. The study group was comparable by age and gender with 200 unrelated healthy subjects constituting our control group. Genomic DNA was isolated from the peripheral blood leukocytes of all subjects and Apo E genotype (codon 112/158) was assessed by melting temperature analyses after using a real-time PCR protocol. The Apolipoprotein E4 allele was found at a significantly higher frequency in the study group when compared with the control group (P = 0.032). Subjects with the E2 allele, on the other hand, had significantly increased values in body mass index (P = 0.004), waist circumference (P = 0.001), C-reactive protein (CRP) (P acromegaly since it is concurrently present with other cardiovascular risk factors such as the left-side carotid intima media thickness and CRP.

  7. Genotype-based changes in serum uric acid affect blood pressure

    Science.gov (United States)

    Parsa, Afshin; Brown, Eric; Weir, Matthew R.; Fink, Jeffrey C.; Shuldiner, Alan R.; Mitchell, Braxton D.; McArdle, Patrick F.

    2013-01-01

    Elevated serum levels of uric acid consistently correlate with hypertension, but the directionality of the association remains debated. To help define this relationship, we used a controlled setting within a homogeneous Amish community and the Mendelian randomization of a nonsynonymous coding single-nucleotide polymorphism, rs16890979 (Val253Ile), in the SLC2A9 gene. This gene expresses the GLUT9 transporter that also transports uric acid and is associated with lower serum uric acid levels. We studied the unconfounded association between genotype and blood pressure in 516 Amish adults, each placed for 6 days on standardized diets, first with high sodium, followed by low sodium, with an intervening washout period. Blood pressure, measured using 24-h ambulatory monitoring, during both diet periods was used as the primary outcome. All participants were free of diuretic or other antihypertensive medications and the relationships between GLUT9 genotype and both serum uric acid and blood pressure were assessed. Each copy of the GLUT9 minor Ile allele was found to confer a significant 0.44 mg/dl reduction in serum uric acid and was associated with a significant mean decrease in the systolic blood pressure of 2.2 and 1.5 mm Hg on the high- and low-sodium diet, respectively. Thus, a Mendelian randomization analysis using variants in the GLUT9 gene indicates that a decrease in serum uric acid has a causal effect of lowering blood pressure. PMID:22189840

  8. Skeletal muscle strength in older adults. Angiotensin-converting enzyme (ACE genotype affects: an UPDATE

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    ANA PEREIRA

    2011-06-01

    Full Text Available Problem Statement : Previous studies have associated angiotensin-converting enzyme (ACE with variability inthe skeletal muscle baseline strength, though conclusions have been inconsistent across investigations.Approach: The purpose of this study was to review the most important studies that have been exanimate thepossible association between ACE genotype and skeletal muscle baseline strength in elite male and femaleathletes involved in elderly populations. This research is needed because the possibility that the DD genotypemay be associated with a greater proportion of fast twitch fibers could explain the influence of the ACE D alleleupon strength/ power, particularly at high velocities, but this evidence remains equivocal in older people becausemore studies are necessary.Results: Thus, according to scientific evidence, changes in muscle strength with exercise training in olderindividuals may be dependent on ACE I/D genotype. Of note, the results provide a novel insight that thesegenetic variations may interact to determine muscle mass in older women specially. The determination of thispredisposition in this population, highlighting the interest of study, for the prophylactic attitude on the factorsand causes of aging (sarcopenia, osteoporosis, risk of falls, reduction of functional physical go through thisanalysis.Conclusions/Recommendations: In this work, the state of the art related to the influence of the ACE genotypeon skeletal muscle strength was presented and some important relations were reported

  9. Angiotensin-converting enzyme genotype affects skeletal muscle strength in elite athletes.

    Science.gov (United States)

    Costa, Aldo Matos; Silva, António José; Garrido, Nuno; Louro, Hugo; Marinho, Daniel Almeida; Cardoso Marques, Mário; Breitenfeld, Luiza

    2009-01-01

    Previous studies have associated angiotensin-converting enzyme (ACE) D allele with variability in the skeletal muscle baseline strength, though conclusions have been inconsistent across investigations. The purpose of this study was to examine the possible association between ACE genotype and skeletal muscle baseline strength in elite male and female athletes involved in different event expertise. A group of 58 elite athletes, designated as Olympic candidates, were studied: 35 swimmers (19 males and 16 females, 18.8 ± 3.2 years) and 23 triathletes (15 males and 8 females, 18.7 ± 3.0 years). The athletes were classified as: short (≤ 200m) and middle (400m to 1500m) distance athletes, respectively. For each subject the grip strength in both hands was measure using an adjustable mechanical hand dynamometer. The maximum height in both squat jump (SJ) and counter movement jump (CMJ) were also assessed, using a trigonometric carpet (Ergojump Digitime 1000; Digitest, Jyvaskyla, Finland). DNA extraction was obtained with Chelex 100(®) and genotype determination by PCR-RFLP methods. Both males and females showed significantly higher right grip strength in D allele carriers compared to II homozygote's. We found that allelic frequency differs significantly by event distance specialization in both genders (p sprinter D allele carriers showed the superior scores in nearly all strength measurements (p < 0.05), in both genders. Among endurance athletes, the results also demonstrated that female D allele carriers exhibited the higher performance right grip and CMJ scores (p < 0.05). In conclusion, the ACE D allele seems associated with skeletal muscle baseline strength in elite athletes, being easily identified in females. Key pointsDD homozygote's and D allele carriers from both genders shows significantly higher right grip strength.Right grip strength remains significantly higher in the D allele carrier's female endurance group.Female's D allele carriers exhibited the higher

  10. Affect-modulated startle: interactive influence of catechol-O-methyltransferase Val158Met genotype and childhood trauma.

    Science.gov (United States)

    Klauke, Benedikt; Winter, Bernward; Gajewska, Agnes; Zwanzger, Peter; Reif, Andreas; Herrmann, Martin J; Dlugos, Andrea; Warrings, Bodo; Jacob, Christian; Mühlberger, Andreas; Arolt, Volker; Pauli, Paul; Deckert, Jürgen; Domschke, Katharina

    2012-01-01

    The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.

  11. Affect-modulated startle: interactive influence of catechol-O-methyltransferase Val158Met genotype and childhood trauma.

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    Benedikt Klauke

    Full Text Available The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design and childhood maltreatment (CTQ as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.

  12. Factors Affecting Phenotype Variability in a Family with CMT2B: Gender and LRSAM1 Genotype

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    Leema Reddy Peddareddygari

    2016-06-01

    Full Text Available Charcot-Marie-Tooth disease type 2 (CMT2 is an autosomal dominant axonal neuropathy caused by mutations in various genes. The subtype CMT2B results from missense mutations in RAB7A, member RAS oncogene family gene, whereas missense mutations in the Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1 gene cause CMT2P. We describe the genotype/phenotype analysis of a family in which a previously described mutation in the RAB7A gene and a novel mutation in the LRSAM1 gene were identified. In this family, none of the individuals had ulceromutilating features, and there was a marked variability in the age of onset. We discuss the possible etiology of the observed phenotypic variability including the role of gender and possible RAB7A/LRSAM1 gene interactions.

  13. Characterization of high-yield performance as affected by genotype and environment in rice

    Institute of Scientific and Technical Information of China (English)

    Song CHEN; Fang-rong ZENG; Zong-zhi PAO; Guo-ping ZHANG

    2008-01-01

    We characterized yield-relevant characters and their variations over genotypes and environments (locations and years) by examining two rice varieties (9746 and Jinfeng) with high yield potential.9746 and Jinfeng were planted in two locations of Shanghai,China,during 2005 and 2006.The results show that there was a large variation in grain yield between locations and years.The realization of high yield potential for the two types of rice was closely related to the improved sink size,such as more panicles per square meter or grains per panicle.Stem and leaf biomasses were mainly accumulated from tillering stage to heading stage,and showed slow decline during grain filling.Meanwhile,some photosynthetic characters including net photosynthesis rate (Pn),leaf area index (LAI),specific leaf area (SLA),fluorescence parameter (maximum quantum yield of PSII,Fv/Fm),chlorophyll content (expressed as SPAD value),as well as nutrient (N,P,K) uptake were also measured to determine their variations over genotypes and environments and their relationships with grain yield.Although there were significant differences between years or locations for most measurements,SLA at tillering and heading stages,Fv/Fm and LAI at heading stage,stem biomass at heading and maturity stages,and leaf nitrogen concentration at tillering and heading stages remained little changed,indicating their pos-sible applications as selectable characters in breeding programs.It was also found that stem nitrogen accumulation at tillering stage is one of the most important and stable traits for high yield formation.

  14. ANGIOTENSIN-CONVERTING ENZYME GENOTYPE AFFECTS SKELETAL MUSCLE STRENGTH IN ELITE ATHLETES

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    Aldo Matos Costa

    2009-09-01

    Full Text Available Previous studies have associated angiotensin-converting enzyme (ACE D allele with variability in the skeletal muscle baseline strength, though conclusions have been inconsistent across investigations. The purpose of this study was to examine the possible association between ACE genotype and skeletal muscle baseline strength in elite male and female athletes involved in different event expertise. A group of 58 elite athletes, designated as Olympic candidates, were studied: 35 swimmers (19 males and 16 females, 18.8 ± 3.2 years and 23 triathletes (15 males and 8 females, 18.7 ± 3.0 years. The athletes were classified as: short (< 200m and middle (400m to 1500m distance athletes, respectively. For each subject the grip strength in both hands was measure using an adjustable mechanical hand dynamometer. The maximum height in both squat jump (SJ and counter movement jump (CMJ were also assessed, using a trigonometric carpet (Ergojump Digitime 1000; Digitest, Jyvaskyla, Finland. DNA extraction was obtained with Chelex 100® and genotype determination by PCR-RFLP methods. Both males and females showed significantly higher right grip strength in D allele carriers compared to II homozygote's. We found that allelic frequency differs significantly by event distance specialization in both genders (p < 0.05. In fact, sprinter D allele carriers showed the superior scores in nearly all strength measurements (p < 0.05, in both genders. Among endurance athletes, the results also demonstrated that female D allele carriers exhibited the higher performance right grip and CMJ scores (p < 0.05. In conclusion, the ACE D allele seems associated with skeletal muscle baseline strength in elite athletes, being easily identified in females

  15. Variations in Concentration and Distribution of Health-Related Elements Affected by Environmental and Genotypic Differences in Rice Grains

    Institute of Scientific and Technical Information of China (English)

    REN Xue-liang; LIU Qing-long; WU Dian-xing; SHU Qing-yao

    2006-01-01

    A research work was conducted to investigate the variations in concentration and distribution of health-related elements affected by environmental and genotypic differences in rice grains. The grain of Xieqingzao B (indica rice variety) and Xiushui 110 (japonica rice variety) were divided into: hull, bran and milled rice, based on the conventional rice consumption and process. Xieqingzao B was grown at four different locations, and at one location, it was planted in the same field and season as Xiushui 110. In addition, another four indica and four japonica varieties were cultivated in the same field and time to analyze the elements in milled rice. The average concentrations of total P and phytic acid P were the highest in the bran, followed by milled rice and hull; Zn, K, Mg, and As concentrations were the highest in bran, followed by hull and milled rice, while Fe, Ca, and Cu concentrations were the highest in the hull, but similar in bran and milled rice. The result indicated that genotype and environment significantly affected the concentrations of all the tested elements, while the distribution of the above elements in grains was not in the same order as concentration. Moreover, all the elements except 97.7% of Cu and 93.2% of Fe was deposited in the hull on average, were mostly distributed either in the bran (37.3% and 57.7% for K and phytic acid P) or in milled rice (41.7%, 42.6%, 40.3%, 49.8% for Zn, Mg, As, total P, respectively).

  16. GSM(m,1)(m=1,2)模型的数值解%Numeriacl Solution of GSM (m, 1)(m= 1,2)Model

    Institute of Scientific and Technical Information of China (English)

    吴强; 刘炳琪

    2001-01-01

    The prediction accuracy can be improved by using the spline function to correct the residue of GM (m,1)(m=1,2). Numerical Solution of GSM (m,1)(m=1,2)Modle is given.%本文用样条函数对GM(m,1)(m=1,2)模型的残差序列进行插值拟合,得到GSM(m,1)(m=1,2)模型的数值解.

  17. Remobilization of Dry Matter, Nitrogen and Phosphorus in Durum Wheat as Affected by Genotype and Environment

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    Alessandro Masoni

    2007-09-01

    Full Text Available Field studies were carried out to determine dry matter (DM, nitrogen (N and phosphorus (P assimilation until anthesis and DM, N and P remobilization during grain filling in wheat. Twentyfive durum wheat (Triticum durum L. varieties were grown in Tuscany at Grosseto and at Arezzo. At Grosseto 76% of DM was assimilated during pre-anthesis while at Arezzo the amount was 81%. At Grosseto 44% and at Arezzo 35% of N was accumulated until anthesis, while 33% of P was stored until anthesis in both localities. Cultivar differences in DM and N remobilization were positively related to pre-anthesis dry matter and N content at anthesis (r > 0.74. Environmental contraints on carbon, N and P availability in the plant are crucial factors in determining grain yield and N and P content in grain, affecting both accumulation and remobilization. In the low rainfall site of Grosseto, most of the grain yield originated from dry matter accumulation, while in the wetter environment of Arezzo remobilization and accumulation contributed equally to grain yield. Conversely, at Grosseto grain N content relied most on remobilization and at Arezzo remobilization and accumulation contributed equally. Finally, at Grosseto and at Arezzo accumulation of P was the main source of grain P content.

  18. Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson's disease.

    Science.gov (United States)

    Habak, Claudine; Noreau, Anne; Nagano-Saito, Atsuko; Mejía-Constaín, Beatriz; Degroot, Clotilde; Strafella, Antonio P; Chouinard, Sylvain; Lafontaine, Anne-Louise; Rouleau, Guy A; Monchi, Oury

    2014-11-01

    Parkinson's disease is a neurodegenerative condition that affects motor function along with a wide range of cognitive domains, including executive function. The hallmark of the pathology is its significant loss of nigrostriatal dopamine, which is necessary for the cortico-striatal interactions that underlie executive control. Striatal dopamine reuptake is mediated by the SLC6A3 gene (formerly named DAT1) and its polymorphisms, which have been largely overlooked in Parkinson's disease. Thirty patients (ages 53-68 years; 19 males, 11 females) at early stages of Parkinson's disease, were genotyped according to a 9-repeat (9R) or 10-repeat (10R) allele on the SLC6A3/DAT1 gene. They underwent neuropsychological assessment and functional magnetic resonance imaging while performing a set-shifting task (a computerized Wisconsin Card Sorting Task) that relies on fronto-striatal interactions. Patients homozygous on the 10R allele performed significantly better on working memory tasks than 9R-carrier patients. Most importantly, patients carrying a 9R allele exhibited less activation than their 10R homozygous counterparts in the prefrontal cortex, premotor cortex and caudate nucleus, when planning and executing a set-shift. This pattern was exacerbated for conditions that usually recruit the striatum compared to those that do not. This is the first study indicating that the SLC6A3/DAT1 genotype has a significant effect on fronto-striatal activation and performance in Parkinson's disease. This effect is stronger for conditions that engage the striatum. Longitudinal studies are warranted to assess this polymorphism's effect on the clinical evolution of patients with Parkinson's disease, especially with cognitive decline.

  19. COMT and 5-HT1A-receptor genotypes potentially affect executive functions improvement after cognitive remediation in schizophrenia

    Science.gov (United States)

    Bosia, Marta; Bechi, Margherita; Pirovano, Adele; Buonocore, Mariachiara; Lorenzi, Cristina; Cocchi, Federica; Bramanti, Placido; Smeraldi, Enrico; Cavallaro, Roberto

    2014-01-01

    Cognitive remediation therapy (CRT) has been proved to improve cognitive deficits in schizophrenia and to enhance functional outcomes of classical rehabilitation. However, CRT outcomes are heterogeneous and predictors of response are still unknown. Genetic variability, especially in the dopaminergic system, has been hypothesized to affect CRT. We previously reported that rs4680 of the catechol-O-methyltrasferase (COMT) influences improvements in executive functions in patients treated with CRT, but this result was not confirmed by other studies. Such inconsistent findings may depend, other than on clinical variables, also on other genes involved in cognition. Recent studies proved that serotonin 1A receptor (5-HT1A-R) regulates dopamine in the prefrontal cortex (PFC), and clinical works suggested a 5-HT1A-R role in cognition. We then analysed possible effects of COMT rs4680 and 5-HT1A-R rs6295 on CRT outcomes, taking into account also clinical and demographic factors. Eighty-six clinically stabilized schizophrenia patients treated with three months CRT were assessed with the Wisconsin Card Sorting Test, as a measure of executive functions, at enrolment and after CRT treatment, and underwent COMT and 5-HT1A-R genotyping. We found a significant main effect of COMT genotype and an interaction with 5-HT1A-R on executive function improvement after CRT. The results suggest that these two polymorphisms may have an additive effect on individual capacity to recover from cognitive deficit, probably through their role on PFC dopaminergic transmission modulation, known to be critical for modulating cognitive functions. PMID:25750798

  20. Genotype-environment interactions affecting preflowering physiological and morphological traits of Brassica rapa grown in two watering regimes.

    Science.gov (United States)

    El-Soda, Mohamed; Boer, Martin P; Bagheri, Hedayat; Hanhart, Corrie J; Koornneef, Maarten; Aarts, Mark G M

    2014-02-01

    Plant growth and productivity are greatly affected by drought, which is likely to become more threatening with the predicted global temperature increase. Understanding the genetic architecture of complex quantitative traits and their interaction with water availability may lead to improved crop adaptation to a wide range of environments. Here, the genetic basis of 20 physiological and morphological traits is explored by describing plant performance and growth in a Brassica rapa recombinant inbred line (RIL) population grown on a sandy substrate supplemented with nutrient solution, under control and drought conditions. Altogether, 54 quantitative trait loci (QTL) were identified, of which many colocated in 11 QTL clusters. Seventeen QTL showed significant QTL-environment interaction (Q×E), indicating genetic variation for phenotypic plasticity. Of the measured traits, only hypocotyl length did not show significant genotype-environment interaction (G×E) in both environments in all experiments. Correlation analysis showed that, in the control environment, stomatal conductance was positively correlated with total leaf dry weight (DW) and aboveground DW, whereas in the drought environment, stomatal conductance showed a significant negative correlation with total leaf DW and aboveground DW. This correlation was explained by antagonistic fitness effects in the drought environment, controlled by a QTL cluster on chromosome A7. These results demonstrate that Q×E is an important component of the genetic variance and can play a great role in improving drought tolerance in future breeding programmes.

  1. Genotype-dependent molecular evolution of sheep bovine spongiform encephalopathy (BSE) prions in vitro affects their zoonotic potential.

    Science.gov (United States)

    Krejciova, Zuzana; Barria, Marcelo A; Jones, Michael; Ironside, James W; Jeffrey, Martin; González, Lorenzo; Head, Mark W

    2014-09-19

    Prion diseases are rare fatal neurological conditions of humans and animals, one of which (variant Creutzfeldt-Jakob disease) is known to be a zoonotic form of the cattle disease bovine spongiform encephalopathy (BSE). What makes one animal prion disease zoonotic and others not is poorly understood, but it appears to involve compatibility between the prion strain and the host prion protein sequence. Concerns have been raised that the United Kingdom sheep flock may have been exposed to BSE early in the cattle BSE epidemic and that serial BSE transmission in sheep might have resulted in adaptation of the agent, which may have come to phenotypically resemble scrapie while maintaining its pathogenicity for humans. We have modeled this scenario in vitro. Extrapolation from our results suggests that if BSE were to infect sheep in the field it may, with time and in some sheep genotypes, become scrapie-like at the molecular level. However, the results also suggest that if BSE in sheep were to come to resemble scrapie it would lose its ability to affect humans.

  2. Affective and neuroendocrine stress reactivity to an academic examination: influence of the 5-HTTLPR genotype and trait neuroticism.

    Science.gov (United States)

    Verschoor, Ellen; Markus, C Rob

    2011-07-01

    The current study examined the singular and interactive effects of the 5-HTTLPR genotype and trait neuroticism on affective and physiological stress responses to an academic examination in healthy undergraduate students. From 771 students, 46 short/short (S/S)-allele carriers and 48 long/long (L/L)-allele carriers with the lowest and the highest neuroticism scores (80 females, 14 males; mean age±SD: 20.3±1.7 years) were selected. Salivary cortisol concentrations, mood and perceived stress were assessed before and after a 2-h written examination and compared with a control day. Negative mood, perceived stress and cortisol significantly increased during the examination compared to the control day. Negative stress effects on mood and perceived stress were significantly larger for S/S-allele carriers compared to L/L-allele carriers, regardless of trait neuroticism. Since vulnerability to real-life stressors is an important risk factor for depression pathogenesis, this may be a mediating factor making S/S-allele carriers more susceptible for depression symptoms.

  3. Metabolic composition of apple rootstock rhizodeposits differs in a genotype-specific manner and affects growth of subsequent plantings

    Science.gov (United States)

    The percolated rhizodeposit composition and quantity of 4 apple rootstock genotypes grown in sand was examined via liquid chromatography mass spectrometry time-of-flight, specifically contrasting the rhizodeposits of apple replant disease susceptible genotypes (M26, M9Nic29) with apple replant disea...

  4. Light, genotype, and abscisic acid affect chloroplast positioning in guard cells of Arabidopsis thaliana leaves in distinct ways.

    Science.gov (United States)

    Königer, Martina; Jessen, Brita; Yang, Rui; Sittler, Dorothea; Harris, Gary C

    2010-09-01

    The goal of this study was to investigate the effects of light intensity, genotype, and various chemical treatments on chloroplast movement in guard cells of Arabidopsis thaliana leaves. After treatment at various light intensities (dark, low, and high light), leaf discs were fixed with glutaraldehyde, and imaged using confocal laser microscopy. Each chloroplast was assigned a horizontal (close to pore, center, or epidermal side) and vertical (outer, middle, inner) position. White light had a distinct effect on chloroplast positioning, most notably under high light (HL) when chloroplasts on the upper leaf surface of wild-type (WT) moved from epidermal and center positions toward the pore. This was not the case for phot1-5/phot2-1 or phot2-1 plants, thus phototropins are essential for chloroplast positioning in guard cells. In npq1-2 mutants, fewer chloroplasts moved to the pore position under HL than in WT plants, indicating that white light can affect chloroplast positioning also in a zeaxanthin-dependent way. Cytochalasin B inhibited the movement of chloroplasts to the pore under HL, while oryzalin did not, supporting the idea that actin plays a role in the movement. The movement along actin cables is dependent on CHUP1 since chloroplast positioning in chup1 was significantly altered. Abscisic acid (ABA) caused most chloroplasts in WT and phot1-5/phot2-1 to be localized in the center, middle part of the guard cells irrespective of light treatment. This indicates that not only light but also water stress influences chloroplast positioning.

  5. Field-isolated genotypes of Mycobacterium bovis vary in virulence and influence case pathology but do not affect outbreak size.

    Directory of Open Access Journals (Sweden)

    David M Wright

    Full Text Available Strains of many infectious agents differ in fundamental epidemiological parameters including transmissibility, virulence and pathology. We investigated whether genotypes of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB differ significantly in transmissibility and virulence, combining data from a nine-year survey of the genetic structure of the M. bovis population in Northern Ireland with detailed records of the cattle population during the same period. We used the size of herd breakdowns as a proxy measure of transmissibility and the proportion of skin test positive animals (reactors that were visibly lesioned as a measure of virulence. Average breakdown size increased with herd size and varied depending on the manner of detection (routine herd testing or tracing of infectious contacts but we found no significant variation among M. bovis genotypes in breakdown size once these factors had been accounted for. However breakdowns due to some genotypes had a greater proportion of lesioned reactors than others, indicating that there may be variation in virulence among genotypes. These findings indicate that the current bTB control programme may be detecting infected herds sufficiently quickly so that differences in virulence are not manifested in terms of outbreak sizes. We also investigated whether pathology of infected cattle varied according to M. bovis genotype, analysing the distribution of lesions recorded at post mortem inspection. We concentrated on the proportion of cases lesioned in the lower respiratory tract, which can indicate the relative importance of the respiratory and alimentary routes of infection. The distribution of lesions varied among genotypes and with cattle age and there were also subtle differences among breeds. Age and breed differences may be related to differences in susceptibility and husbandry, but reasons for variation in lesion distribution among genotypes require further investigation.

  6. Genotype-by-Environment Interactions and Adaptation to Local Temperature Affect Immunity and Fecundity in Drosophila melanogaster

    Science.gov (United States)

    Lazzaro, Brian P.; Flores, Heather A.; Lorigan, James G.; Yourth, Christopher P.

    2008-01-01

    Natural populations of most organisms harbor substantial genetic variation for resistance to infection. The continued existence of such variation is unexpected under simple evolutionary models that either posit direct and continuous natural selection on the immune system or an evolved life history “balance” between immunity and other fitness traits in a constant environment. However, both local adaptation to heterogeneous environments and genotype-by-environment interactions can maintain genetic variation in a species. In this study, we test Drosophila melanogaster genotypes sampled from tropical Africa, temperate northeastern North America, and semi-tropical southeastern North America for resistance to bacterial infection and fecundity at three different environmental temperatures. Environmental temperature had absolute effects on all traits, but there were also marked genotype-by-environment interactions that may limit the global efficiency of natural selection on both traits. African flies performed more poorly than North American flies in both immunity and fecundity at the lowest temperature, but not at the higher temperatures, suggesting that the African population is maladapted to low temperature. In contrast, there was no evidence for clinal variation driven by thermal adaptation within North America for either trait. Resistance to infection and reproductive success were generally uncorrelated across genotypes, so this study finds no evidence for a fitness tradeoff between immunity and fecundity under the conditions tested. Both local adaptation to geographically heterogeneous environments and genotype-by-environment interactions may explain the persistence of genetic variation for resistance to infection in natural populations. PMID:18369474

  7. 谷胱甘肽转硫酶M1、T1基因型及烟酒嗜好与胃癌易感性的关系%Influence GSTM1 and GSTT1 Genotypes and Smoking, Alcohol Exposure on the Occurrence of Gastric Cancer: Case-control Study from Nanjing,China

    Institute of Scientific and Technical Information of China (English)

    沈孝兵; 浦跃朴; 张娇; 朱良军

    2005-01-01

    [目的]探讨谷胱甘肽转硫酶基因多态性M1(GSTM1)、T1(GSTT1)及烟酒嗜好与胃癌易感性的关系,并对GST基因多态性GSTT1、GSTM1与烟酒暴露在胃癌发生中的交互作用进行分析.[方法]采用1:1配对病例-对照研究方法和PCR技术,检测121例原发性胃癌患者和相应对照的GSTM1和GSTF1基因型,结合研究对象的烟酒嗜好,应用SAS统计分析系统,分析GSTM1和GSTT1基因型及烟酒暴露与胃癌发病的关系,并对基因-基因,基因-烟酒暴露在胃癌发生中的交互作用进行分析.[结果]GSTM1(-)基因型频率在病例组和对照组中分别占44.63%和33.88%,分布无显著性差异(x2=2.6436,P>0.05),GSTF1(-)基因型频率在病例组和对照组中分别为52.89%和44.63%,分布也无显著性差异(χ2=1.1650,P>0.05).吸烟者比非吸烟者发生胃癌的危险高(OR=2.538,95%CI:1.336~4.823);饮酒者比非饮酒者发生胃癌的危险高(oR=2.097,95%CI:1.025~4.291).同时携带GSTM1(-)和GSTT1(-)基因型者发生胃癌的危险性高于GSTM1(+)和GSTT1(+)基因型携带者(OR=2.097,95%CI:1.025~4.291);同时有烟酒嗜好的个体发生胃癌的危险性高于无烟酒嗜好者(OR=2.330,95%CI:1.211~4.482).携带GSTM1(-)和GSTT1(-)且有烟酒嗜好者,发生胃癌的危险显著高于携带GSTM1(+)和GSTT1(+)的无烟酒嗜好者(oR=3.600,95%CI:1.025~12.650).[结论]吸烟、饮酒与胃癌易感性增加有关,GSTM1和GSTT1基因型及烟酒嗜好在胃癌发生中存在一定的交互作用.%[Objective] To determine the association between glutathione-s-transferase genetic polymorphisms(GSTM1,GSTF1) and smoking, alcohol exposure with the risk of gastric cancer and elucidate the action and interaction of gene and environmental factors. [ Methods ] 1:1 Case-control study was conducted and polymerase chain reaction technique was employed to analyse the genetic polymorphisms of GST (GSTM1,GSTT1) genotype in 121 cases of patients with gastric cancer and sex, age

  8. Allele and genotype frequency of a genetic variant in ataxia telangiectasia mutated gene affecting glycemic response to metformin in South Indian population

    Directory of Open Access Journals (Sweden)

    Saranya Vilvanathan

    2014-01-01

    Full Text Available Allele and genotype frequency of a genetic variant in ATM gene affecting glycemic response to metformin in South Indian population . Context: The novel polymorphism in ATM gene (rs11212617, which is implicated to have association with metformin response, exhibits inter-ethnic variability in the allele and genotype frequency distribution . Aims and Design: The objective of the present study is to establish the allele and genotype frequency of rs11212617 single nucleotide polymorphism in ATM gene, in South Indian population and to find if this variant has any role in the etiology of type 2 diabetes mellitus . Materials and Methods: The study was performed in 2 cohorts of populations, 112 healthy volunteers and 118 type 2 diabetes mellitus patients. Genomic deoxyribonucleic acid (DNA was extracted from peripheral blood leucocytes by phenol-chloroform method and genotyping was performed by real-time polymerase chain reaction using TaqMan assay. Results: In South Indian population, the frequency of major A allele was 0.65 and the minor C allele was 0.35. AA and CC are the homozygous genotypes with frequency of 0.39 and 0.09 respectively. The frequency of heterozygous genotype AC (0.52 was found to be higher than the homozygotes. There was no significant difference in the frequency distribution in the diabetic population, which implies that this variant does not have any causative role in the disease etiology. The frequency distributions were found to be significantly different from the distributions in other ethnic populations such as Caucasians, Chinese, Japanese and Africans. But there was no significant difference when compared with the Gujarati Indians of Houston. Conclusion: The frequency distribution of this novel variant in South Indian population forms a framework for further gene disease association studies to establish the association of this variant with metformin response. Our study could not find any association of this variant with

  9. Phosphoglucose isomerase genotype affects running speed and heat shock protein expression after exposure to extreme temperatures in a montane willow beetle.

    Science.gov (United States)

    Rank, Nathan E; Bruce, Douglas A; McMillan, David M; Barclay, Colleen; Dahlhoff, Elizabeth P

    2007-03-01

    Eastern Sierra Nevada populations of the willow beetle Chrysomela aeneicollis commonly experience stressfully high and low environmental temperatures that may influence survival and reproduction. Allele frequencies at the enzyme locus phosphoglucose isomerase (PGI) vary across a climatic latitudinal gradient in these populations, with PGI allele 1 being most common in cooler regions and PGI allele 4 in warmer ones. PGI genotypes differ in heat and cold tolerance and in expression of a 70 kDa heat shock protein. Here we examine genetic, behavioral and environmental factors affecting a performance character, running speed, for willow beetles, and assess effects of consecutive cold and heat exposure on running speed and expression of Hsp70 in the laboratory. In nature, running speed depends on air temperature and is higher for males than females. Mating beetles ran faster than single beetles, and differences among PGI genotypes in male running speed depended on the presence of females. In the laboratory, exposure to cold reduced subsequent running speed, but the amount of this reduction depended on PGI genotype and previous thermal history. Effects of exposure to heat also depended on life history stage and PGI genotype. Adults possessing allele 1 ran fastest after a single exposure to stressful temperature, whereas those possessing allele 4 ran faster after repeated exposure. Larvae possessing allele 4 ran fastest after a single stressful exposure, but running speed generally declined after a second exposure to stressful temperature. The ranking of PGI genotypes after the second exposure depended on whether a larva had been exposed to cold or heat. Effects of temperature on Hsp70 expression also varied among PGI genotypes and depended on type of exposure, especially for adults (single heat exposure, two cold exposures: PGI 1-1>1-4>4-4; other multiple extreme exposures: 4-4>1-4>1-1). There was no consistent association between alleles at other polymorphic enzyme loci

  10. Sugar and Acid Content and Their Genotypic Correlations of Unselected P.Persica x P.Davidiana Progenies as Affected by Hairness and Flesh Color

    Institute of Scientific and Technical Information of China (English)

    WU Ben-hong; LI Shao-hua; Quilot Bénédicte; Génard Michel; Kervella Jocelyne

    2004-01-01

    Fruit sugar and acid content were determined in a group of hybrids from one family,including 22 peach and 85 nectarine genotypes, or 75 white-fleshed and 32 yellow-fleshed genotypes. Sucrose accounted for about 65% of the total sugar, and malate for about 50%of the total acid. Mean sucrose, fructose, sorbitol, total sugar, soluble solid and quinate content were significantly higher in nectarines than in peaches, while no significant difference was found in mean malate, citrate and total acid content between nectarines and peaches. Shikimate content was very low and ranged from 0.011-0.046 meq 100 g-1 FW in all genotypes studied. Flesh color did not affect sugar and acid content.Glucose and fructose had a close positive correlation (r=0.63***). Malate had positive correlations with sucrose, sorbitol, total sugar and soluble solid content. The correlation between citrate and sugars were not significant. Glucose, fructose, sorbitol and malate content seemed to be higher in late-maturing genotypes. Sucrose, total sugar and total acid content had a parabolic relationship with developmental period (from full blooming date to maturity date).

  11. Assimilation and Translocation of Dry Matter and Phosphorus in Rice Genotypes Affected by Salt-Alkaline Stress

    Directory of Open Access Journals (Sweden)

    Zhijie Tian

    2016-06-01

    Full Text Available Salt-alkaline stress generally leads to soil compaction and fertility decline. It also restricts rice growth and phosphorus acquisition. In this pot experiment, two relatively salt-alkaline tolerant (Dongdao-4 and Changbai-9 and sensitive (Changbai-25 and Tongyu-315 rice genotypes were planted in sandy (control and salt-alkaline soil to evaluate the characteristics of dry matter and phosphorus assimilation and translocation in rice. The results showed that dry matter and phosphorus assimilation in rice greatly decreased under salt-alkaline stress as the plants grew. The translocation and contribution of dry matter and phosphorus to the grains also increased markedly; different performances were observed between genotypes under salt-alkaline stress. D4 and C9 showed higher dry matter translocation, translocation efficiency and contribution of dry matter assimilation to panicles than those of C25 and T315. These changes in D4 and C9 indexes occurred at low levels of salt-alkaline treatment. Higher phosphorus acquisition efficiency of D4 and C9 were also found under salt-alkaline conditions. Additionally, the phosphorus translocation significantly decreased in C25 and T315 in the stress treatment. In conclusion, the results indicated that salt-alkaline-tolerant rice genotypes may have stronger abilities to assimilate and transfer biomass and phosphorus than sensitive genotypes, especially in salt-alkaline conditions.

  12. Angiotensin-converting enzyme gene I/D genotype affected metoprolol-induced reduction in 24-hour average heart rate

    Institute of Scientific and Technical Information of China (English)

    LIU Li-wei; LIU Hong; CHEN Guo-liang; HUANG Yi-ling; HAN Lu-lu; XU Zhi-min; JIANG Xiong-jing; LI Yi-shi

    2010-01-01

    Background Genetic factors can influence antihypertensive response to metoprolol, and many studies focused on the relationship between the genotype in β1-adrenergic receptor and blood pressure (BP), little was known about the association of angiotensin-converting enzyme (ACE) genotype with the therapeutic result of metoprolol. The present study aimed to investigate whether the ACE gene insertion (I) / deletion (D) polymorphism Is related to the response to metoprolol in Chinese Han hypertensive patients.Methods Ninety-six patients with essential hypertension received metoprolol (100 mg once daily) as monotherapy for 8 weeks. Twenty-four hours ambulatory blood pressure monitoring and dynamic electrocardiogram were performed before and after treatment. Genotyping analysis was performed using PCR. The association of the ACE gene I/D polymorphism with variations in BP and heart rate (HR) was observed after the 8-week treatment.Results The patients with ACE gene II polymorphism showed greater reduction in 24-hour average HR than those with ID or DD polymorphisms (P=0.045), no effect of this genotype on the reduction in seating HR or in BP was observed. After adjusting for age, gender, body mass index, BP and HR at baseline, the ACE gene I/D polymorphism was still an independent predictor for variations in 24-hour average HR.Conclusions The II polymorphism in ACE gene could be a candidate predictor for greater reduction in 24-hour average HR in Chinese Han hypertensive patients treated by metoprolol. Greater benefits would be obtained by patients with II polymorphism from the treatment with metoprolol. Larger studies are warranted to validate this finding.

  13. Genotype on the Pigmentation Regulating PMEL17 Gene Affects Behavior in Chickens Raised Without Physical Contact with Conspecifics

    OpenAIRE

    Karlsson, Anna-Carin; Mormede, Pierre; Kerje, Susanne; Jensen, Per

    2011-01-01

    Chickens homozygous for the Dominant white or wild-type allele of PMEL17 were subjected to a broad phenotyping in order to detect consistent differences between genotypes. To exclude feather pecking, the chickens were individually housed without physical contact, from the day of hatching, and tested for social, aggressive, fear and exploratory behaviors, and corticosterone and testosterone levels were assessed. In a principal component analysis, 53.2% of the behavior variation was explained b...

  14. Carcass morphology and meat quality from roosters slaughtered at eight months affected by genotype and finishing feeding

    Directory of Open Access Journals (Sweden)

    D. Franco

    2013-04-01

    Full Text Available The aim of this study was to describe the carcass characteristics and the meat quality of the roosters from the autochthonous Mos breed slaughtered at 8 months. With comparative purpose roosters from hybrid line Sasso T44 were used in this study. Birds were reared on their typical production system (extensive indoor or barns and finishing diet whit corn. Both live and carcass weight were higher for commercial breed (p<0.001. Drumstick, thigh and wing percentages were greater in Mos breed than in Sasso T-44, while breast was similar for both genotypes. Only significant differences in cholesterol and alpha-tocopherol content between genotypes have been found, whereas finishing feeding treatment had effect on moisture, intramuscular fat content, cholesterol, tocopherol isomers and meat yellowness. Unsaturated fatty acids constituted the main contribution to total amount of fatty acid (FA, where monounsaturated oleic acid was the major compound, and found higher concentrations in commercial breed. Mos breed showed higher amounts of polyunsaturated fatty acids (PUFA and lower amounts of monounsaturated fatty acids (MUFA than Sasso T-44. The relation PUFA/SFA was above 0.68 for Mos breed and was slightly lower for the other genotype. In conclusion, the carcass morphology and meat quality was influenced by breed and finishing feeding with corn.

  15. Desmanthus GENOTYPES

    Directory of Open Access Journals (Sweden)

    JOSÉ HENRIQUE DE ALBUQUERQUE RANGEL

    2015-01-01

    Full Text Available Desmanthus is a genus of forage legumes with potential to improve pastures and livestock produc-tion on clay soils of dry tropical and subtropical regions such as the existing in Brazil and Australia. Despite this patterns of natural or enforced after-ripening of Desmanthus seeds have not been well established. Four year old seed banks of nine Desmanthus genotypes at James Cook University were accessed for their patterns of seed softe-ning in response to a range of temperatures. Persistent seed banks were found to exist under all of the studied ge-notypes. The largest seeds banks were found in the genotypes CPI 78373 and CPI 78382 and the smallest in the genotypes CPI’s 37143, 67643, and 83563. An increase in the percentage of softened seeds was correlated with higher temperatures, in two patterns of response: in some accessions seeds were not significantly affected by tempe-ratures below 80º C; and in others, seeds become soft when temperature rose to as little as 60 ºC. At 80 °C the heat started to depress germination. High seed production of Desmanthus associated with dependence of seeds on eleva-ted temperatures to softening can be a very important strategy for plants to survive in dry tropical regions.

  16. 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.

  17. Factors that affect proliferation of Salmonella in tomatoes post-harvest: the roles of seasonal effects, irrigation regime, crop and pathogen genotype.

    Science.gov (United States)

    Marvasi, Massimiliano; Hochmuth, George J; Giurcanu, Mihai C; George, Andrée S; Noel, Jason T; Bartz, Jerry; Teplitski, Max

    2013-01-01

    Fresh fruits and vegetables become increasingly recognized as vehicles of human salmonellosis. Physiological, ecological, and environmental factors are all thought to contribute to the ability of Salmonella to colonize fruits and vegetables pre- and post-harvest. The goal of this study was to test how irrigation levels, fruit water congestion, crop and pathogen genotypes affect the ability of Salmonella to multiply in tomatoes post-harvest. Fruits from three tomato varieties, grown over three production seasons in two Florida locations, were infected with seven strains of Salmonella and their ability to multiply post-harvest in field-grown tomatoes was tested. The field experiments were set up as a two-factor factorial split plot experiment, with the whole-plot treatments arranged in a randomized complete-block design. The irrigation treatment (at three levels) was the whole-plot factor, and the split-plot factor was tomato variety, with three levels. The significance of the main, two-way, and three-way interaction effects was tested using the (type III) F-tests for fixed effects. Mean separation for each significant fixed effect in the model was performed using Tukey's multiple comparison testing procedure. The irrigation regime per se did not affect susceptibility of the crop to post-harvest proliferation of Salmonella. However, Salmonella grew significantly better in water-congested tissues of green tomatoes. Tomato maturity and genotype, Salmonella genotype, and inter-seasonal differences were the strongest factors affecting proliferation. Red ripe tomatoes were significantly and consistently more conducive to proliferation of Salmonella. Tomatoes harvested in the driest, sunniest season were the most conducive to post-harvest proliferation of the pathogen. Statistically significant interactions between production conditions affected post-harvest susceptibility of the crop to the pathogen. UV irradiation of tomatoes post-harvest promoted Salmonella growth.

  18. Factors that affect proliferation of Salmonella in tomatoes post-harvest: the roles of seasonal effects, irrigation regime, crop and pathogen genotype.

    Directory of Open Access Journals (Sweden)

    Massimiliano Marvasi

    Full Text Available MAIN OBJECTIVES: Fresh fruits and vegetables become increasingly recognized as vehicles of human salmonellosis. Physiological, ecological, and environmental factors are all thought to contribute to the ability of Salmonella to colonize fruits and vegetables pre- and post-harvest. The goal of this study was to test how irrigation levels, fruit water congestion, crop and pathogen genotypes affect the ability of Salmonella to multiply in tomatoes post-harvest. EXPERIMENTAL DESIGN: Fruits from three tomato varieties, grown over three production seasons in two Florida locations, were infected with seven strains of Salmonella and their ability to multiply post-harvest in field-grown tomatoes was tested. The field experiments were set up as a two-factor factorial split plot experiment, with the whole-plot treatments arranged in a randomized complete-block design. The irrigation treatment (at three levels was the whole-plot factor, and the split-plot factor was tomato variety, with three levels. The significance of the main, two-way, and three-way interaction effects was tested using the (type III F-tests for fixed effects. Mean separation for each significant fixed effect in the model was performed using Tukey's multiple comparison testing procedure. MOST IMPORTANT DISCOVERIES AND SIGNIFICANCE: The irrigation regime per se did not affect susceptibility of the crop to post-harvest proliferation of Salmonella. However, Salmonella grew significantly better in water-congested tissues of green tomatoes. Tomato maturity and genotype, Salmonella genotype, and inter-seasonal differences were the strongest factors affecting proliferation. Red ripe tomatoes were significantly and consistently more conducive to proliferation of Salmonella. Tomatoes harvested in the driest, sunniest season were the most conducive to post-harvest proliferation of the pathogen. Statistically significant interactions between production conditions affected post-harvest susceptibility

  19. Physiological and affective reactivity to a 35% CO₂ inhalation challenge in individuals differing in the 5-HTTLPR genotype and trait neuroticism.

    Science.gov (United States)

    Verschoor, Ellen; Markus, C Rob

    2012-08-01

    The inhalation of 35% carbon dioxide (CO₂) results in an acute stress response in healthy individuals and may accordingly provide a good paradigm to examine potential vulnerability factors for stress reactivity and stress-related psychopathology. It has been proposed that CO₂ reactivity is moderated by genetic (5-HTTLPR) and personality (neuroticism) factors, yet no experimental study has investigated their effects on CO₂ reactivity simultaneously. The current study examined the singular and interactive effects of the 5-HTTLPR genotype and neuroticism in predicting the affective and physiological response to a 35% CO₂ challenge in a healthy sample of male and female students. From a large group of 771 students, 48 carriers of the low/low expressing allele (S/S, S/Lg, Lg/Lg) and 48 carriers of the high/high expressing allele (La/La) with the lowest and the highest neuroticism scores (77 females, 19 males; mean age ± SD: 20.6 ± 2 years) were selected and underwent a 35% CO₂ inhalation. Visual analogue scales for anxiety and discomfort and the Panic Symptom List were used to assess affective symptomatology, while salivary samples and heart rate were assessed to establish the physiological response. A typical pattern of responses to CO₂ was observed, characterised by increases in anxiogenic symptoms and physical panic symptomatology and a reduction in heart rate; however, no effect on salivary cortisol concentration was observed. Additionally, the CO₂ reactivity did not differ between groups divided by the 5-HTTLPR genotype or neuroticism. Findings of the current study do not support a role for singular or interactive effects of the 5-HTTLPR genotype and trait neuroticism on affective and physiological reactivity to a 35% CO₂ inhalation procedure.

  20. Maturity stages affect the postharvest quality and shelf-life of fruits of strawberry genotypes growing in subtropical regions

    Directory of Open Access Journals (Sweden)

    M. Moshiur Rahman

    2016-01-01

    Full Text Available The postharvest changes of five promising strawberry genotypes viz. Sweet Charlie, Festival, Camarosa, FA 008 and BARI Strawberry-1 at ambient temperature were studied under sub tropical region during the winter season (December–April of 2010–2011 and 2011–2012 in Bangladesh. Irrespective of maturity stages percent fruit decay and weight of fruits were noted minimum in Camarosa and maximum in FA 008 up to day 4 of storage. The shelf life of fruits was maximum in Camarosa and minimum in FA 008 and BARI Strawberry-1 regardless of maturity stage throughout the storage period. The TSS, total sugar and ascorbic acid content of fruits were increased with the increase in maturity stage during the storage period. In 1/3rd and 2/3rd maturity stages, the TSS and total sugar content were found the highest in Festival but at full maturity stage those were recorded higher in Camarosa. The titratable acidity was noticed the highest in 1/3rd matured fruits and gradually decreased with the increase in maturity stage as well as storage duration in all the genotypes. Ascorbic acid content of strawberry gradually decreases during the storage period. Fully matured fresh fruits of Festival contained maximum ascorbic acid content while BARI Strawberry-1 contained minimum ascorbic acid that was reduced after 3 days of storage.

  1. M$_1$ - M* correlation in galaxy clusters

    CERN Document Server

    Trevese, D; Appodia, B

    1994-01-01

    Photographic F band photometry of a sample of 36 Abell clusters has been used to study the relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M^*. Clusters appear segregated in the M_1-M^* plane according to their Rood \\& Sastry class. We prove on a statistical basis that on average, going from early to late RS classes, M_1 becomes brighter while M^* becomes fainter. The result agrees with the predictions of galactic cannibalism models, never confirmed by previous analyses.

  2. Isothiocyanates, Nitriles, and Epithionitriles from Glucosinolates Are Affected by Genotype and Developmental Stage in Brassica oleracea Varieties

    Directory of Open Access Journals (Sweden)

    Franziska S. Hanschen

    2017-06-01

    Full Text Available Vegetables of the Brassica oleracea group, such as broccoli, cauliflower, and cabbage, play an important role for glucosinolate consumption in the human diet. Upon maceration of the vegetable tissue, glucosinolates are degraded enzymatically to form volatile isothiocyanates, nitriles, and epithionitriles. However, only the uptake of isothiocyanates is linked to the cancer-preventive effects. Thus, it is of great interest to evaluate especially the isothiocyanate formation. Here, we studied the formation of glucosinolates and their respective hydrolysis products in sprouts and fully developed vegetable heads of different genotypes of the five B. oleracea varieties: broccoli, cauliflower as well as white, red, and savoy cabbages. Further, the effect of ontogeny (developmental stages during the head development on the formation of glucosinolates and their respective hydrolysis products was evaluated at three different developmental stages (mini, fully developed, and over-mature head. Broccoli and red cabbage were mainly rich in 4-(methylsulfinylbutyl glucosinolate (glucoraphanin, whereas cauliflower, savoy cabbage and white cabbage contained mainly 2-propenyl (sinigrin and 3-(methylsulfinylpropyl glucosinolate (glucoiberin. Upon hydrolysis, epithionitriles or nitriles were often observed to be the main hydrolysis products, with 1-cyano-2,3-epithiopropane being most abundant with up to 5.7 μmol/g fresh weight in white cabbage sprouts. Notably, sprouts often contained more than 10 times more glucosinolates or their hydrolysis products compared to fully developed vegetables. Moreover, during head development, both glucosinolate concentrations as well as hydrolysis product concentrations changed and mini heads contained the highest isothiocyanate concentrations. Thus, from a cancer-preventive point of view, consumption of mini heads of the B. oleracea varieties is recommended.

  3. Genetic Polymorphisms Analysis of Glutathione S-transferase M1 and T1 in Children with Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    王军; 张利; 冯建飞; 王宏; 朱绍先; 胡豫; 李玉香

    2004-01-01

    Summary: The relationship between glutathione S-transferases (GSTs) M1, T1 genotype and childhood acute lymphoblastic leukemia (ALL) was investigated. GSTM1 and GSTT1 genotypes in genomic DNA from 67 children with ALL and 146 healthy controls were analyzed by using the multiplex polymerase chain reaction (PCR). The frequencies of GSTM1, M1-T1 null genotypes in ALL children were significantly higher than in the healthy controls (76.12 % versus 52.74 %, OR=2.856, P<0.001;50. 74 % versus 24. 66 %, OR=3. 148, P<0.001, respectively). However,there was no significant relationship between GSTT1 null genotype and ALL of children (61.19 %versus 49.32 %, OR=1. 621, P>0.05). It was suggested that GSTM1 null genotype might be a risk genotype of childhood ALL, while there as no correlation between GSTT1 null genotype and childhood ALL.

  4. GxE Interactions Between FOXO Genotypes and Tea Drinking Significantly Affect Cognitive Disability at Advanced Ages in China

    DEFF Research Database (Denmark)

    Zeng, Yi; Chen, Huashuai; Ni, Ting

    2015-01-01

    age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health...... benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles....

  5. Characterization of Compass M-1 signals

    NARCIS (Netherlands)

    Hauschild, A.; Montenbruck, O.; Sleewaegen, J.-M.; Huisman, L.; Teunissen, P.J.G.

    2011-01-01

    An analysis of observations from China’s first medium earth orbit satellite Compass M-1 is presented, with main focus on the first orbit and clock solution for this satellite. The orbit is computed from laser ranging measurements. Based on this orbit solution, the apparent clock offset is estimated

  6. Analytic closures for M1 neutrino transport

    Science.gov (United States)

    Murchikova, E. M.; Abdikamalov, E.; Urbatsch, T.

    2017-08-01

    Carefully accounting for neutrino transport is an essential component of many astrophysical studies. Solving the full transport equation is too expensive for most realistic applications, especially those involving multiple spatial dimensions. For such cases, resorting to approximations is often the only viable option for obtaining solutions. One such approximation, which recently became popular, is the M1 method. It utilizes the system of the lowest two moments of the transport equation and closes the system with an ad hoc closure relation. The accuracy of the M1 solution depends on the quality of the closure. Several closures have been proposed in the literature and have been used in various studies. We carry out an extensive study of these closures by comparing the results of M1 calculations with precise Monte Carlo calculations of the radiation field around spherically symmetric protoneutron star models. We find that no closure performs consistently better or worse than others in all cases. The level of accuracy that a given closure yields depends on the matter configuration, neutrino type and neutrino energy. Given this limitation, the maximum entropy closure by Minerbo on average yields relatively accurate results in the broadest set of cases considered in this work.

  7. CYP2C9 genotype does not affect risk of tobacco-related cancer in the general population

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Nordestgaard, B.G.; Bojesen, S.E.

    2010-01-01

    tolbutamide and warfarin, while this has not been investigated for PAHs. We hypothesised that these two variants in the CYP2C9 gene influence risk of tobacco-related cancer. Methods: In a prospective study of the general population (n = 10 392) with 60 years of follow-up, the Copenhagen City Heart Study, we.......9/1.1 in the Copenhagen City Heart Study and below/above 0.8/1.3 and 0.9/1.1 in the Copenhagen General Population Study for tobacco-related cancer and all cancer, respectively. Conclusion: Genetic variations in CYP2C9 do not affect risk of tobacco-related cancers. (C) 2010 Elsevier Ltd. All rights reserved...... associated two variants of CYP2C9 (CYP2C9*2 and CYP2C9*3) with risk of tobacco-related cancer and all cancer. All results were re-tested in a cross-sectional study of the general population (n = 36 856), the Copenhagen General Population Study. Results: We found no association between any of the CYP2C9...

  8. Selectivity of oxomemazine for the M1 muscarinic receptors.

    Science.gov (United States)

    Lee, S W; Woo, C W; Kim, J G

    1994-12-01

    The binding characteristics of pirenzepine and oxomemazine to muscarinic receptor were studied to evaluate the selectivity of oxomemazine for the muscarinic receptor subtypes in rat cerebral microsomes. Equilibrium dissociation constant (KD) of (-)-[3H]quinuclidinyl benzilate([3H]QNB) determined from saturation isotherms was 64 pM. Analysis of the pirenzepine inhibition curve of [3H]QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki = 16 nM, M1 receptor) and low (Ki = 400 nM, M3 receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with about 20-fold difference in the affinity for high (Ki = 84 nM, OH receptor) and low (Ki = 1.65 microM, OL receptor) affinity sites. The percentage populations of M1 and M3 receptors to the total receptors were 61:39, and those of OH and OL receptors 39:61, respectively. Both pirenzepine and oxomemazine increased the KD value for [3H]QNB without affecting the binding site concentrations and Hill coefficient for the [3H]QNB binding. Oxomemazine had a 10-fold higher affinity at M1 receptors than at M3 receptors, and pirenzepine a 8-fold higher affinity at OH receptors than at OL receptors. Analysis of the shallow competition binding curves of oxomemazine for M1 receptors and pirenzepine for OL receptors yielded that 69% of M1 receptors were of OH receptors and the remaining 31% of OL receptors, and that 29% of OL receptors were of M1 receptors and 71% of M3 receptors. However, M3 for oxomemazine and OH for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could be classified as a selective drug for M1 receptors and also demonstrate that rat cerebral microsomes contain three different subtypes of M1, M3 and the other site which is different from M1, M2 and M3 receptors.

  9. Spatial and temporal factors affecting parasite genotypes encountered by hosts: empirical data from American dog ticks (Dermacentor variabilis) parasitising raccoons (Procyon lotor).

    Science.gov (United States)

    Dharmarajan, G; Beasley, J C; Rhodes, O E

    2010-06-01

    The American dog tick (Dermacentor variabilis) is an important vector of numerous pathogens of humans and animals. In this study, we analysed population genetic patterns in D. variabilis at scales of the host individual (infrapopulation) and population (component population) to elucidate fine-scale spatial and temporal factors influencing transmission dynamics. We genotyped D. variabilis collected from raccoons (Procyon lotor) trapped in two habitat patches (located in Indiana, USA) which were spatially proximate (5.9 km) and limited in size (10.48 Ha and 25.47 Ha, respectively). Despite the fine spatial sampling scale, our analyses revealed significant genetic differentiation amongst component populations and infrapopulations (within each component population), indicating a non-random pattern of encountering tick genotypes by raccoons at both scales evaluated. We found evidence for male-biased dispersal in the ticks themselves (in one component population) and an age-bias in spatial scales at which raccoons encountered ticks in the environment. At the scale of the component population, our analyses revealed that raccoons encountered ticks from a limited number of D. variabilis family groups, likely due to high reproductive variance amongst individual ticks. Finally, we found evidence for a temporal effect with raccoons encountering ticks in the environment as "clumps" of related individuals. While the genetic structure of parasite populations are increasingly being investigated at small spatial scales (e.g. the infrapopulation), our data reveal that genetic structuring can originate at scales below that of the infrapopulation, due to the interaction between temporal and biological factors affecting the encounter of parasites by individual hosts. Ultimately, our data indicate that genetic structure in parasites must be viewed as a consequence of both spatial and temporal variance in host-parasite interactions, which in turn are driven by demographic factors related

  10. Dopamine transporter SLC6A3 genotype affects cortico-striatal activity of set-shifts in Parkinson’s disease

    Science.gov (United States)

    Habak, Claudine; Noreau, Anne; Nagano-Saito, Atsuko; Mejía-Constaín, Beatriz; Degroot, Clotilde; Strafella, Antonio P.; Chouinard, Sylvain; Lafontaine, Anne-Louise; Rouleau, Guy A.

    2014-01-01

    Parkinson’s disease is a neurodegenerative condition that affects motor function along with a wide range of cognitive domains, including executive function. The hallmark of the pathology is its significant loss of nigrostriatal dopamine, which is necessary for the cortico-striatal interactions that underlie executive control. Striatal dopamine reuptake is mediated by the SLC6A3 gene (formerly named DAT1) and its polymorphisms, which have been largely overlooked in Parkinson’s disease. Thirty patients (ages 53–68 years; 19 males, 11 females) at early stages of Parkinson’s disease, were genotyped according to a 9-repeat (9R) or 10-repeat (10R) allele on the SLC6A3/DAT1 gene. They underwent neuropsychological assessment and functional magnetic resonance imaging while performing a set-shifting task (a computerized Wisconsin Card Sorting Task) that relies on fronto-striatal interactions. Patients homozygous on the 10R allele performed significantly better on working memory tasks than 9R-carrier patients. Most importantly, patients carrying a 9R allele exhibited less activation than their 10R homozygous counterparts in the prefrontal cortex, premotor cortex and caudate nucleus, when planning and executing a set-shift. This pattern was exacerbated for conditions that usually recruit the striatum compared to those that do not. This is the first study indicating that the SLC6A3/DAT1 genotype has a significant effect on fronto-striatal activation and performance in Parkinson’s disease. This effect is stronger for conditions that engage the striatum. Longitudinal studies are warranted to assess this polymorphism’s effect on the clinical evolution of patients with Parkinson’s disease, especially with cognitive decline. PMID:25212851

  11. Effects of citalopram and escitalopram on fMRI response to affective stimuli in healthy volunteers selected by serotonin transporter genotype.

    Science.gov (United States)

    Henry, Michael E; Lauriat, Tara L; Lowen, Steven B; Churchill, Jeffrey H; Hodgkinson, Colin A; Goldman, David; Renshaw, Perry F

    2013-09-30

    This study was designed to assess whether functional magnetic resonance imaging (fMRI) following antidepressant administration (pharmaco-fMRI) is sufficiently sensitive to detect differences in patterns of activation between enantiomers of the same compound. Healthy adult males (n=11) participated in a randomized, double-blind, cross-over trial with three medication periods during which they received citalopram (racemic mixture), escitalopram (S-citalopram alone), or placebo for 2 weeks. All participants had high expression serotonin transporter genotypes. An fMRI scan that included passive viewing of overt and covert affective faces and affective words was performed after each medication period. Activation in response to overt faces was greater following escitalopram than following citalopram in the right insula, thalamus, and putamen when the faces were compared with a fixation stimulus. For the rapid covert presentation, a greater response was observed in the left middle temporal gyrus in the happy versus fearful contrast following escitalopram than following citalopram. Thus, the combination of genomics and fMRI was successful in discriminating between two very similar drugs. However, the pattern of activation observed suggests that further studies are indicated to understand how to optimally combine the two techniques.

  12. M1 muscarinic receptor activation mediates cell death in M1-HEK293 cells.

    Science.gov (United States)

    Graham, E Scott; Woo, Kerhan K; Aalderink, Miranda; Fry, Sandie; Greenwood, Jeffrey M; Glass, Michelle; Dragunow, Mike

    2013-01-01

    HEK293 cells have been used extensively to generate stable cell lines to study G protein-coupled receptors, such as muscarinic acetylcholine receptors (mAChRs). The activation of M1 mAChRs in various cell types in vitro has been shown to be protective. To further investigate M1 mAChR-mediated cell survival, we generated stable HEK293 cell-lines expressing the human M1 mAChR. M1 mAChRs were efficiently expressed at the cell surface and efficiently internalised within 1 h by carbachol. Carbachol also induced early signalling cascades similar to previous reports. Thus, ectopically expressed M1 receptors behaved in a similar fashion to the native receptor over short time periods of analysis. However, substantial cell death was observed in HEK293-M1 cells within 24 h after carbachol application. Death was only observed in HEK cells expressing M1 receptors and fully blocked by M1 antagonists. M1 mAChR-stimulation mediated prolonged activation of the MEK-ERK pathway and resulted in prolonged induction of the transcription factor EGR-1 (>24 h). Blockade of ERK signalling with U0126 did not reduce M1 mAChR-mediated cell-death significantly but inhibited the acute induction of EGR-1. We investigated the time-course of cell death using time-lapse microscopy and xCELLigence technology. Both revealed the M1 mAChR cytotoxicity occurs within several hours of M1 activation. The xCELLigence assay also confirmed that the ERK pathway was not involved in cell-death. Interestingly, the MEK blocker did reduce carbachol-mediated cleaved caspase 3 expression in HEK293-M1 cells. The HEK293 cell line is a widely used pharmacological tool for studying G-protein coupled receptors, including mAChRs. Our results highlight the importance of investigating the longer term fate of these cells in short term signalling studies. Identifying how and why activation of the M1 mAChR signals apoptosis in these cells may lead to a better understanding of how mAChRs regulate cell-fate decisions.

  13. Association between CYP1A1m1 gene polymorphism and primary open-angle glaucoma.

    Science.gov (United States)

    Costa, N B; Silva, C T X; Frare, A B; Silva, R E; Moura, K K V O

    2014-12-04

    The CYP1A1 gene is related to the generation of secondary metabolites that are capable of inducing DNA damage. The CYP1A1m1 polymorphism has been examined in many studies, and is located in a region near loci that have been linked to glaucoma, including the locus GLC1I. As a result, this polymorphism has been related to several diseases that are influenced by exposure to xenobiotic as well as primary open-angle glaucoma. We compared the prevalence of the CYP1A1m1 polymorphism in 152 Brazilian patients, 100 patients with primary open-angle glaucoma, and 52 normal controls using restriction fragment length polymorphism analysis. The frequency of the homozygous wild-type (w1/w1) CYP1A1 gene among patients with primary open-angle glaucoma (N = 100) was 16%, for genotype w1/m1, the frequency was 77%, and for m1/m1 it was 7%. Among the control group (N = 52), the frequency of the homozygous wild-type (w1/w1) CYP1A1 gene was 54%, the frequency of w1/m1 was 46%, and the frequency of m1/m1 was 0%. The presence of the CYP1A1m1 polymorphism may interfere with xenobiotic metabolism and exacerbate direct or indirect damage to the optic nerve. These CYP1A1m1 polymorphisms may be risk factors for primary open-angle glaucoma.

  14. "m=1" coatings for neutron guides

    OpenAIRE

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt; Kapaklis, V.; Wilkens, H.; Rats, D.; Hjörvarsson, B.; Kirstein, O.; Bentley, Philip

    2014-01-01

    A substantial part of the price for a neutron guide is the shielding needed because of the gamma ray produced when neutrons are absorbed. This absorption occurs in the coating and the substrate of the neutron guides. Traditional m=1 coatings have been made of Ni and if reflectivity over the critical angle of Ni is needed one has used Ni58 or Ni/Ti multilayer coatings. Ni has one of the highest neutron scattering density but it also has a fairly high absorption cross section for cold and therm...

  15. "m=1" coatings for neutron guides

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt

    2014-01-01

    A substantial part of the price for a neutron guide is the shielding needed because of the gamma ray produced when neutrons are absorbed. This absorption occurs in the coating and the substrate of the neutron guides. Traditional m=1 coatings have been made of Ni and if reflectivity over...... the critical angle of Ni is needed one has used Ni58 or Ni/Ti multilayer coatings. Ni has one of the highest neutron scattering density but it also has a fairly high absorption cross section for cold and thermal neutrons and when a neutron is absorbed it emits a lot of gamma rays, some with energies above 9 Me......V. Materials like diamond and Be have higher neutron scattering density than Ni, have smaller absorption cross section and when a neutron is absorbed they emit much less gamma ray and at lower energies. We present results, both theoretically and experimentally, comparing Ni with Be and preliminary results...

  16. Cancer risks posed by aflatoxin M1.

    Science.gov (United States)

    Hsieh, D P; Cullen, J M; Hsieh, L S; Shao, Y; Ruebner, B H

    1985-01-01

    The suspect milk-borne carcinogen, aflatoxin M1 (AFM), was produced and isolated from the rice culture of the fungus Aspergillus flavus NRRL3251 for confirmation and determination of the potency of its carcinogenicity in the male adult Fischer rat. The carcinogen was mixed into an agar-based, semisynthetic diet at 0, 0.5, 5, and 50 ppb (microgram/kg) and was fed to groups of animals continuously for 19-21 months. Aflatoxin B1 (AFB), of which AFM is a metabolite, at 50 ppb was used as a positive control. Hepatocarcinogenicity of AFM was detected at 50 ppb, but not at 5 or 0.5 ppb, with a potency of 2-10% that of AFB. A low incidence of intestinal adenocarcinomas was found in the AFM 50 ppb group, but not in any other groups. At 0.5 ppb, the action level enforced by the U.S.A. Food and Drug Administration, AFM induced no liver lesions in the rats but stimulated the animals' growth. On the average, the rats in the 0.5 ppb group weighed 11% (p less than 0.001) more than those in the control group. This increased growth was associated with increased feed intake. Based on the biological activity of AFM at the relevant low doses and the estimated level of human exposure to AFM through consumption of milk, the cancer risk posed by this contaminant for human adults is assessed to be very low. For infants, further studies are warranted because milk constitutes the major ingredient of the infant diet and because infant animals have been shown to be more sensitive to the carcinogenicity of AFB than adult animals.

  17. Phytosiderophore release by wheat genotypes differing in zinc deficiency tolerance grown with Zn-free nutrient solution as affected by salinity.

    Science.gov (United States)

    Daneshbakhsh, Bahareh; Khoshgoftarmanesh, Amir Hossein; Shariatmadari, Hossein; Cakmak, Ismail

    2013-01-01

    There is limited information concerning the effect of salinity on phytosiderophores exudation from wheat roots. The aim of this hydroponic experiment was to investigate the effect of salinity on phytosiderophore release by roots of three bread wheat genotypes differing in Zn efficiency (Triticum aestivum L. cvs. Rushan, Kavir, and Cross) under Zn deficiency conditions. Wheat seedlings were transferred to Zn-free nutrient solutions and exposed to three salinity levels (0, 60, and 120 mM NaCl). The results indicated that Cross and Rushan genotypes exuded more phytosiderophore than did the Kavir genotype. Our findings suggest that the adaptive capacity of Zn-efficient 'Cross' and 'Rushan' wheat genotypes to Zn deficiency is due partly to the higher amounts of phytosiderophore release. Only 15 days of Zn deficiency stress was sufficient to distinguish between Zn-efficient (Rushan and Cross) and Zn-inefficient (Kavir) genotypes, with the former genotypes exuding more phytosiderophore than the latter. Higher phytosiderophore exudation under Zn deficiency conditions was accompanied by greater Fe transport from root to shoot. The maximum amount of phytosiderophore was exuded at the third week in 'Cross' and at the fourth week in 'Kavir' and 'Rushan'. For all three wheat genotypes, salinity stress resulted in higher amounts of phytosiderophore exuded by the roots. In general, for 'Kavir', the largest amount of phytosiderophore was exuded from the roots at the highest salinity level (120mM NaCl), while for 'Cross' and 'Rushan', no significant difference was found in phytosiderophore exudation between the 60 and 120 mM NaCl treatments. More investigation is needed to fully understand the physiology of elevated phytosiderophore release by Zn-deficient wheat plants under salinity conditions.

  18. Methylenetetrahydrofolate reductase C677T genotype affects promoter methylation of tumor-specific genes in sporadic colorectal cancer through an interaction with folate/vitamin B12 status

    Institute of Scientific and Technical Information of China (English)

    Pooneh Mokarram; Fakhraddin Naghibalhossaini; Mehdi Saberi Firoozi; Seyed Vahid Hosseini; Ahmad Izadpanah; Heshmetalah Salahi; Seyed Ali Malek-Hosseini; Abdoulrasool Talei; Mehra Mojallal

    2008-01-01

    AIM: To evaluate joint effects of Methy/entetra-hydrofolate reductase (MTHFR) C677Tgenotypes, and serum folate/vitamin B12 concentrations on promoter methylation of tumor-associated genes among Iranian colorectal cancer patients.METHODS: We examined the associations between MTHFR C677T genotype, and promoter methylation of P16, Hmlh1, and Hmsh2 tumor-related genes amonq 151 sporadic colorectal cancer patients. The promoter methylation of tumor-related genes was determined by methylation-specific PCR. Eighty six patients from whom fresh tumor samples were obtained and 81 controls were also examined for serum folate and vitamin B12, concentrations by a commercia radioimmunoassay kit.RESULTS: We found 29.1% of cases had tumors with at least one methylated gene promoter. In case-case comparison, we did not find a significant association between methylation in tumors and any single genotype. However, in comparison to controls with the CC genotype, an increased risk of tumor methylation was associated with the CT genotype (OR=2.5;95% CI,1.1-5.6). In case-case comparisons, folate/vitamin B12 levels were positively associated with tumor methylation. Adjusted odds ratios for tumor methylation in cases with high (above median) versus low (below median) serum folate/vitamin B12 levels were 4.9 (95% CI,1.4-17.7), and 3.9 (95% CI,1.1-13.9), respectively. The frequency of methylated tumors was significantly higher in high methyl donor than low methyl donor group, especially in those with MTHFR CT (P=0.01), and CT/TT (P=0.002) genotypes, but not in those with the CC genotype (P=1.0).CONCLUSION: We conclude that high concentrations of serum folate/vitamin B12 levels are associated with the risk of promoter methylation in tumor-specific genes, and this relationship is modified by MTHFR C677T genotypes.

  19. On the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, complex orthogonal design

    CERN Document Server

    Li, Yuan

    2011-01-01

    Complex orthogonal designs (CODs) are used to construct space-time block codes. COD $\\mathcal{O}_z$ with parameter $[p, n, k]$ is a $p\\times n$ matrix, where nonzero entries are filled by $\\pm z_i$ or $\\pm z^*_i$, $i = 1, 2,..., k$, such that $\\mathcal{O}^H_z \\mathcal{O}_z = (|z_1|^2+|z_2|^2+...+|z_k|^2)I_{n \\times n}$. Adams et al. in "The final case of the decoding delay problem for maximum rate complex orthogonal designs," IEEE Trans. Inf. Theory, vol. 56, no. 1, pp. 103-122, Jan. 2010, first proved the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, COD. Combining with the previous result that decoding delay should be an integer multiple of $\\binom{2m}{m-1}$, they solved the final case $n \\equiv 2 \\pmod 4$ of the decoding delay problem for maximum rate complex orthogonal designs. In this paper, we give another proof of the nonexistence of COD with parameter $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd. Our new proof is based on the uniqueness of $[\\binom{2m}{m-1}, 2m-1, \\binom{...

  20. Susceptibility of biallelic haplotype and genotype frequencies to genotyping error.

    Science.gov (United States)

    Moskvina, Valentina; Schmidt, Karl Michael

    2006-12-01

    With the availability of fast genotyping methods and genomic databases, the search for statistical association of single nucleotide polymorphisms with a complex trait has become an important methodology in medical genetics. However, even fairly rare errors occurring during the genotyping process can lead to spurious association results and decrease in statistical power. We develop a systematic approach to study how genotyping errors change the genotype distribution in a sample. The general M-marker case is reduced to that of a single-marker locus by recognizing the underlying tensor-product structure of the error matrix. Both method and general conclusions apply to the general error model; we give detailed results for allele-based errors of size depending both on the marker locus and the allele present. Multiple errors are treated in terms of the associated diffusion process on the space of genotype distributions. We find that certain genotype and haplotype distributions remain unchanged under genotyping errors, and that genotyping errors generally render the distribution more similar to the stable one. In case-control association studies, this will lead to loss of statistical power for nondifferential genotyping errors and increase in type I error for differential genotyping errors. Moreover, we show that allele-based genotyping errors do not disturb Hardy-Weinberg equilibrium in the genotype distribution. In this setting we also identify maximally affected distributions. As they correspond to situations with rare alleles and marker loci in high linkage disequilibrium, careful checking for genotyping errors is advisable when significant association based on such alleles/haplotypes is observed in association studies.

  1. Genotypic Tannin Levels in Populus tremula Impact the Way Nitrogen Enrichment Affects Growth and Allocation Responses for Some Traits and Not for Others.

    Directory of Open Access Journals (Sweden)

    Franziska Bandau

    Full Text Available Plant intraspecific variability has been proposed as a key mechanism by which plants adapt to environmental change. In boreal forests where nitrogen availability is strongly limited, nitrogen addition happens indirectly through atmospheric N deposition and directly through industrial forest fertilization. These anthropogenic inputs of N have numerous environmental consequences, including shifts in plant species composition and reductions in plant species diversity. However, we know less about how genetic differences within plant populations determine how species respond to eutrophication in boreal forests. According to plant defense theories, nitrogen addition will cause plants to shift carbon allocation more towards growth and less to chemical defense, potentially enhancing vulnerability to antagonists. Aspens are keystone species in boreal forests that produce condensed tannins to serve as chemical defense. We conducted an experiment using ten Populus tremula genotypes from the Swedish Aspen Collection that express extreme levels of baseline investment into foliar condensed tannins. We investigated whether investment into growth and phenolic defense compounds in young plants varied in response to two nitrogen addition levels, corresponding to atmospheric N deposition and industrial forest fertilization. Nitrogen addition generally caused growth to increase, and tannin levels to decrease; however, individualistic responses among genotypes were found for height growth, biomass of specific tissues, root:shoot ratios, and tissue lignin and N concentrations. A genotype's baseline ability to produce and store condensed tannins also influenced plant responses to N, although this effect was relatively minor. High-tannin genotypes tended to grow less biomass under low nitrogen levels and more at the highest fertilization level. Thus, the ability in aspen to produce foliar tannins is likely associated with a steeper reaction norm of growth responses

  2. Genotypic Tannin Levels in Populus tremula Impact the Way Nitrogen Enrichment Affects Growth and Allocation Responses for Some Traits and Not for Others.

    Science.gov (United States)

    Bandau, Franziska; Decker, Vicki Huizu Guo; Gundale, Michael J; Albrectsen, Benedicte Riber

    2015-01-01

    Plant intraspecific variability has been proposed as a key mechanism by which plants adapt to environmental change. In boreal forests where nitrogen availability is strongly limited, nitrogen addition happens indirectly through atmospheric N deposition and directly through industrial forest fertilization. These anthropogenic inputs of N have numerous environmental consequences, including shifts in plant species composition and reductions in plant species diversity. However, we know less about how genetic differences within plant populations determine how species respond to eutrophication in boreal forests. According to plant defense theories, nitrogen addition will cause plants to shift carbon allocation more towards growth and less to chemical defense, potentially enhancing vulnerability to antagonists. Aspens are keystone species in boreal forests that produce condensed tannins to serve as chemical defense. We conducted an experiment using ten Populus tremula genotypes from the Swedish Aspen Collection that express extreme levels of baseline investment into foliar condensed tannins. We investigated whether investment into growth and phenolic defense compounds in young plants varied in response to two nitrogen addition levels, corresponding to atmospheric N deposition and industrial forest fertilization. Nitrogen addition generally caused growth to increase, and tannin levels to decrease; however, individualistic responses among genotypes were found for height growth, biomass of specific tissues, root:shoot ratios, and tissue lignin and N concentrations. A genotype's baseline ability to produce and store condensed tannins also influenced plant responses to N, although this effect was relatively minor. High-tannin genotypes tended to grow less biomass under low nitrogen levels and more at the highest fertilization level. Thus, the ability in aspen to produce foliar tannins is likely associated with a steeper reaction norm of growth responses, which suggests a

  3. Genotyping-by-sequencing approach indicates geographic distance as the main factor affecting genetic structure and gene flow in Brazilian populations of Grapholita molesta (Lepidoptera, Tortricidae)

    OpenAIRE

    Silva-Brandão, Karina Lucas; Oscar Arnaldo Batista Neto E Silva; Brandão, Marcelo Mendes; Omoto, Celso; Sperling, Felix A. H.

    2015-01-01

    The oriental fruit moth Grapholita molesta is one of the major pests of stone and pome fruit species in Brazil. Here, we applied 1226 SNPs obtained by genotyping-by-sequencing to test whether host species associations or other factors such as geographic distance structured populations of this pest. Populations from the main areas of occurrence of G. molesta were sampled principally from peach and apple orchards. Three main clusters were recovered by neighbor-joining analysis, all defined by g...

  4. Genotypic Tannin Levels in Populus tremula Impact the Way Nitrogen Enrichment Affects Growth and Allocation Responses for Some Traits and Not for Others

    Science.gov (United States)

    Bandau, Franziska; Decker, Vicki Huizu Guo; Gundale, Michael J.; Albrectsen, Benedicte Riber

    2015-01-01

    Plant intraspecific variability has been proposed as a key mechanism by which plants adapt to environmental change. In boreal forests where nitrogen availability is strongly limited, nitrogen addition happens indirectly through atmospheric N deposition and directly through industrial forest fertilization. These anthropogenic inputs of N have numerous environmental consequences, including shifts in plant species composition and reductions in plant species diversity. However, we know less about how genetic differences within plant populations determine how species respond to eutrophication in boreal forests. According to plant defense theories, nitrogen addition will cause plants to shift carbon allocation more towards growth and less to chemical defense, potentially enhancing vulnerability to antagonists. Aspens are keystone species in boreal forests that produce condensed tannins to serve as chemical defense. We conducted an experiment using ten Populus tremula genotypes from the Swedish Aspen Collection that express extreme levels of baseline investment into foliar condensed tannins. We investigated whether investment into growth and phenolic defense compounds in young plants varied in response to two nitrogen addition levels, corresponding to atmospheric N deposition and industrial forest fertilization. Nitrogen addition generally caused growth to increase, and tannin levels to decrease; however, individualistic responses among genotypes were found for height growth, biomass of specific tissues, root:shoot ratios, and tissue lignin and N concentrations. A genotype’s baseline ability to produce and store condensed tannins also influenced plant responses to N, although this effect was relatively minor. High-tannin genotypes tended to grow less biomass under low nitrogen levels and more at the highest fertilization level. Thus, the ability in aspen to produce foliar tannins is likely associated with a steeper reaction norm of growth responses, which suggests a

  5. The conformation of acetylated virginiamycin M1 and virginiamycin M1 in explicit solvents.

    Science.gov (United States)

    Ng, Chai Ann; Zhao, Wen; Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2007-05-01

    The three-dimensional structure of acetylated virginiamycin M(1) (acetylated VM1) in chloroform and in a water/acetonitrile mixture (83:17 v/v) have been established through 2D high resolution NMR experiments and molecular dynamics modeling and the results compared with the conformation of the antibiotic VM1 in the same and other solvents. The results indicated that acetylation of the C-14 OH group of VM1 caused it to rotate about 90 degrees from the position it assumed in non-acetylated VM1. The conformation of both VM1 and acetylated VM1 appear to flatten in moving from a nonpolar to polar solvent. However, the acetylated form has a more hydrophobic nature. The acetylated VM1 in chloroform and in water/acetonitrile solution had a similar configuration to that of VM1 bound to 50S ribosomes and to the Vat(D) active sites as previously determined by X-ray crystallography. Docking studies of VM1 to the 50S ribosomal binding site and the Vat(D) gave conformations very similar to those derived from X-ray crystallographic studies. The docking studies with acetylated VM1 suggested the possibility of a hydrogen bond from the acetyl carbonyl group oxygen of acetylated VM1 to the 2' hydroxyl group of ribose of adenosine 2538 at the ribosomal VM1 binding site. No hydrogen bonds between acetylated VM1 and the Vat(D) active sites were found; the loss of this binding interaction partly accounts for the release of the product from the active site.

  6. Genotyping-by-sequencing approach indicates geographic distance as the main factor affecting genetic structure and gene flow in Brazilian populations of Grapholita molesta (Lepidoptera, Tortricidae).

    Science.gov (United States)

    Silva-Brandão, Karina Lucas; Silva, Oscar Arnaldo Batista Neto E; Brandão, Marcelo Mendes; Omoto, Celso; Sperling, Felix A H

    2015-06-01

    The oriental fruit moth Grapholita molesta is one of the major pests of stone and pome fruit species in Brazil. Here, we applied 1226 SNPs obtained by genotyping-by-sequencing to test whether host species associations or other factors such as geographic distance structured populations of this pest. Populations from the main areas of occurrence of G. molesta were sampled principally from peach and apple orchards. Three main clusters were recovered by neighbor-joining analysis, all defined by geographic proximity between sampling localities. Overall genetic structure inferred by a nonhierarchical amova resulted in a significant ΦST value = 0.19109. Here, we demonstrate for the first time that SNPs gathered by genotyping-by-sequencing can be used to infer genetic structure of a pest insect in Brazil; moreover, our results indicate that those markers are very informative even over a restricted geographic scale. We also demonstrate that host plant association has little effect on genetic structure among Brazilian populations of G. molesta; on the other hand, reduced gene flow promoted by geographic isolation has a stronger impact on population differentiation.

  7. Qualification Lab Testing on M1 Abrams Engine Oil Filters

    Science.gov (United States)

    2016-11-01

    UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K. Rutta U.S...the originator. UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K...TITLE AND SUBTITLE Qualification Lab Testing on M1 Abrams Engine Oil Filter 5a. CONTRACT NUMBER W56HZV-15-C-0030 5b. GRANT NUMBER 5c. PROGRAM

  8. Develop Efficient Leak Proof M1 Abrams Plenum Seal

    Science.gov (United States)

    2014-05-07

    UNCLASSIFIED UNCLASSIFIED ER-GLSV11389-001.docx Develop Efficient Leak Proof M1 Abrams Plenum Seal SBIR Phase I: Topic A13-061...Leak Proof M1 Abrams Plenum Seal Christian Muehfeld Steve Pennala Great Lakes Sound & Vibration, Inc. 47140 North Main Street Houghton, MI 49931 ER...061. The purpose of this report is to show the feasibility of developing an efficient, leak proof plenum seal for the M1 Abrams . It also shows the

  9. The seed's protein and oil content, fatty acid composition, and growing cycle length of a single genotype of chia (Salvia hispanica L.) as affected by environmental factors.

    Science.gov (United States)

    Ayerza, Ricardo

    2009-01-01

    As a botanical source, variability in chia seed composition could be expected between growing locations, and between years within a location, due to genotype and environment effects as well genetic x environment's interactions. The objective of the present study was to determine the location effect on the growing cycle length, and seed's protein content, lipid content, and fatty acid profiles, of a single chia genotype. Seeds of chia genotype Tzotzol grown on eight sites in five different ecosystems were tested. One site was in Argentina, in the Semi-Arid Chaco ecosystem (T(5)); one was in Bolivia, in the Sub-Humid Chaco ecosystem (T(4)); and six in Ecuador, one in the Coastal Desert (T(3)), two on the Tropical Rain Forest (T(2)), and three in the Inter-Andean Dry Valley ecosystem (T(1)). Seeds from plants grown in T(4) and in T(3) contained significantly (P <0.05) more protein percentage than did seeds from the other three ecosystems. No significant (P <0.05) differences in protein content were found between T(3) and T(4), and between T(1), T(2), and T(5). Seeds from T(1) and T(5) ecosystems, with 33.5 and 32.2%, respectively, were the numerically highest oil content producers, but their results were only significantly (P <0.05) higher when compared with the T(2) seeds. Significant (P <0.05) differences in palmitic, stearic, oleic, linoleic and alpha-linolenic fatty acids between oils from seeds grown in different ecosystems were detected, however. Oil of seeds grown in the T(3) ecosystem had the palmitic, stearic and oleic fatty acids' highest contents. Palmitic and oleic fatty acid levels were significantly (P <0.05) higher when were compared to that of seeds grown in the T(1) ecosystem, and stearic when was compared to that of seeds grown in the T(5) ecosystem; omega-6 linoleic fatty acid content was significantly (P <0.05) lower in oils of seeds produced in T(1), and T(2) than in those produced in T(3), T(4), and T(5) ecosystems; omega-3 alpha-linolenic fatty

  10. Glutathione s-transferase M1 and T1 genetic polymorphisms in Iranian patients with glaucoma

    Directory of Open Access Journals (Sweden)

    Fatemeh Kazemi Safa

    2014-05-01

    Full Text Available Objective(s:Glaucoma is the second leading cause of blindness and it is related to oxidative stress based on numerous studies. Glutathione S-transferases (GSTs are members of multigenic family, which have important role in cells as an antioxidant. In the present study, we examined the polymorphism of GSTT1 and GSTM1 deletion genotypes (T0M1, T1M0, and T0M0 in 100 Glaucoma patients (41with primary open angle glaucoma (PCAG, and 59 with primary closed angle glaucoma (POAG compared to 100 healthy subjects. Materials and Methods: GSTM1and GSTT1 polymorphisms were determined by multiplex polymerase chain reaction. Results: GSTM1 and GSTT1 null deletions genotypes were determined in 22 (53.7% and 7 (17.1% patients with PCAG and 34 (34% and 15 (15% in healthy subjects[VAIO1] . Comparison between patients and healthy subjects regarding GSTM1 and GSTT1 genotypes revealed increase of GSTM1 null deletions genotypes in patients with PCAG (P=0.03. Conclusion: It was concluded that the increased frequencies of GSTM1 null in patients with PCAG could be a risk factor for incidence of PCAG in the Iranian population.  

  11. Genomic Characterization of Campylobacter jejuni strain M1

    DEFF Research Database (Denmark)

    Friis, Carsten; Wassenaar, Gertrude Maria; Javed, Muhammad A.

    2010-01-01

    publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core...

  12. FoxM1 Regulates Mammary Luminal Cell Fate

    Directory of Open Access Journals (Sweden)

    Janai R. Carr

    2012-06-01

    Full Text Available Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.

  13. Maize Genotype and Food Matrix Affect the Provitamin A Carotenoid Bioefficacy from Staple and Carrot-fortified Feeds in Mongolian Gerbils (Meriones unguiculatus)

    Science.gov (United States)

    Schmaelzle, Samantha; Gannon, Bryan; Crawford, Serra; Arscott, Sara A.; Goltz, Shellen; Palacios-Rojas, Natalia; Pixley, Kevin V.; Simon, Philipp W.; Tanumihardjo, Sherry A.

    2014-01-01

    Biofortification to increase provitamin A carotenoids is an agronomic approach to alleviate vitamin A deficiency. Two studies compared biofortified foods using in vitro and in vivo methods. Study 1 screened maize genotypes (n = 44) using in vitro analysis, which demonstrated decreasing micellarization with increasing provitamin A. Thereafter, seven 50% biofortified maize feeds that hypothesized a one-to-one equivalency between β-cryptoxanthin and β-carotene were fed to Mongolian gerbils. Total liver retinol differed among the maize groups (P = 0.0043). Study 2 assessed provitamin A bioefficacy from 0.5% high-carotene carrots added to 60% staple-food feeds, followed by in vitro screening. Liver retinol was highest in the potato and banana groups, maize group retinol did not differ from baseline, and all treatments differed from control (P < 0.0001). In conclusion, β-cryptoxanthin and β-carotene have similar bioefficacy; meal matrix effects influence provitamin A absorption from carrot; and in vitro micellarization does not predict bioefficacy. PMID:24341827

  14. Genotype and fetal size affect maternal-fetal amino acid status and fetal endocrinology in Large White × Landrace and Meishan pigs.

    Science.gov (United States)

    Ashworth, Cheryl J; Nwagwu, Margaret O; McArdle, Harry J

    2013-01-01

    This study compared maternal plasma amino acid concentrations, placental protein secretion in vitro and fetal body composition and plasma amino acid and hormone concentrations in feto-placental units from the smallest and a normally-sized fetus carried by Large White × Landrace or Meishan gilts on Day 100 of pregnancy. Compared with Large White × Landrace, Meishan placental tissue secreted more protein and Meishan fetuses contained relatively more fat and protein, but less moisture. Fetal plasma concentrations of insulin, triiodothryonine, thyroxine and insulin-like growth factor (IGF)-II were higher in Meishan than Large White × Landrace fetuses. In both breeds, fetal cortisol concentrations were inversely related to fetal size, whereas concentrations of IGF-I were higher in average-sized fetuses. Concentrations of 10 amino acids were higher in Large White × Landrace than Meishan gilts, while glutamine concentrations were higher in Meishan gilts. Concentrations of alanine, aspartic acid, glutamic acid and threonine were higher in Meishan than Large White × Landrace fetuses. Average-sized fetuses had higher concentrations of asparagine, leucine, lysine, phenylalanine, threonine, tyrosine and valine than the smallest fetus. This study revealed novel genotype and fetal size differences in porcine maternal-fetal amino acid status and fetal hormone and metabolite concentrations.

  15. On (2m + 1)-variable symmetric Boolean functions with submaximum algebraic immunity 2m-1

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    All (2m +1)-variable symmetric Boolean functions with submaximal algebraic immunity 2m-1 are described and constructed. The total number of such Boolean functions is 32 ·22m-3 +3m-2 · 24 - 2 for m≥2.

  16. Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

    Science.gov (United States)

    He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

    2015-01-01

    Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio.

  17. Intergenerational Instability of the CAG Repeat of the Gene for Machado-Joseph Disease (MJD1) is Affected by the Genotype of the Normal Chromosome

    OpenAIRE

    五十嵐, 修一; Igarashi, Shuichi

    1997-01-01

    Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at 14q32.1. To identify elements affecting the intergenerational instability of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the 3' end of the CAG repeat affects the intergenerational instability of the CAG repeat. The [expanded (CAG) n-CGG]/[normal (CAG) n-GGG] haplotypes were found to result in significantly greater instability...

  18. Diverse Effects on M1 Signaling and Adverse Effect Liability within a Series of M1 Ago-PAMs.

    Science.gov (United States)

    Rook, Jerri M; Abe, Masahito; Cho, Hyekyung P; Nance, Kellie D; Luscombe, Vincent B; Adams, Jeffrey J; Dickerson, Jonathan W; Remke, Daniel H; Garcia-Barrantes, Pedro M; Engers, Darren W; Engers, Julie L; Chang, Sichen; Foster, Jarrett J; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Conn, P Jeffrey; Lindsley, Craig W

    2017-01-10

    Both historical clinical and recent preclinical data suggest that the M1 muscarinic acetylcholine receptor is an exciting target for the treatment of Alzheimer's disease and the cognitive and negative symptom clusters in schizophrenia; however, early drug discovery efforts targeting the orthosteric binding site have failed to afford selective M1 activation. Efforts then shifted to focus on selective activation of M1 via either allosteric agonists or positive allosteric modulators (PAMs). While M1 PAMs have robust efficacy in rodent models, some chemotypes can induce cholinergic adverse effects (AEs) that could limit their clinical utility. Here, we report studies aimed at understanding the subtle structural and pharmacological nuances that differentiate efficacy from adverse effect liability within an indole-based series of M1 ago-PAMs. Our data demonstrate that closely related M1 PAMs can display striking differences in their in vivo activities, especially their propensities to induce adverse effects. We report the discovery of a novel PAM in this series that is devoid of observable adverse effect liability. Interestingly, the molecular pharmacology profile of this novel PAM is similar to that of a representative M1 PAM that induces severe AEs. For instance, both compounds are potent ago-PAMs that demonstrate significant interaction with the orthosteric site (either bitopic or negative cooperativity). However, there are subtle differences in efficacies of the compounds at potentiating M1 responses, agonist potencies, and abilities to induce receptor internalization. While these differences may contribute to the differential in vivo profiles of these compounds, the in vitro differences are relatively subtle and highlight the complexities of allosteric modulators and the need to focus on in vivo phenotypic screening to identify safe and effective M1 PAMs.

  19. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    Science.gov (United States)

    Kasthurinaidu, Senthilkumar Pitchalu; Ramasamy, Thirumurugan; Ayyavoo, Jayachitra; Dave, Dhvani Kirtikumar; Adroja, Divya Anantray

    2015-01-01

    Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME). Among the XMEs, glutathione-S-transferases (GST) gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs). Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs). The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions) and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  20. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    Directory of Open Access Journals (Sweden)

    Senthilkumar Pitchalu Kasthurinaidu

    Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  1. Personality and serotonin transporter genotype interact with social context to affect immunity and viral set-point in simian immunodeficiency virus disease

    OpenAIRE

    2007-01-01

    From the beginning of the AIDS epidemic, stress has been a suspected contributor to the wide variation seen in disease progression, and some evidence supports this idea. Not all individuals respond to a stressor in the same way, however, and little is known about the biological mechanisms by which variations in individuals’ responses to their environment affect disease-relevant immunologic processes. Using the simian immunodeficiency virus/rhesus macaque model of AIDS, we explored how persona...

  2. Broad analgesic activity of a novel, selective M1 agonist.

    Science.gov (United States)

    Wood, Michael W; Martino, Giovanni; Coupal, Martin; Lindberg, Mattias; Schroeder, Patricia; Santhakumar, Vijayaratnam; Valiquette, Manon; Sandin, Johan; Widzowski, Daniel; Laird, Jennifer

    2017-09-01

    Although the muscarinic receptor family has long been a source of potentially compelling targets for small molecule drug discovery, it was difficult to achieve agonist selectivity within the family. A new class of M1 muscarinic agonists has emerged, and these compounds have been characterized as agonists that activate the receptor at an allosteric site. Members of this class of M1 agonists have been shown to be selective across the muscarinic receptors. However, upon introduction of a novel pharmacologic mechanism, it is prudent to ensure that no new off-target activities have arisen, particularly within the context of in vivo experiments. Reported here, is the in vitro and in vivo characterization of a novel M1 agonist tool compound, PPBI, and demonstrations that the primary biological effects of PPBI are mediated through M1. PPBI reverses d-amphetamine locomotor activity, but fails to do so in transgenic mice that do not express M1. PPBI also reverses a natural deficit in a rat cognition model at a level of exposure which also activates cortical circuitry. Most notably, PPBI is analgesic in a variety of rat and mouse models and the analgesic effect of PPBI is reversed by an M1-preferring antagonist and an M1-selective toxin. Finally, the pharmacokinetic/pharmacodynamic measures of PPBI are compared across multiple endpoints which highlights that activity in models of psychosis and pain require higher exposures than that required in the cognition model. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. The signature of scrapie: differences in the PrP genotype profile of scrapie-affected and scrapie-free UK sheep flocks.

    OpenAIRE

    Baylis, M.; Houston, Fiona; Goldmann, W.; Hunter, N.; McLean, A.R.

    2000-01-01

    The amino-acid sequence of the PrP protein plays an important role in determining whether sheep are susceptible to scrapie. Although the genetics of scrapie susceptibility are now well understood, there have been few studies of the PrP gene at the population level, especially in commercially farmed sheep. Here we describe the PrP genetic profiles of the breeding stock of four UK sheep flocks, comprising nearly 650 animals in total. Two flocks had been scrapie affected for about eight years an...

  4. M1.3--a small scaffold for DNA origami .

    Science.gov (United States)

    Said, Hassan; Schüller, Verena J; Eber, Fabian J; Wege, Christina; Liedl, Tim; Richert, Clemens

    2013-01-07

    The DNA origami method produces programmable nanoscale objects that form when one long scaffold strand hybridizes to numerous oligonucleotide staple strands. One scaffold strand is dominating the field: M13mp18, a bacteriophage-derived vector 7249 nucleotides in length. The full-length M13 is typically folded by using over 200 staple oligonucleotides. Here we report the convenient preparation of a 704 nt fragment dubbed "M1.3" as a linear or cyclic scaffold and the assembly of small origami structures with just 15-24 staple strands. A typical M1.3 origami is large enough to be visualized by TEM, but small enough to show a cooperativity in its assembly and thermal denaturation that is reminiscent of oligonucleotide duplexes. Due to its medium size, M1.3 origami with globally modified staples is affordable. As a proof of principle, two origami structures with globally 5'-capped staples were prepared and were shown to give higher UV-melting points than the corresponding assembly with unmodified DNA. M1.3 has the size of a gene, not a genome, and may function as a model for gene-based nanostructures. Small origami with M1.3 as a scaffold may serve as a workbench for chemical, physical, and biological experiments.

  5. Surface properties of new virginiamycin M(1) derivatives.

    Science.gov (United States)

    Nott, Katherine; Paquot, Michel; Dufour, Samuel; Eeman, Marc; Deleu, Magali

    2009-03-01

    Three kinds of derivatives of the M(1) factor of virginiamycin have been synthesised: esters with long chain fatty acids, oximes with modified polar amino acids and bis-derivatives with both the ester and oxime function. The study of the surface tension time dependence of M(1) and its derivatives has shown that it is necessary to enhance simultaneously the hydrophobicity and the hydrophilicity of M(1) to render M(1) surface-active. A structure/function relationship study of the surface-active bis-derivatives has shown that enhancing the hydrophobicity of the molecule led to slower adsorption kinetics, higher stability of the monolayers formed and a better capacity to penetrate a membrane model. The repulsive electrostatic forces due to the presence of charges on the amino acids linked to M(1) lead to higher surface tensions, a greater molecular area at the interface and lower penetration into a membrane model. This study has demonstrated that modifying systematically the hydrophobicity and hydrophilicity of a non surface-active molecule allows the production of surface-active derivatives.

  6. Genomic characterization of Campylobacter jejuni strain M1.

    Directory of Open Access Journals (Sweden)

    Carsten Friis

    Full Text Available Campylobacter jejuni strain M1 (laboratory designation 99/308 is a rarely documented case of direct transmission of C. jejuni from chicken to a person, resulting in enteritis. We have sequenced the genome of C. jejuni strain M1, and compared this to 12 other C. jejuni sequenced genomes currently publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core genome comprised 1,295 gene families, or about two-thirds of the gene content of the average of the sequenced C. jejuni genomes. Various comparison and visualization tools were applied to the 13 C. jejuni genome sequences, including a species pan- and core genome plot, a BLAST Matrix and a BLAST Atlas. Trees based on 16S rRNA sequences and on the total gene families in each genome are presented. The findings are discussed in the background of the proven virulence potential of M1.

  7. Investigation of aflatoxin M1 degradation in milk

    Directory of Open Access Journals (Sweden)

    Smajlović Ahmed

    2012-01-01

    Full Text Available Aflatoxin M1 is a highly toxic 4-hydroxylated metabolite of aflatoxins B1 and B2. It is one of the most potent hepatocarcinogens, mutagens, teratogens and immunosuppressors. Feed is often contaminated with aflatoxigenic moulds and aflatoxins with a high possibility of contaminating milk and dairy products with aflatoxin M1. Samples of artificially contaminated milk were exposed to the effects of physical conditions (temperature of -18oC and for microwaves in a microwave oven, time (during the period from 1 to 12 months and a combination of the above mentioned conditions. Following this, levels of aflatoxin M1 degradation were established by using the ELISA method. An insignificant decrease in concentration of toxin was observed which indicates that a temperature of -18°C does not significantly influence the concentration of aflatoxin M1 in the artificially contaminated milk. At the same time, treatment of milk with microwaves in a microwave oven showed an insignificant influence on the percentage of aflatoxin M1 absorbance.

  8. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  9. Theory of the M = 1 Kink Mode in Toroidal Plasma

    NARCIS (Netherlands)

    de Blank, H. J.; Schep, T. J.

    1991-01-01

    The energy principle of ideal magnetohydrodynamics (MHD) is used to study the ideal MHD stability of the m = 1 internal kink mode in a toroidal plasma. The equilibrium configurations that are considered allow for a broad region where the safety factor q is close to unity. This region may extend to t

  10. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  11. Reproductive efficiency and metabolism of female broiler breeders as affected by genotype, feed allocation, and age at photostimulation. 3. Reproductive efficiency.

    Science.gov (United States)

    Zuidhof, M J; Renema, R A; Robinson, F E

    2007-10-01

    A 3 x 4 x 2 factorial trial was performed to test the effect of 3 broiler breeder strains, 4 target BW profiles, and 2 photostimulation ages on egg and chick production. Hubbard Hi-Y, Ross 508, and Ross 708 pullets were reared on BW profiles that separated at 4 wk and converged at 32 wk: standard (approximate mean target BW profile of the 3 strains used), low (12-wk BW target = 25% lower than standard followed by rapid gain to 32 wk), moderate (12-wk BW target = 150% of standard followed by lower rate of gain to 32 wk), and high (12-wk BW target = 200% of standard followed by minimal growth to 32 wk). Birds were photostimulated at 18 (18WK) or 22 wk (22WK). Twelve birds per interaction (n = 288) were individually caged at 17 wk and monitored for egg and chick production to 58 wk of age. The low BW profile delayed onset of lay, particularly in 18WK hens. Low and standard birds had a greater initial egg weight than moderate birds. The 18WK photostimulation age resulted in production of 31 small eggs (birds. A settable (52 g) egg weight was reached earliest by standard birds (187 d of age). Average prime sequence length was reduced by 7.0 eggs in moderate and high birds compared with other profiles. The 18WK hens laid 9 more eggs (174) than 22WK birds, with no effect on unsettable eggs. The 22WK birds laid 7 more settable eggs due to increased early egg size. Total egg output was similar among BW profile treatments, although Ross 708-high hens under-performed compared with the other 708 profiles. The Ross 508-high birds laid the same number of eggs as Ross 508-standard birds (mean = 178.7). Feeding profiles affected egg production traits differently among strains. Feed intake had more effect on egg size and early production traits than BW profile or BW.

  12. Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning

    Science.gov (United States)

    Chan, Wilson; Singh, Sanmeet; Keshav, Taj; Dewan, Ramita; Eberly, Christian; Maurer, Robert; Nunez-Parra, Alexia; Araneda, Ricardo C.

    2017-01-01

    The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1−/− and the M1/M3−/− knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing. PMID:28210219

  13. Genotypic Variation for Salinity Tolerance in Sorghum (Sorghum bicolor (L. Moench Genotypes at Early Growth Stages

    Directory of Open Access Journals (Sweden)

    Tigabu, Endalew

    2013-04-01

    Full Text Available Sorghum (Sorghum bicolor L. Moench is the fifth most economically important crop among cereals in the world. Salinity is an abiotic factor which reduces productivity of sorghum. Exploiting genetic variability to identify salt tolerant genotype is one of the strategies used to overcome salinity. Pot experiment was carried out to evaluate the genetic variation of eleven sorghum genotypes for NaCl salinity response at germination and early seedling stages. The experimental treatments were five NaCl salinity levels (0, 2, 4, 8, and 16 dS m-1 and eleven sorghum genotypes (Gambella1107, Melkam, S-35, ESH-2, Gobye, 97MW6130, Meko, 76T1#23, ICSV-111, Abshir and Teshale. The experimental design was completely randomized design with three replicates.Data was analyzed using SAS (version 9.0 statistical software and means were separated by LSD. Germination rate, final germination percentage, seedling shoot length and seedling root length were measured. The ANOVA for treatments, genotypes and their interaction was found to be highly significant (p<0.001 with regard to all parameters. Genotypes Meko, Gambella1107, ICSV-111 and Melkam were found salt tolerant during germination and seedling growth stages. However, genotypes ESH-2 and Gobye were salt sensitive during both stages. The rest sorghum genotypes were intermediate in their salt tolerance. The study affirmed the presence of wide genotypic variation among the sorghum genotypes for NaCl salt tolerance.

  14. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Hoblit, S. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.]|[Univ. of Virginia, Charlottesville, VA (United States). Dept. of Physics; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-10-01

    New high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. The E2/M1 mixing ratio for the n {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  15. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Sandorfi, A.M. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-08-01

    The properties of the transition from the nucleon to the {Delta}(1232) serve as a benchmark for models of nucleon structure. To first order, N {r_arrow} {Delta} photo-excitation is dominated by a simple M1 quark spin-flip transition. At higher order, small L = 2 components in the N and {Delta} wavefunctions allow this excitation to proceed via an electric quadrupole transition. Since Nucleon models differ greatly on the mechanisms used to generate these L = 2 components,, the ratio of E2/M1 transitions (EMR) provides a sensitive test for structure models. Here, new high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. Compton scattering has provided two important new constraints on the photo-pion amplitude. The E2/M1 mixing ratio for the N {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  16. Identification of Mislabeled Samples and Sample Mix-ups in Genotype Data using Barcode Genotypes

    DEFF Research Database (Denmark)

    Have, Christian Theil; Appel, Emil Vincent Rosenbaum; Grarup, Niels

    2014-01-01

    barcode genotypes. To detect mislabeled samples we calculate the probability that the discordance between genotypes in the data and in the independent genotypes can be attributed to random (non-mislabeling) genotyping errors. To identify mix-ups we calculate the probability of identifying the set...... of identical genotypes between sample x and sample y by chance. Based on this we calculate a mix-up confidence score with penalization for introducing mismatches in the proposed new label and adjustment for independency among the genotypes. This confidence score is used to identify probable mix-ups.......Abstract—Undetected mislabeled samples may affect the results of genotype studies, particular when rare genetic variants are investigated. Mislabeled samples are often not detected during quality control and if they are detected, they are normally discarded due to a lack of a reliable method...

  17. Effect of the radial plasma nonuniformity on the propagation of guided m = + 1 and m = - 1 modes in helicon discharges

    Science.gov (United States)

    Aliev, Yu. M.; Krämer, M.

    2016-10-01

    Theoretical as well as numerical analyses of the full set of Maxwell's equations is carried out to study non-axisymmetric ( m ≠ 0 ) guided modes in radially nonuniform helicon (HE) discharges. Unlike the axisymmetric (m = 0) modes, these modes reveal a non-reciprocal behavior with respect to the azimuthal direction. We develop the conditions for propagation and non-propagation of the various modes in the helicon parameter range, thereby focussing on the important role of the radial density gradient. Three types of modes occurring in different parameter ranges are described, i.e., the helicon (HE) mode, the electrostatic (ES) or Trivelpiece-Gould mode, and the locally coupled (LC) mode that is characterized by mode coupling (MC) in a certain region of the plasma density profile. In contrast to m = + 1 modes, the parameter range of m = - 1 modes is much more restricted as rather high densities are needed for the propagation of the helicon and LC modes. An important issue of the investigations is the rf power coupling and absorption via the various modes. Computations based on a simple antenna-plasma model show that the axial wavenumber of the antenna determines decisively which type of mode is excited. In case of LC mode excitation, the dominant role of the MC layer for the absorption is demonstrated. Finally, the rf power coupling to helicon modes is studied. The density limit for m = - 1 helicon mode propagation and the narrow magnetic field profiles of these modes are the main reasons why the rf power absorption in helicon discharges occurs via m = + 1 helicon modes.

  18. Electrochemical immunochip sensor for aflatoxin M1 detection.

    Science.gov (United States)

    Parker, Charlie O; Lanyon, Yvonne H; Manning, Mary; Arrigan, Damien W M; Tothill, Ibtisam E

    2009-07-01

    An investigation into the fabrication, electrochemical characterization, and development of a microelectrode array (MEA) immunosensor for aflatoxin M(1) is presented in this paper. Gold MEAs (consisting of 35 microsquare electrodes with 20 microm x 20 microm dimensions and edge-to-edge spacing of 200 microm) together with on-chip reference and counter electrodes were fabricated using standard photolithographic methods. The MEAs were then characterized by cyclic voltammetry, and the behavior of the on-chip electrodes were evaluated. The microarray sensors were assessed for their applicability to the development of an immunosensor for the analysis of aflatoxin M(1) directly in milk samples. Following the sensor surface silanization, antibodies were immobilized by cross-linking with 1,4-phenylene diisothiocyanate (PDITC). Surface characterization was conducted by electrochemistry, fluorescence microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). A competitive enzyme linked immunosorbent assay (ELISA) assay format was developed on the microarray electrode surface using the 3,3,5',5'-tetramethylbenzidine dihyrochloride (TMB)/H(2)O(2) electrochemical detection scheme with horseradish peroxidase (HRP) as the enzyme label. The performance of the assay and the microarray sensor were characterized in pure buffer conditions before applying to the milk samples. With the use of this approach, the detection limit for aflatoxin M(1) in milk was estimated to be 8 ng L(-1), with a dynamic detection range of 10-100 ng L(-1), which meets present legislative limits of 50 ng L(-1). The milk interference with the sensor surface was also found to be minimal. These devices show high potential for development of a range of new applications which have previously only been detected using elaborate instrumentation.

  19. A review of aflatoxin M1 in liquid milk

    OpenAIRE

    2015-01-01

    Mycotoxins continue to pose a health concern via human exposure to contaminated food. Aflatoxin M1 (AFM1), the hydroxylated metabolite of aflatoxin B1 (AFB1), may be found in the milk of dairy cattle and other mammals. In humans, AFM1 is excreted through the feces, urine, and in the case of lactating mothers, also in breast milk after consumption of aflatoxin contaminated food. Concentration of AFM1 in milk is a function of several factors, namely: animal type, milking day, milk yield, season...

  20. PEMBUATAN PROGRAM INTERFACE UNTUK PENGONTROLAN RV-M1

    Directory of Open Access Journals (Sweden)

    Endra Endra

    2007-10-01

    Full Text Available Article explores the making of interface of RV-M1 hand robot control that replaced the cosiprog program,a program that is able to help student in Mecatronica-1 Practice, and able to control the hand robot by localnetwork by two user or more. The used methods were literature study, and field study, that is design method. Theresearch result are control of hand robot on X,Y,Z axis and point to point, the use of local network to control thehand robot, save certain position, and use several user to control the robot.Keywords: interface program, robot, local network

  1. Effects on Variations in M1 Generation of Durum Wheat (T. durum Thell by Induced Mutagen

    Directory of Open Access Journals (Sweden)

    O. Bilgin

    2005-01-01

    Full Text Available In this research conducted ın Department of Field Crops, Tekirdağ Agricultural Faculty, TrakyaUniversity, the effect of six different gamma ray doses on plant growth in M1 generations derived from twodurum wheat cultivars was investigated.In the experiment, 10 plants in each pot (17 x 40 cm containing 5 kgsoil were grown with three replicates. Total 30 plants for each treatment were used. In M1 generation, numberof leaves, number of roots, seedling height, seedling weight, leaf weight and germination rate were determined.Application of 100-200 gray gamma ray doses did not have any inhibitory effect on investigated characters inseedling growth of M1 generation. On the other hand, 400-500 gray doses significantly inhibited the plantgrowth. 100-200 gray doses did not affect the seed germination rate whereas germination rate decreased with400-500 gray gamma ray applications. At 600 gray dose, only one seed remained viably, rest of them could notsurvive. It was generally observed the highest variations at 300-400 gray gamma doses in M1 plants.

  2. E1 and M1 strength functions at low energy

    Directory of Open Access Journals (Sweden)

    Schwengner Ronald

    2017-01-01

    Full Text Available We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  3. Evaluation of different glycoforms of honeybee venom major allergen phospholipase A2 (Api m 1) produced in insect cells

    DEFF Research Database (Denmark)

    Blank, Simon; Seismann, Henning; Plum, Melanie;

    2011-01-01

    Allergic reactions to hymenoptera stings are one of the major reasons for IgE-mediated anaphylaxis. However, proper diagnosis using venom extracts is severely affected by molecular cross-reactivity. In this study recombinant honeybee venom major allergen phospholipase A2 (Api m 1) was produced......-derived recombinant Api m 1 with defined CCD phenotypes might provide further insights into hymenoptera venom IgE reactivities and contribute to an improved diagnosis of hymenoptera venom allergy....

  4. Presence of moulds and aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Janković Vesna V.

    2009-01-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk or dairy products as a direct result of the cattle's ingestion of feed contaminated with aflatoxin B1 (AFB1. This study comprises mycological and mycotoxicological investigations of 23 milk samples (raw, infant food, pasteurized, whey and yoghurt. The mycological testing showed dominant presence of genus Geotrichum. G. candidum was found in 9 samples, with the highest contamination in the raw milk samples. The contamination level of AM1 is defined by using direct competitive enzyme- -linked immunosorbent assay (ELISA. AFM1 was found in 9 samples. AFM1 levels were lower than the recommended limits. However, as AFM1 is considered a probable human carcinogen (2B type, it is necessary to achieve a low level of AFM1 in milk. Therefore, cows' feed samples from various cowsheds are supposed to be evaluated routinely for aflatoxin, and kept away from fungal contamination as much as possible.

  5. Aflatoxin M1 Contamination in Ice-Cream

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-06-01

    Full Text Available Aflatoxin M1 (AFM1 is the hydroxylated metabolite of aflatoxin B1 (AFB1 that it can be found in milk and dairy products. In this study, ELISA (Enzyme Linked Immunosorbent Assay technique was used for detection of AFM1 in ice-cream in Guilan province (Northern Iran. A total of 90 ice-cream samples was randomly obtained from different supermarkets. In 62 of the 90 ice-cream samples examined (68.88%, the presence of AFM1 was detected in concentrations between 8.4 -147.7 ng/l. The mean level of AFM1 in positive samples was 40.36 ng/l. AFM1 levels in 11 samples (12.22% were higher than the maximum tolerance limit (50 ng/l accepted by ISIRI, European Community and Codex Alimentarius.

  6. [The BION-M1 project: overview and first results].

    Science.gov (United States)

    Sychev, V N; Ilyin, E A; Yarmanova, E N; Rakov, D V; Ushakov, I B; Kirilin, A N; Orlov, O I; Grigoriev, A I

    2014-01-01

    Biosatellite BION-M1 was launched on April 19 and landed on May 19, 2013. The mission program was largely a continuation of the earlier flown 11 BION projects, FOTON-M2 and FOTON-M3. The biosatellite was inhabited by a great variety of living organisms used for experiments and studies in gravitational physiology, gravitational biology, biotechnology, astrobiology and radiation biology, dosimetry and spectrometry. This was the first time in the history of national biology and physiology when male mice C57bl/6 were chosen for a long-term space experiment focused upon molecular biology investigations. Unfortunately, because of technical failures during the flight a part of the animals were lost. However, the major objectives were attained through reconsideration of biomaterial division among investigators and completion of virtually the total scope of investigations.

  7. Genotype adaptability and stability

    Directory of Open Access Journals (Sweden)

    Dimitrijević Miodrag

    2000-01-01

    Full Text Available One of the primary concerns in breeding programs is a small genotype reaction to environmental factor variation for better usage of yield genetic potential. Particularly if one takes in consideration that yield could van greatly because of more and more variable meteorological conditions. Studies conducted to observe genotype and environmental relations relay on numerous mathematical models, but genotype behavior in various ecological conditions is not, still, precisely defined Major sources of variation influencing genotype behavior in different environments are genotype/environment interaction, genetic background and environmental conditions. These factors could play an important role in establishing growth regions for maximal realization of genotype genetic potential, as well as in selection of genotypes having better response to complex requirements of particular growth region. Stability, the genotype ability to perform high, uniform yield no meter of different environmental conditions, and adaptability, genotype ability to give uniform yield in a different environmental conditions, are two common terms used to define genotype reaction in a consequence of environmental changes. Most of the models dealing with stability and adaptability are based on variation sources appearing under the influence of treatment, multivariate effects and residue. No meter which statistical model is used for GE interaction estimation, there is an opinion that no solid proof for the existence of stable genotypes obtained in breeding programs, which make some space for further investigations. There are still questions to answer dealing with definitions, sources of variation, usage value of existent models and interpretation of the results. .

  8. Formation of Polyhydroxyalkanoate Blends by Pseudomonas pseudoalcaligenes M1-2 from Various Carbon Sources

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Pseudomonas pseudoalcaligenes strain M1-2 isolated from oil-contaminated soil collected from an oilfield in northern China was found to be able to synthesize a blend of polyhydroxyalkanoates (PHAs) containing monomers of 3-hydroxybutyrate (C4), 3-hydroxyvalerate (C5), 3-hydroxyheptanoate (C7), 3-hydroxyoctanoate (C8), 3-hydroxynonanoate (C9), 3-hydroxydecanoate (C10) and 3-hydroxydodecanoate (C12) from various carbon sources.The hydroxyalkanoate (HA) monomer composition varied both quantitatively and qualitatively, depending on the carbon sources used.The presence of octanoate in substrates of myristic acid or tridecanoate promoted the synthesis of HB monomer in the blend.Concentration of octanoate was also found to significantly affect the PHB content in the blend.A PHA biosynthesis pathway in Pseudomonas pseudoalcaligens M1-2 was proposed.

  9. Lanthanum Affects Bell Pepper Seedling Quality Depending on the Genotype and Time of Exposure by Differentially Modifying Plant Height, Stem Diameter and Concentrations of Chlorophylls, Sugars, Amino Acids, and Proteins.

    Science.gov (United States)

    García-Jiménez, Atonaltzin; Gómez-Merino, Fernando C; Tejeda-Sartorius, Olga; Trejo-Téllez, Libia I

    2017-01-01

    Lanthanum (La) is considered a beneficial element, capable of inducing hormesis. Hormesis is a dose-response relationship phenomenon characterized by low-dose stimulation and high-dose inhibition. Herein we tested the effect of 0 and 10 μM La on growth and biomolecule concentrations of seedlings of four sweet bell pepper (Capsicum annuum L.) varieties, namely Sven, Sympathy, Yolo Wonder, and Zidenka. Seedling evaluations were performed 15 and 30 days after treatment applications (dat) under hydroponic greenhouse conditions. Seedling height was significantly increased by La, growing 20% taller in Yolo Wonder plants, in comparison to the control. Similarly, La significantly enhanced shoot diameter, with increases of 9 and 9.8% in measurements performed 15 and 30 dat, respectively, as compared to the control. Likewise, La-treated seedlings had a higher number of flower buds than the control. An increase in the number of leaves because of La application was observed in Yolo Wonder seedlings, both 15 and 30 dat, while leaf area was augmented in this variety only 30 dat. Nevertheless, La did not affect dry biomass accumulation. La effects on biomolecule concentration were differential over time. In all varieties, La stimulated the biosynthesis of chlorophyll a, b and total 15 dat, though 30 dat only the varieties Sympathy and Yolo Wonder showed enhanced concentrations of these molecules because of La. Total soluble sugars increased in La-treated seedlings 30 dat. Interestingly, while most varieties exposed to La showed a reduction in amino acid concentration 15 dat, the opposite trend was observed 30 dat. Importantly, in all varieties evaluated, La stimulated soluble protein concentration 30 dat. It is important to note that while chlorophyll concentrations increased in all varieties exposed to La, both 15 and 30 dat, those of soluble sugars and proteins consistently increased only 30 dat, but not 15 dat. Our results confirm that La may improve seedling quality by

  10. Cellular stress response in human Müller cells (MIO-M1) after bevacizumab treatment.

    Science.gov (United States)

    Matsuda, Monique; Krempel, Paloma Gava; Marquezini, Mônica Valeria; Sholl-Franco, Alfred; Lameu, Amanda; Monteiro, Mário Luiz R; Miguel, Nádia Campos de Oliveira

    2017-07-01

    Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, is widely used in the treatment of retinal vascular diseases. However, due to the essential role Müller cell derived-VEGF plays in the maintenance of retinal neurons and glial cells, cell viability is likely to be affected by VEGF inhibition. We therefore evaluated the effect of bevacizumab-induced VEGF inhibition on Müller cells (MIO-M1) in vitro. MIO-M1 cells were cultured for 12 or 24 h in media containing bevacizumab at 0.25 or 0.5 mg/mL. Controls were cultured in medium only. Cell viability was determined with the trypan blue exclusion test and MTT assay. Caspase-3, beclin-1, glial fibrillary acidic protein (GFAP) and vimentin content were quantified by immunohistochemistry. Gene expression was evaluated by real-time quantitative PCR. Treatment with bevacizumab did not reduce MIO-M1 cell viability, but increased metabolic activity at 24 h (0.5 mg/mL) and induced apoptosis and autophagy, as shown by the increased caspase-3 levels at 12 h (0.25 and 0.5 mg/mL) and the increased beclin levels at 24 h (0.5 mg/mL). Caspase-3 mRNA was upregulated at 12 h and downregulated at 24 h in cells treated with bevacizumab at 0.25 mg/mL. Bevacizumab treatment was also associated with structural protein abnormalities, with decreased GFAP and vimentin content and upregulated GFAP and vimentin mRNA expression. Although bevacizumab did not significantly affect MIO-M1 cell viability, it led to metabolic and molecular changes (apoptosis, autophagy and structural abnormalities) suggestive of significant cellular toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Unstable $m=1$ modes of counter-rotating Keplerian discs

    CERN Document Server

    Gulati, Mamta; Sridhar, S

    2012-01-01

    We study the linear $m=1$ counter-rotating instability in a two-component, nearly Keplerian disc. Our goal is to understand these \\emph{slow} modes in discs orbiting massive black holes in galactic nuclei. They are of interest not only because they are of large spatial scale--and can hence dominate observations--but also because they can be growing modes that are readily excited by accretion events. Self-gravity being nonlocal, the eigenvalue problem results in a pair of coupled integral equations, which we derive for a two-component softened gravity disc. We solve this integral eigenvalue problem numerically for various values of mass fraction in the counter-rotating component. The eigenvalues are in general complex, being real only in the absence of the counter-rotating component, or imaginary when both components have identical surface density profiles. Our main results are as follows: (i) the pattern speed appears to be non negative, with the growth (or damping) rate being larger for larger values of the ...

  12. The conformational flexibility of the antibiotic virginiamycin M(1).

    Science.gov (United States)

    Dang, Jason; Metzger, Robert P; Brownlee, Robert T C; Ng, Chai Ann; Bergdahl, Mikael; Separovic, Frances

    2005-07-01

    The antibiotic virginiamycin is a combination of two molecules, virginiamycin M(1) (VM1) and virginiamycin S(1) (VS1) or analogues, which function synergistically by binding to bacterial ribosomes and inhibiting bacterial protein synthesis. Both VM1 and VS1 dissolve poorly in water and are soluble in more hydrophobic solvents. We have recently reported that the 3D conformation of VM1 in CDCl(3) solution differs markedly from the conformation bound to a VM1 binding enzyme and to 50S ribosomes as found by X-ray crystallographic studies. We now report the results of further NMR studies and subsequent molecular modeling of VM1 dissolved in CD(3)CN/H(2)O and compare the structure with that in CD(3)OD and CDCl(3). The conformations of VM1 in CD(3)CN/H(2)O, CD(3)OD and CDCl(3) differ substantially from one another and from the bound form, with the aqueous form most like the bound structure. We propose that the flexibility of the VM1 molecule in response to environmental conditions contributes to its effectiveness as an antibiotic.

  13. The m=1 amplituhedron and cyclic hyperplane arrangements

    CERN Document Server

    Karp, Steven N

    2016-01-01

    The (tree) amplituhedron A(n,k,m) is the image in the Grassmannian Gr(k,k+m) of the totally nonnegative part of Gr(k,n), under a (map induced by a) linear map which is totally positive. It was introduced by Arkani-Hamed and Trnka in 2013 in order to give a geometric basis for the computation of scattering amplitudes in N=4 supersymmetric Yang-Mills theory. When k+m=n, the amplituhedron is isomorphic to the totally nonnegative Grassmannian, and when k=1, the amplituhedron is a cyclic polytope. While the case m=4 is most relevant to physics, the amplituhedron is an interesting mathematical object for any m. In this paper we study it in the case m=1. We start by taking an orthogonal point of view and define a related "B-amplituhedron" B(n,k,m), which we show is isomorphic to A(n,k,m). We use this reformulation to describe the amplituhedron in terms of sign variation. We then give a cell decomposition of the amplituhedron A(n,k,1) using the images of a collection of distinguished cells of the totally nonnegative ...

  14. Abundances of Planetary Nebula M1-42

    CERN Document Server

    Pottasch, S R; Roellig, T L

    2007-01-01

    The spectra of the planetary nebula M1-42 is reanalysed using spectral measurements made in the mid-infrared with the Spitzer Space Telescope. The aim is to determine the chemical composition of this object. We also make use of ISO, IUE and ground based spectra. Abundances determined from the mid- and far-infrared lines, which are insensitive to electron temperature, are used as the basis for the determination of the composition, which are found to substantially differ from earlier results. High values of neon, argon and sulfur are found. They are higher than in other PN, with the exception of NGC6153, a nebula of very similar abundances. The high values of helium and nitrogen found indicate that the second dredge-up and hot bottom burning has occurred in the course of evolution and that the central star was originally more massive than 4Msun. The present temperature and luminosity of the central star is determined and at first sight may be inconsistent with such a high mass.

  15. Thermoelectric waste heat recovery from an M1 Abrams tank

    Science.gov (United States)

    Stokes, C. David; Thomas, Peter M.; Baldasaro, Nicholas G.; Mantini, Michael J.; Venkatasubramanian, Rama; Barton, Michael D.; Cardine, Christopher V.; Walker, Grayson W.

    2012-06-01

    The addition of advanced sensors, targeting systems and electronic countermeasures to military vehicles has created a strategic need for additional electric power. By incorporating a thermoelectric (TE) waste heat recovery system to convert available exhaust heat to electricity, increased electric power needs can be met without reducing the energy efficiency of the vehicle. This approach allows existing vehicles to be upgraded without requiring a complete re-design of the engine and powertrain to support the integration of advanced electronic sensors and systems that keep the performance at the state of the art level. RTI has partnered with General Dynamics Land Systems and Creare, Inc. under an Army Research Lab program to develop a thermoelectric exhaust waste heat recovery system for the M1 Abrams tank. We have designed a reduced-scale system that was retrofitted to the tank and generated 80W of electric power on the vehicle operating on a test track by capturing a portion of the exhaust heat from the Honeywell/Lycoming AGT-1500 gas turbine engine.

  16. Structural damage and functional reorganization in ipsilesional m1 in well-recovered patients with subcortical stroke.

    Science.gov (United States)

    Zhang, Jing; Meng, Liangliang; Qin, Wen; Liu, Ningning; Shi, Fu-Dong; Yu, Chunshui

    2014-03-01

    Both structural atrophy and functional reorganization of the primary motor cortex (M1) have been reported in patients with subcortical infarctions affecting the motor pathway. However, the relationship between structural impairment and functional reorganization in M1 remains unclear. Twenty-six patients exhibiting significant recovery after subcortical infarctions were investigated using multimodal MRI techniques. Structural impairment was assessed via cortical thickness, and functional reorganization was analyzed using task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity. Compared with healthy controls, patients with stroke exhibited reduced cortical thickness in the ipsilesional M1; however, this region exhibited increased task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity in these patients. Patients with stroke demonstrated increased task-evoked activation in another ipsilesional M1 region, in which increased amplitude of low-frequency fluctuation and resting-state functional connectivity were observed. The structural and functional changes in M1 were located selectively in the ipsilesional hemisphere. We provide convincing evidence that indicates extensive functional reorganization in the ipsilesional M1 of patients with chronic subcortical infarctions, including the structurally impaired M1 region.

  17. Comparative genomics of Streptococcus pyogenes M1 isolates differing in virulence and propensity to cause systemic infection in mice.

    Science.gov (United States)

    Fiebig, Anne; Loof, Torsten G; Babbar, Anshu; Itzek, Andreas; Koehorst, Jasper J; Schaap, Peter J; Nitsche-Schmitz, D Patric

    2015-09-01

    Streptococcus pyogenes serotype M1 is a frequent cause of severe infections in humans. Some M1 isolates are pathogenic in mice and used in studies on infection pathogenesis. We observed marked differences in murine infections caused by M1 strain SF370, 5448, 5448AP or AP1 which prompted us to sequence the whole genome of isolates 5448 and AP1 for comparative analysis. Strain 5448 is known to acquire inactivating mutations in the CovRS two-component system during mouse infection, producing hypervirulent progeny such as 5448AP. Isolates AP1 and 5448AP, more than 5448, caused disseminating infections that became systemic and lethal. SF370 was not pathogenic. Phages caused gross genetic differences and increased the gene content of AP1 by 8% as compared to 5448 and SF370. Each of six examined M1 genomes contained two CRISPR-Cas systems. Phage insertion destroyed a type II CRISPR-Cas system in AP1 and other strains of serotypes M1, M3, M6 and M24, but not in M1 strains 5448, SF370, MGAS5005, A20 or M1 476. A resulting impaired defence against invading genetic elements could have led to the wealth of phages in AP1. AP1 lacks genetic features of the MGAS5005-like clonal complex including the streptodornase that drives selection for hypervirulent clones with inactivated CovRS system. Still, inactivating mutations in covS were a common genetic feature of AP1 and the MGAS5005-like isolate 5448AP. Abolished expression of the cysteine proteinase SpeB, due to CovRS inactivation could be a common cause for hypervirulence of the two isolates. Moreover, an additional protein H-coding gene and a mutation in the regulator gene rofA distinguished AP1 form other M1 isolates. In conclusion, hypervirulence of S. pyogenes M1 in mice is not limited to the MGAS5005-like genotype. Copyright © 2015 Elsevier GmbH. All rights reserved.

  18. Tramadol differentially regulates M1 and M2 macrophages from human umbilical cord blood.

    Science.gov (United States)

    Zhang, Jun; Chen, Liang; Sun, Yunyun; Li, Yuanhai

    2017-03-17

    Tramadol is an analgesic drug and relieves pain through activating μ-opioid receptors and inhibiting serotonin and noradrenaline reuptake. Emerging evidence shows that it also stimulates immune cells, including NK cells, splenocytes, and lymphocytes, and elevates IL-2 production. However, it remains unknown whether and how tramadol directly affects macrophages. To answer these questions, we collected human umbilical cord blood, isolated macrophages, and examined their responses to tramadol. Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-γ and IL-4. Interestingly, tramadol inhibits production and secretion of cytokines in M1 macrophages, but facilitates the production of inflammation-responding molecules, synthesized in M2 macrophages. We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol. Therefore, this study reveals that tramadol regulates inflammation by inhibiting M1 macrophages (killing process), but promoting the function of M2 macrophages (healing process).

  19. Muscarinic M1 receptors regulate propofol modulation of GABAergic transmission in rat ventrolateral preoptic neurons.

    Science.gov (United States)

    Zhang, Yu; Yu, Tian; Liu, Yang; Qian, Kun; Yu, Bu-Wei

    2015-04-01

    GABAergic neurons within the ventrolateral preoptic area (VLPO) play an important role in sleep-wakefulness regulation. Propofol, a widely used systemic anesthetic, has lately been reported to excite noradrenaline (NA)-inhibited type of VLPO neurons. Present study tested if acetylcholine system takes part in the propofol modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in mechanically dissociated rat VLPO neurons using a conventional whole-cell patch clamp technique. Propofol reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that propofol acts presynaptically to decrease the probability of spontaneous GABA release. The propofol action on GABAergic mIPSC frequency was completely blocked by atropine, a nonselective muscarinic acetylcholine (mACh) receptor antagonist, and pirenzepine, a selective M1 receptor antagonist. These results suggest that propofol acts on M1 receptors on GABAergic nerve terminals projecting to VLPO neurons to inhibit spontaneous GABA release. The M1 receptor-mediated modulation of GABAergic transmission onto VLPO neurons may contribute to the regulation of loss of consciousness induced by propofol.

  20. Chronic treatment with simvastatin upregulates muscarinic M1/4 receptor binding in the rat brain.

    Science.gov (United States)

    Wang, Q; Zengin, A; Ying, W; Newell, K A; Wang, P; Yeo, W; Wong, P T-H; Yenari, M A; Huang, X-F

    2008-06-26

    Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [(3)H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [(3)H]pirenzepine binding, predominantly in the prefrontal cortex (171%, Ppirenzepine binding were observed in the examined regions following simvastatin (10 mg/kg/day) treatment. Our results also provide strong evidence that chronic simvastatin administration, especially at a low dosage, up-regulates M1/4 receptor binding, which is likely to be independent of its muscarinic agonist-like effect. Alterations in [(3)H]pirenzepine binding in the examined brain areas may represent the specific regions that mediate the clinical effects of simvastatin treatment on cognition and memory via the muscarinic cholinergic system. These findings contribute to a better understanding of the critical roles of simvastatin in treating neurodegenerative disorders, via muscarinic receptors.

  1. Tillering of two wheat genotypes as affected by phosphorus levels=Perfilhamento de dois genótipos de trigo em função de doses de fósforo

    Directory of Open Access Journals (Sweden)

    Leonardo Theodoro Büll

    2012-07-01

    Full Text Available Tillering plays an important role in wheat yield potential and it is affected by genotype and environmental conditions. This work aimed to study the effects of phosphorus levels on tiller emergence, survival and contribution to yield potential of two wheat cultivars. The experiment was carried out under greenhouse conditions in Botucatu, São Paulo State, Brazil. A 2 x 5 factorial randomized block design with four replications was applied. Two wheat cultivars (IAC 370 and IAC 375 and five phosphorus levels (0, 150, 300, 450 and 600 mg dm-3 were evaluated in pots with 10 dm3 of a clayey Oxisol. Higher P levels increased tiller emergence, survival and yield, especially for secondary tillers. Tiller abortion levels were higher in IAC 370 cultivar whereas retention of formed tillers was higher in IAC 375. A participação de perfilhos na produção de grãos é de grande importância para a cultura do trigo, sendo influenciável pelas características do genótipo e condições do ambiente. O presente trabalho teve o objetivo de estudar o efeito de doses de fósforo (P na emissão, sobrevivência e contribuição produtiva de perfilhos de duas cultivares de trigo. O experimento foi conduzido em casa de vegetação em Botucatu, Estado de São Paulo. Foi adotado um esquema fatorial 2 x 5 em blocos casualizados com quatro repetições, sendo avaliadas duas cultivares de trigo (IAC 370 e IAC 375 e cinco doses de P (0, 150, 300, 450 e 600 mg dm-3. Quanto maior a dose de P, maior a emissão, a sobrevivência e a participação de perfilhos na produ��ão total de grãos, em especial para perfilhos secundários. A cultivar IAC 370 apresentou altas taxas de abortamento de perfilhos, enquanto a IAC 375 manteve grande parte dos perfilhos emitidos.

  2. Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients

    Institute of Scientific and Technical Information of China (English)

    Kentaro Ichioka; Kanji Nagahama; Kazutoshi Okubo; Takeshi Soda; Osamu Ogawa; Hiroyuki Nishiyama

    2009-01-01

    Glutathione S-transferases (GSTs), superoxide dismutase 2 (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase T1 (GSTT1)-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction (PCR). Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. A significantly better response to varicocelectomy was found in patients with the GSTTI-wt genotype (63.2%) and NQO1-Ser/Ser genotype (80.0%) than in those with GSTT1-null genotype (35.3%) and NQO1-Pro/Pro or NQO1-Pro/Ser genotype (45.2%), respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicoceleetomy requires further investigation.

  3. STUDY OF THE DELETION MUTATION OF GLUTATHIONE S TRANSFERASE M1 GENE AND ITS ROLE IN SUSCEPTIBILITY TO HEPATOCELLULAR CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objection: To investigate the glutathione S transferase M1 (GSTM1) gene inherent deletion and its relation to prevalence of hepatocellular carcinoma (HCC) in Guangxi, China. Methods: The GSTM1 gene polymorphism of 120 HCC patients and 100 healthy subjects both from the same high aflatoxin B1 (AFB1) contaminated area were detected using PCR technique with special primers. Another 40 patients from AFB1 low risk area were also tested. Results: In HCC high risk area, it was found that the frequencies of GSTM1 null genotype in HCC patients and healthy subjects were 59% and 51% respectively, with no significant difference. However, the frequency of GSTM1-null genotype in control group from AFB1 low risk area was lower than those from high risk area (P<0.01). Conclusion: Populations in this HCC endemic region show a higher rate of GSTM1-null genotype, which may be partially responsible for the susceptibility to AFB1 induced HCC. But the detoxification effect of GSTM1 alone is not sufficient to resist the genetic toxicity of AFB1, especially in those people who expose to excess AFB1. The GSTM1 gene deletion would not be suitable as an independent predictor of susceptibility to HCC.

  4. Modulation of Effects of Intermittent Theta Burst Stimulation Applied Over Primary Motor Cortex (M1) by Conditioning Stimulation of the Opposite M1

    Science.gov (United States)

    Ragert, Patrick; Camus, Mickael; Vandermeeren, Yves; Dimyan, Michael A.; Cohen, Leonardo G.

    2009-01-01

    The excitability of the human primary motor cortex (M1) as tested with transcranial magnetic stimulation (TMS) depends on its previous history of neural activity. Homeostatic plasticity might be one important physiological mechanism for the regulation of corticospinal excitability and synaptic plasticity. Although homeostatic plasticity has been demonstrated locally within M1, it is not known whether priming M1 could result in similar homeostatic effects in the homologous M1 of the opposite hemisphere. Here, we sought to determine whether down-regulating excitability (priming) in the right (R) M1 with 1-Hz repetitive transcranial magnetic stimulation (rTMS) changes the excitability-enhancing effect of intermittent theta burst stimulation (iTBS) applied over the homologous left (L) M1. Subjects were randomly allocated to one of four experimental groups in a sham-controlled parallel design with real or sham R M1 1-Hz TMS stimulation always preceding L M1 iTBS or sham by about 10 min. The primary outcome measure was corticospinal excitability in the L M1, as measured by recruitment curves (RCs). Secondary outcome measures included pinch force, simple reaction time, and tapping speed assessed in the right hand. The main finding of this study was that preconditioning R M1 with 1-Hz rTMS significantly decreased the excitability-enhancing effects of subsequent L M1 iTBS on RCs. Application of 1-Hz rTMS over R M1 alone and iTBS over L M1 alone resulted in increased RC in L M1 relative to sham interventions. The present findings are consistent with the hypothesis that homeostatic mechanisms operating across hemispheric boundaries contribute to regulate motor cortical function in the primary motor cortex. PMID:19474173

  5. HPV genotypes concordance between sex partners.

    Science.gov (United States)

    Benevolo, M; Mottolese, M; Marandino, F; Carosi, M; Diodoro, M G; Sentinelli, S; Visca, P; Rollo, F; Mariani, L; Vocaturo, G; Sindico, R; Di Giannuario, D; Perrone Donnorso, R; Pellicciotta, M; Vocaturo, A

    2007-12-01

    The HPV genotype concordance in the sexual couples could support the sexual viral transmission of HPV infection. The present study contains a case-report of a stable Italian sex couple harbouring the same five HPV genotypes in their genital samples. The female partner, affected by vulvar condilomatosis, evidenced positivity in her cervicovaginal scraping with high risk HPV DNA Hybrid Capture 2 test and was negative at liquid-based performed Pap Test and at colposcopic examination. The male partner was clinically healthy regarding his external genitalia. In both male and female genital scrapings, the following HPV genotypes were detected by means of a PCR-based assay: 6, 16, 53, 73 and 84. This considerably high genotype concordance does not appear to be casual and supports, in our opinion, the hypothesis that genital HPV types are sexually transmitted agents

  6. The TNM 8 M1b and M1c classification for non-small cell lung cancer in a cohort of patients with brain metastases.

    Science.gov (United States)

    Nieder, C; Hintz, M; Oehlke, O; Bilger, A; Grosu, A L

    2017-09-01

    According to the recent TNM 8 classification, patients with metastatic non-small cell lung cancer (NSCLC) and single extrathoracic metastasis should be classified as stage M1b, while those with 2 or more metastases comprise stage M1c. The purpose of this study was to analyze the impact of this classification in patients with brain metastases. This retrospective study included 172 patients treated with individualized approaches. Actuarial survival was calculated. Uni- and multivariate analyses were performed. Thirty patients (17%) were staged as M1b. Those with squamous cell cancer were more likely to harbor M1b disease (29%, adenocarcinoma 14%, other histology 17%, p = 0.16). Median survival was 5.4 months (8.0 months in case of M1b disease and 4.5 months in case of M1c disease, p = 0.001). Multivariate analysis confirmed the role of M1b stage. M1b patients managed with upfront surgery or radiosurgery had significantly longer median survival than those who received whole-brain irradiation (21.0 vs. 3.5 months, p = 0.0001) and the potential to survive beyond 5 years. We found the M1b classification to provide clinically relevant information. The multivariate analysis suggested that patients with M1b disease, better performance status and younger age have better survival.

  7. Experimental Conditions: SE37_S18_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S18 PSEUDO: Unlabeled and labeled Medicago samples for metabolite annotation using ShiftedIonsFind...17_M1), and for Medicago samples labeled by 13C (S05_M1), 15N (S07_M1), 28O (S10_M1), and 34S (S13_M1) are used. SE37_DS4 Labeled peak search by ShiftedIonsFinder ...

  8. Silos experimentais para avaliação da silagem de três genótipos de girassol (Helianthus annuus L. Evaluation of sunflower (Helianthus annuus L. silage of three genotypes as affected by experimental silos

    Directory of Open Access Journals (Sweden)

    L.G.R. Pereira

    2005-10-01

    Full Text Available Três tipos de silos experimentais foram utilizados para a avaliação das silagens de três genótipos de girassol: A silo padrão com válvula de Bunsen; B silo dotado de compartimento para efluentes e C silo com válvula de Bunsen e compartimento para efluentes. O delineamento experimental foi inteiramente ao acaso, em esquema fatorial 3×3 (genótipos × tipos de silos com três repetições. As características avaliadas foram: matéria seca (MS, densidade, proteína bruta (PB, nitrogênio amoniacal (N-NH3/N-T, pH, carboidratos solúveis (CHO, ácidos orgânicos, constituintes da parede celular, extrato etéreo (EE e digestibilidade in vitro da matéria seca (DIVMS. As silagens obtidas nos silos B e C apresentaram os maiores valores de MS e menores de NH3/N-T. Os valores de pH se equivaleram nos três tipos de silos, enquanto os teores de CHO foram menores para as silagens obtidas nos silos B e C. Os silos dotados de compartimento para efluentes apresentaram os maiores valores de ácido láctico. As frações fibrosas, EE e DIVMS não sofreram influência dos tipos de silos. A presença ou ausência da válvula de Bunsen não influenciou os parâmetros avaliados. A presença do compartimento para efluentes afetou a qualidade e o valor nutritivo da silagem de girassol.A completely randomized design in a 3×3 factorial scheme was used to evaluate the effect of three genotypes and three types of silos on sunflower silage. The silos were: A- silo with Bunsen valve; B- silo with effluent-collecting equipment; and C- silo with both Bunsen valve and effluent-collecting equipment. The parameters evaluated were: dry matter (DM, crude protein (CP, ammonia nitrogen (N-NH3/T-N, pH, soluble carbohydrates (CHO, organic acids, cell wall constituents, ether extract and in vitro dry matter digestibility (IVDMD. The silage from silos B and C had higher values of DM and lower levels of N-NH3/T-N. The pH value was the same for all silos, while the CHO was the

  9. Effect of pirenzepine, a muscarinic M1 receptor antagonist, on amygdala kindling in rat.

    Science.gov (United States)

    Eşkazan, E; Aker, R; Onat, F; Köseoğlu, S; Gören, M Z; Hasanoğlu, A

    1999-11-01

    Kindling, an animal model of complex partial seizures with secondary generalization, is performed by daily application of low-intensity electrical brain stimulation. The purpose of this study was to investigate the role of muscarinic M1 receptors on amygdala kindling in the rat. Bipolar nichrome stimulation and recording electrodes were stereotaxically implanted into the right and left basolateral amygdala. Extradural recording electrodes were also placed bilaterally in the skull over the cortex. Amygdala stimulation was applied twice daily at the current intensity of afterdischarge threshold. Seizure intensity was graded by using Racine's standard five-stage scale. In the first group of experiments, saline or pirenzepine (10, 25, 50 and 100 nmol), a muscarinic M1 receptor antagonist, was injected intracerebroventricularly 1 h before the electrical stimulation. In the second group of experiments, rats were kindled to full stage 5 seizures. After a recovery period, 50 nmol of pirenzepine was administered intracerebroventricularly to kindled animals. In the first group of experiments, none of the animals pretreated with the doses of 50 and 100 nmol of pirenzepine reached a stage 5 seizure. Pirenzepine significantly retarded kindling seizure development and increased the total number of stimulations required to reach the first stage 5 seizure. Afterdischarge duration was also reduced in the pirenzepine 10 nmol group as compared with that in the saline-pretreated group. In the second group, seizure stage and afterdischarge duration were not affected by pirenzepine in fully-kindled animals. The findings of this study suggest that muscarinic M1 receptors may have a critical role in the development of kindling epileptic activity, but not in already kindled seizures.

  10. APOE Genotyping, Cardiovascular Disease

    Science.gov (United States)

    ... Home Visit Global Sites Search Help? APOE Genotyping, Cardiovascular Disease Share this page: Was this page helpful? Also ... of choice to decrease the risk of developing cardiovascular disease (CVD) . However, there is a wide variability in ...

  11. The Reaction Dynamics of the Reactions Ba+CmH2m+1Br(m=1,2,3,4,5)

    Institute of Scientific and Technical Information of China (English)

    韩克利; 郑锡光; 张瑞勤; 孙本繁; 何国钟; 楼南泉

    1994-01-01

    The internal energy distributions of the nascent BaBr products formed in the reactions ofBa+BrR(R=CH3,C2H5,C3H7,C4H9,C5H11) under the single collision condition have been first studied bylaser-induced fluorescence method.With computer simulations of the experimental spectra,we obtained thevibrational distributions of the BaBr products,and found that the vibrational excitation and reaction cross-section increase with the number of the carbon atoms in the alkyl radical R.The quasitriatomic LEPS poten-tial of the Ba+CH3 reaction has been deduced reversely from the experimental results.The dynamics of thereactions Ba+BrR have been studied by the classical trajectory calculations based on the model LEPS poten-tials.It is concluded that the mass factor and the C-Br bond strength are the major factors affecting the rela-tionship between vibrational excitation and reaction cross-section with the number of the carbon atoms in thealkyl radical R.Furthermore,we obtained all the LEPS potentials of the reactive systems Ba+CmH2m+1 andconfirmed its reliability with ab initio calculations.

  12. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo.

    Directory of Open Access Journals (Sweden)

    Michael Zhang

    Full Text Available Tumor-associated macrophages (TAMs represent an important cellular subset within the glioblastoma (WHO grade IV microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo.

  13. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo

    Science.gov (United States)

    Kahn, Suzana A.; Azad, Tej D.; Gholamin, Sharareh; Xu, Chelsea Y.; Liu, Jie; Achrol, Achal S.; Richard, Chase; Sommerkamp, Pia; Schoen, Matthew Kenneth; McCracken, Melissa N.; Majeti, Ravi; Weissman, Irving; Mitra, Siddhartha S.; Cheshier, Samuel H.

    2016-01-01

    Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo. PMID:27092773

  14. Citrus tristeza virus: Evolution of Complex and Varied Genotypic Groups

    Science.gov (United States)

    Harper, S. J.

    2013-01-01

    Amongst the Closteroviridae, Citrus tristeza virus (CTV) is almost unique in possessing a number of distinct and characterized strains, isolates of which produce a wide range of phenotype combinations among its different hosts. There is little understanding to connect genotypes to phenotypes, and to complicate matters more, these genotypes are found throughout the world as members of mixed populations within a single host plant. There is essentially no understanding of how combinations of genotypes affect symptom expression and disease severity. We know little about the evolution of the genotypes that have been characterized to date, little about the biological role of their diversity and particularly, about the effects of recombination. Additionally, genotype grouping has not been standardized. In this study we utilized an extensive array of CTV genomic information to classify the major genotypes, and to determine the major evolutionary processes that led to their formation and subsequent retention. Our analyses suggest that three major processes act on these genotypes: (1) ancestral diversification of the major CTV lineages, followed by (2) conservation and co-evolution of the major functional domains within, though not between CTV genotypes, and (3) extensive recombination between lineages that have given rise to new genotypes that have subsequently been retained within the global population. The effects of genotype diversity and host-interaction are discussed, as is a proposal for standardizing the classification of existing and novel CTV genotypes. PMID:23630519

  15. BDNF genotype influence the efficacy of rTMS in stroke patients.

    Science.gov (United States)

    Uhm, Kyeong Eun; Kim, Yun-Hee; Yoon, Kyung Jae; Hwang, Jung Min; Chang, Won Hyuk

    2015-05-06

    Brain-derived neurotrophic factor (BDNF) genotype can influence neural response to repetitive transcranial magnetic stimulation (rTMS) in normal individuals. In this study we established personalized stimulus intensity of facilitatory rTMS according to BDNF genotype in stroke patients. Twenty-two chronic stroke patients were enrolled. All patients underwent three different sessions of rTMS over the ipsilesional M1 in randomized order with a washout period exceeding 24h: first condition, high-frequency rTMS with sub-threshold intensity; second condition, high-frequency rTMS with supra-threshold intensity; third condition, sham rTMS. Cortical excitability in the affected hemisphere was assessed with motor evoked potentials (MEPs) before and after stimulation. Data were analyzed according to BDNF genotype. Six [27.3%] and 16 [72.7%] participants were classified in the Val/Val group and Met allele group, respectively. In each group, significant increases were observed in the amplitude of MEPs after the stimulation in the first and second conditions (prTMS is used for the modulation of cortical excitability in patients with chronic stroke.

  16. Growth and yield components of wheat genotypes as influenced by potassium and farm yard manure on a saline sodic soil

    Directory of Open Access Journals (Sweden)

    Muhammad Ashraf, Muhammad Afzal

    2011-11-01

    Full Text Available The adequate supply of mineral nutrients through chemical fertilizers and manure may help to sustain the crop productivity and ensure plant survival under salinity stress. A field study was conducted on saline sodic soil (ECe = 13 dS m-1, SAR 23.3 (mmol L-11/2, pH = 8.6 of surface 15 cm layer to quantify the effects of potassium (K and farm yard manure (FYM on two wheat genotypes differing in salinity tolerance. Three K levels (0, 80, 120 kg ha-1 and two FYM levels (0, 10 t ha-1 were tested using randomized compete block design (RCBD with three replications. The application of K along with FYM reduced Na+ uptake and accumulation in plant tissue. The K concentration and K+/ Na+ ratio were significantly improved in both wheat genotypes with the supplementation of K and FYM. The grain yield was improved by 40-156% in salt tolerant genotype and 46-206% in salt sensitive genotype with added K and FYM. Similar trend was observed in yield components. Ameliorative effects of added K and FYM were more marked in salt sensitive genotype (Auqab-2000 than in salt tolerant (Inqlab-91. Grain yield of salt sensitive and salt tolerant wheat genotypes was positively correlated with leaf K+ concentration determined at various treatments. Addition of K along with FYM decreased sodium adsorption ratio (SAR and electrical conductivity (EC of soil particularly in upper layers. Therefore, it is concluded that K along with FYM could help to alleviate deleterious effects of salts and thus improve the productivity of salt affected soils.

  17. Glutathione-S-transferase M1 polymorphisms on the susceptibility to esophageal cancer among three Chinese minorities: Kazakh, Tajik and Uygur

    Institute of Scientific and Technical Information of China (English)

    Xiao-Mei Lu; Ting Yang; Shu-Yong Xu; Hao Wen; Xing Wang; Zhi-Hui Ren; Yan Zhang; Wei Wang

    2006-01-01

    AIM: To investigate the glutathione-S-transferase M1 (GSTM1) polymorphisms in three Chinese minorities,Kazakh, Uygur, and Tajik; and the pathological significance of GSTM1 polymorphisms in esophageal carcinogenesis in Kazakh.METHODS: A total of 1121 blood samples (442 males and 679 females) were obtained from healthy Kazakh (654), Uygur (412) and Tajik (55). Primary esophageal squamous cell cancer (ESCC) tissues from Kazakh were obtained from 116 patients who underwent surgery.GSTM1 polymorphisms were analyzed by a combined approach of PCR and electrophoresis techniques.RESULTS: GSTM1 null genotype was found in 62.63% Uygur, 50.91% Tajik and 47.40% Kazakh. A significantly higher frequency of GSTM1 null genotype in Uygur was observed compared with Kazakh (OR: 1.859, 95% CI: 1.445 -2.391, χ2 = 23.71, P = 0.000). In addition,GSTM1 null genotype was found in 23.53% of welldifferentiated ESCC in Kazakh, in 49.23% of poorly differentiated ESCC, with a significant difference (OR:3.152, 95% CI: 1.403-7.080, χ2 = 8.018, P = 0.007).CONCLUSION: There is a marked difference in the frequency of common GSTM1 null genotype between Uygur and Kazakh. GSTM1 null genotype is associated with differentiation of ESCC in Kazakh.

  18. Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Chan-on W

    2015-04-01

    Full Text Available Waraporn Chan-on,1 Nguyen Thi Bich Huyen,2 Napat Songtawee,3 Wilasinee Suwanjang,1 Supaluk Prachayasittikul,3 Virapong Prachayasittikul2 1Center for Research and Innovation, 2Department of Clinical Microbiology and Applied Technology, 3Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand Purpose: Fork head box M1 (FoxM1 is an oncogenic transcription factor frequently elevated in numerous cancers, including cholangiocarcinoma (CCA. A growing body of evidence documents its diverse functions contributing to tumorigenesis and cancer progression. As such, discovery of agents that can target FoxM1 would be valuable for the treatment of CCA. The quinoline-based compounds, namely clioquinol (CQ and nitroxoline (NQ, represent a new class of anticancer drug. However, their efficacy and underlying mechanisms have not been elucidated in CCA. In this study, anticancer activities and inhibitory effects of CQ and NQ on FoxM1 signaling were explored using CCA cells.Methods: The effects of CQ and NQ on cell viability and proliferation were evaluated using the colorimetric 3-(4,5-dimethylthiazol-2yl-5-(3-carboxymethoxyphenyl-(4-sulfophenyl-2H-tetrazolium (MTS assay. Colony formation and cell migration affected by CQ and NQ were investigated using a clonogenic and a wound healing assay, respectively. To demonstrate the agents’ effects on FoxM1 signaling, expression levels of the target genes were quantitatively determined using real-time polymerase chain reaction.Results: CQ and NQ significantly inhibited cell survival of HuCCT1 and Huh28 in a dose- and a time-dependent fashion. Further investigations using the rapidly proliferating HuCCT1 cells revealed significant suppression of cell proliferation and colony formation induced by low doses of the compounds. Treatment of CQ and NQ repressed expression of cyclin D1 but enhanced expression of p21. Most importantly, upon CQ and NQ treatment

  19. Glutathione-S-transferases M1/T1 gene polymorphisms and endometriosis: a meta-analysis in Chinese populations.

    Science.gov (United States)

    Chen, Xin-Ping; Xu, Da-Feng; Xu, Wei-Hua; Yao, Jia; Fu, Sheng-Miao

    2015-01-01

    In view of the controversies surrounding the glutathione-S-transferases (GST) M1/T1-endometriosis association, a meta-analysis of the GSTM1/GSTT1 genetic association studies of endometriosis was performed in Chinese populations. PubMed, Springer Link, OvidSP, and Chinese databases were searched for related studies. A total of nine studies on GSTM1-endometriosis involved 874 cases and 997 controls, and five studies on GSTT1 involved 404 cases and 513 controls were included in this meta-analysis. Overall, the null genotype of GSTM1/GSTT1 was significantly related to endometriosis risk in Chinese populations (GSTM1, OR = 2.21, 95% CI: 1.22-4.01; GSTT1, OR = 2.31, 95% CI: 1.34-3.99). In subgroup analyses stratified by ethnicity and source of controls, the same results were observed in Chinese Han and population-based studies. The sensitivity analysis confirmed the reliability and stability of the meta-analysis. No publication bias was found among studies by Egger's test. In conclusion, our meta-analysis supports that the GSTM1/GSTT1 null genotype might contribute to individual susceptibility to endometriosis in Chinese populations, especially in Chinese Han.

  20. vacA Genotype Status of Helicobacter pylori Isolated from Foods with Animal Origin

    Directory of Open Access Journals (Sweden)

    Elnaz Saeidi

    2016-01-01

    Full Text Available According to controversial theories and results of studies, foods with animal origins play an important role in the transmission of H. pylori to human. The aim of this study was to determine the distribution of vacA genotypes of H. pylori, isolated from milk and meat samples of cow, sheep, goat, camel, and buffalo. Eight hundred and twenty raw milk and meat samples were collected from various parts of Iran. Samples were cultured and those found positive for H. pylori were analyzed for the presence of various genotypes of vacA gene. Out of 420 milk and 400 meat samples, 92 (21.90% and 105 (26.25% were positive for H. pylori, respectively. The most commonly detected genotypes in the vacA gene were s1a (86.80%, m1a (79.18%, s1b (69.54%, and m1b (63.45% and detected combined genotypes were mostly m1as1a (68.52%, m1as1b (60.40%, m1bs1b (55.83%, and m1bs1a (53.29%. High presence of bacteria in the milk and meat samples of sheep represents that sheep may be the natural host of H. pylori. High presence of H. pylori strains in milk and meat samples similar to vacA genotypes in human being suggests that milk and meat samples could be the sources of bacteria for human.

  1. Axiom turkey genotyping array

    Science.gov (United States)

    The Axiom®Turkey Genotyping Array interrogates 643,845 probesets on the array, covering 643,845 SNPs. The array development was led by Dr. Julie Long of the USDA-ARS Beltsville Agricultural Research Center under a public-private partnership with Hendrix Genetics, Aviagen, and Affymetrix. The Turk...

  2. (Brassica napus L.) genotypes

    African Journals Online (AJOL)

    STORAGESEVER

    2009-10-05

    Oct 5, 2009 ... The genetic diversity and relationships among rapeseed genotypes were ... dent of environment and plant growth stage, unlimited ..... interactions that lead to the expression of particular traits .... thesis, Faculty of Agriculture, University of Novi Sad. ... in the U.S. hard red winter wheat cultivars as reveled by.

  3. The Pseudomonas syringae pv. tomato type III effector HopM1 suppresses Arabidopsis defenses independent of suppressing salicylic acid signaling and of targeting AtMIN7.

    Directory of Open Access Journals (Sweden)

    Anju Gangadharan

    Full Text Available Pseudomonas syringae pv tomato strain DC3000 (Pto delivers several effector proteins promoting virulence, including HopM1, into plant cells via type III secretion. HopM1 contributes to full virulence of Pto by inducing degradation of Arabidopsis proteins, including AtMIN7, an ADP ribosylation factor-guanine nucleotide exchange factor. Pseudomonas syringae pv phaseolicola strain NPS3121 (Pph lacks a functional HopM1 and elicits robust defenses in Arabidopsis thaliana, including accumulation of pathogenesis related 1 (PR-1 protein and deposition of callose-containing cell wall fortifications. We have examined the effects of heterologously expressed HopM1Pto on Pph-induced defenses. HopM1 suppresses Pph-induced PR-1 expression, a widely used marker for salicylic acid (SA signaling and systemic acquired resistance. Surprisingly, HopM1 reduces PR-1 expression without affecting SA accumulation and also suppresses the low levels of PR-1 expression apparent in SA-signaling deficient plants. Further, HopM1 enhances the growth of Pto in SA-signaling deficient plants. AtMIN7 contributes to Pph-induced PR-1 expression. However, HopM1 fails to degrade AtMIN7 during Pph infection and suppresses Pph-induced PR-1 expression and callose deposition in wild-type and atmin7 plants. We also show that the HopM1-mediated suppression of PR-1 expression is not observed in plants lacking the TGA transcription factor, TGA3. Our data indicate that HopM1 promotes bacterial virulence independent of suppressing SA-signaling and links TGA3, AtMIN7, and other HopM1 targets to pathways distinct from the canonical SA-signaling pathway contributing to PR-1 expression and callose deposition. Thus, efforts to understand this key effector must consider multiple targets and unexpected outputs of its action.

  4. FoxM1, a forkhead transcription factor is a master cell cycle regulator for mouse mature T cells but not double positive thymocytes.

    Directory of Open Access Journals (Sweden)

    Ling Xue

    Full Text Available FoxM1 is a forkhead box transcription factor and a known master regulator required for different phases of the cell cycle. In cell lines, FoxM1 deficient cells exhibit delayed S phase entry, aneuploidy, polyploidy and can't complete mitosis. In vivo, FoxM1 is expressed mostly in proliferating cells but is surprisingly also found in non-proliferating CD4(+CD8(+ double positive thymocytes. Here, we addressed the role of FoxM1 in T cell development by generating and analyzing two different lines of T-cell specific FoxM1 deficient mice. As expected, FoxM1 is required for proliferation of early thymocytes and activated mature T cells. Defective expression of many cell cycle proteins was detected, including cyclin A, cyclin B1, cdc2, cdk2, p27 and the Rb family members p107 and p130 but surprisingly not survivin. Unexpectedly, loss of FoxM1 only affects a few cell cycle proteins in CD4(+CD8(+ thymocytes and has little effect on their sensitivity to apoptosis and the subsequent steps of T cell differentiation. Thus, regulation of cell cycle genes by FoxM1 is stage- and context-dependent.

  5. Polymorphism of Glutathione S-transferase T1, M1 and P1 Genes in a Shanghai Population: Patients With Occupational or Non-occupational Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective Glutathione S-transferases are involved in the conjugation of xenobiotics. To explore whether GSTs polymorphisms are involved in the development of occupational or non-occupational bladder cancer, polymorphism frequencies of GSTT1, M1 and P1 were investigated in a normal population, which had been settled in a rural area in Shanghai suburb for at least 5 generations as well as in a group of patients with benzidine exposure related occupational bladder cancer in Shanghai dyestuff industry and a group of patients with non-occupational bladder cancer. Methods PCR based procedures were performed in the study populations to confirm the genotypes of GSTT1, M1 and P1. Results The polymorphisms at locus of GSTP1- A1578G in the normal population differed significantly from those in Caucasians or African Americans. All the subjects genotyped so far (n =118) bore only homogenous wild genotype (C2293/ C2293) at GSTP1 - C2293T locus. This locus seemed to be a monomorphic in Shanghai population. No significant difference in GSTT1 and GSTM1 polymorphic form frequencies could be confirmed among three groups of subjects. An overrepresentation of GSTP1 AG or GG genotype corresponding a less stable and less effective isozyme protein was detected in patients with benzidine related occupational bladder cancer, compared with that in the normal population though a statistical significance was not yet reached (P=0.09, OR=1.96, 95% CI 0.89-4.32,). Conclusion This study suggests that GSTM1 or GSTT1 homozygous deficiency genotypes and their combination do not have a clear impact on bladder cancer incidence in a Shanghai population. It seems that GSTP1 polymorphism is not associated with non-occupational bladder cancer. GSTP1 AG or GG genotype has a higher frequency in the patients with benzidine related occupational bladder cancer, and further work is needed to confirm if GSTP1 AG or GG genotype plays a role in the development of occupational bladder cancer.

  6. Hepatitis C Virus Genotypes

    Directory of Open Access Journals (Sweden)

    Kayhan Azadmanesh

    2005-09-01

    the ultimate source of the virus's genetic diversity. HCV circulates as a heterogeneous population of genetically different but closely related genomes known as the quasispecies(15.As only 30-35% of nucleotides actually differ, there is obviously considerable heterogeneity in evolutionary rates among nucleotide sites in the genome. This heterogeneity is the result of variable evolutionary constraints. The 5'-UTR contains extensive secondary RNA structure and is correspondingly the slowest evolving genomic region(16. The next slowest region is the C (Core gene, which evolves three times faster than the 5'- UTR. The envelope genes E1 and E2 constitute the most diverse genome region and evolve about nine times faster than the 5'-UTR(16, probably as a result of their presumed role in evading the host immune response. Genomic Heterogeneity and ClassificationSystemsShortly after its discovery in 1989, it became clear that HCV had substantial nucleotide sequence diversity, with only 66 to 80% overall sequencesimilarity among strains belonging to different genotypes or subtypes(17. HCV isolates show four levels of genomic variations: types, subtypes, isolates, andquasispecies. The overall sequence similarities over complete genomic sequences are at least 91% within quasispecies, approximately 79% (range, 77 to 80% between subtypes, and about 68% (range, 66 to 69% between different types. This quasispecies is composed of a group of heterogeneous RNA sequences centered around a dominant nucleotide sequence that changes, throughout the course of the infection, under the selective pressure of the host immune system(18. More than one genotype can be found in the circulations of some HCV-infected patients, particularly in individuals who have received multiple transfusions and intravenous drug users. These are referred to as mixed-genotype infections(19, 20.The lack of a routinely available cell culture system and an easily available animal model has rendered classification of HCV

  7. SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs).

    Science.gov (United States)

    Kuduk, Scott D; Beshore, Douglas C

    2014-01-01

    There is mounting evidence from preclinical and early proof-of-concept studies suggesting that selective modulation of the M1 muscarinic receptor is efficacious in cognitive models of Alzheimer's disease (AD). A number of nonselective M1 muscarinic agonists have previously shown positive effects on cognitive function in AD patients, but were limited due to cholinergic adverse events thought to be mediated by pan activation of the M2 to M5 sub-types. Thus, there is a need to identify selective activators of the M1 receptor to evaluate their potential in cognitive disorders. One strategy to confer selectivity for M1 is the identification of allosteric agonists or positive allosteric modulators, which would target an allosteric site on the M1 receptor rather than the highly conserved orthosteric acetylcholine binding site. BQCA has been identified as a highly selective carboxylic acid M1 PAM and this review focuses on an extensive lead optimization campaign undertaken on this compound.

  8. Differential effects of M1 muscarinic receptor blockade and nicotinic receptor blockade in the dorsomedial striatum on response reversal learning

    Science.gov (United States)

    Tzavos, Arianna; Jih, Jane; Ragozzino, Michael E.

    2011-01-01

    The present studies determined whether blockade of M1-like muscarinic or nicotinic cholinergic receptors in the dorsomedial striatum affects acquisition or reversal learning of a response discrimination. Testing occurred in a modified cross-maze across two consecutive sessions. In the acquisition phase, a rat learned to turn to the left or to the right. In the reversal learning phase, a rat learned to turn in the opposite direction as required during acquisition. Experiment 1 investigated the effects of the M1-like muscarinic receptor antagonist, pirenzepine infused into the dorsomedial striatum on acquisition and reversal learning. Experiment 2 examined the effects of the nicotinic cholinergic antagonist, mecamylamine injected into the dorsomedial striatum on acquisition and reversal learning. Bilateral injections of pirenzepine at 10 µg, but not 1 µg, selectively impaired reversal learning. Analysis of the errors indicated that pirenzepine treatment did not impair the initial shift, but increased reversions back to the original response choice following the initial shift. Bilateral injections of mecamylamine, 6 or 18 µg, did not affect acquisition or reversal learning. The results suggest that activation of M1 muscarinic cholinergic receptors, but not nicotinic cholinergic receptors, in the dorsomedial striatum is important for facilitating the flexible shifting of response patterns. PMID:15302131

  9. Genomic Variants Revealed by Invariably Missing Genotypes in Nelore Cattle.

    Directory of Open Access Journals (Sweden)

    Joaquim Manoel da Silva

    Full Text Available High density genotyping panels have been used in a wide range of applications. From population genetics to genome-wide association studies, this technology still offers the lowest cost and the most consistent solution for generating SNP data. However, in spite of the application, part of the generated data is always discarded from final datasets based on quality control criteria used to remove unreliable markers. Some discarded data consists of markers that failed to generate genotypes, labeled as missing genotypes. A subset of missing genotypes that occur in the whole population under study may be caused by technical issues but can also be explained by the presence of genomic variations that are in the vicinity of the assayed SNP and that prevent genotyping probes from annealing. The latter case may contain relevant information because these missing genotypes might be used to identify population-specific genomic variants. In order to assess which case is more prevalent, we used Illumina HD Bovine chip genotypes from 1,709 Nelore (Bos indicus samples. We found 3,200 missing genotypes among the whole population. NGS re-sequencing data from 8 sires were used to verify the presence of genomic variations within their flanking regions in 81.56% of these missing genotypes. Furthermore, we discovered 3,300 novel SNPs/Indels, 31% of which are located in genes that may affect traits of importance for the genetic improvement of cattle production.

  10. M1 Protein Allows Group A Streptococcal Survival in Phagocyte Extracellular Traps through Cathelicidin Inhibition

    OpenAIRE

    Lauth, Xavier; von Köckritz-Blickwede, Maren; McNamara, Case W; Myskowski, Sandra; Zinkernagel, Annelies S.; Beall, Bernard; Ghosh, Partho; Richard L Gallo; Nizet, Victor

    2009-01-01

    M1 protein contributes to Group A Streptococcus (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of M1 protein in the stimulation of neutrophil and mast cell extracellular trap formation, yet also subsequent survival of the pathogen within these DNA-based innate defense structures. Targeted mutagenesis and heterologous expression studies demonstrate M1 protein promotes resistance...

  11. Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation.

    Science.gov (United States)

    Xiang, D; Liu, C-C; Wang, M-J; Li, J-X; Chen, F; Yao, H; Yu, B; Lu, L; Borjigin, U; Chen, Y-X; Zhong, L; Wangensteen, K J; He, Z-Y; Wang, X; Hu, Y-P

    2014-05-22

    Hepatocyte transplantation as a substitute strategy of orthotopic liver transplantation is being studied for treating end-stage liver diseases. Several technical hurdles must be overcome in order to achieve the therapeutic liver repopulation, such as the problem of insufficient expansion of the transplanted hepatocytes in recipient livers. In this study, we analyzed the application of FoxM1, a cell-cycle regulator, to enhance the proliferation capacity of hepatocytes. The non-viral sleeping beauty (SB) transposon vector carrying FoxM1 gene was constructed for delivering FoxM1 into the hepatocytes. The proliferation capacities of hepatocytes with FoxM1 expression were examined both in vivo and in vitro. Results indicated that the hepatocytes with FoxM1 expression had a higher proliferation rate than wild-type (WT) hepatocytes in vitro. In comparison with WT hepatocytes, the hepatocytes with FoxM1 expression had an enhanced level of liver repopulation in the recipient livers at both sub-acute injury (fumaryl acetoacetate hydrolase (Fah)(-/-) mice model) and acute injury (2/3 partial hepatectomy mice model). Importantly, there was no increased risk of tumorigenicity with FoxM1 expression in recipients even after serial transplantation. In conclusion, expression of FoxM1 in hepatocytes enhanced the capacity of liver repopulation without inducing tumorigenesis. FoxM1 gene delivered by non-viral SB vector into hepatocytes may be a viable approach to promote therapeutic repopulation after hepatocyte transplantation.

  12. Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes

    Directory of Open Access Journals (Sweden)

    G. Karina Chimal-Ramírez

    2016-01-01

    Full Text Available Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1 and protumoral (M2 activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli.

  13. Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes

    Science.gov (United States)

    Chimal-Ramírez, G. Karina; Espinoza-Sánchez, Nancy Adriana; Chávez-Sánchez, Luis; Arriaga-Pizano, Lourdes

    2016-01-01

    Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1) and protumoral (M2) activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli. PMID:27376091

  14. SNP genotyping technologies

    DEFF Research Database (Denmark)

    Studer, Bruno; Kölliker, Roland

    2013-01-01

    for this is the availability of high-throughput platforms for multiplexed SNP genotyping. Advancements in these technologies have enabled increased flexibility and throughput, allowing for the generation of adequate SNP marker data at very competitive cost per data point.......In the recent years, single nucleotide polymorphism (SNP) markers have emerged as the marker technology of choice for plant genetics and breeding applications. Besides the efficient technologies available for SNP discovery even in complex genomes, one of the main reasons...

  15. SNP genotyping technologies

    DEFF Research Database (Denmark)

    Studer, Bruno; Kölliker, Roland

    2013-01-01

    In the recent years, single nucleotide polymorphism (SNP) markers have emerged as the marker technology of choice for plant genetics and breeding applications. Besides the efficient technologies available for SNP discovery even in complex genomes, one of the main reasons...... for this is the availability of high-throughput platforms for multiplexed SNP genotyping. Advancements in these technologies have enabled increased flexibility and throughput, allowing for the generation of adequate SNP marker data at very competitive cost per data point....

  16. Enhanced spectrofluorimetric determination of aflatoxin M1 in liquid milk after magnetic solid phase extraction

    Science.gov (United States)

    Hashemi, Mahdi; Taherimaslak, Zohreh; Rashidi, Somayeh

    2014-07-01

    A simple and sensitive method using magnetic solid phase extraction (MSPE) followed by spectrofluorimetric detection has been developed for separation and determination of aflatoxin M1 (AFM1) in liquid milk. The method is based on the extraction of AFM1 on the modified magnetic nanoparticles (MMNPs) and subsequent derivatization of extracted AFM1 to AFM1 hemi-acetal derivative (AFM2a) by reaction with trifluoroacetic acid (TFA) for spectrofluorimetric detection. Magnetic nanoparticles (MNPs) coated by 3-(trimethoxysilyl)-1-propantiol (TMSPT) and modified with 2-amino-5-mercapto-1,3,4-thiadiazole (AMT) were used as adsorbent in MSPE procedure. Influential parameters affecting the extraction efficiency were investigated and optimized. Under the optimum conditions the calibration curve for AFM1 determination showed good linearity in the range 0.030-10.0 μg L-1 (R2 = 0.9991). The repeatability and reproducibility (RSD%) for 0.050 μg L-1 of AFM1 were 4.5% and 5.3%, respectively and limit of detection limit (S/N = 3) was estimated to be 0.010 μg L-1. The developed method was successfully applied for extraction of AFM1 from spiked liquid milk and natural contaminated liquid milk. The good spiked recoveries ranging from 91.6% to 96.1% were obtained. The results demonstrated that the developed method is simple, inexpensive, accurate and remarkably free from interference effects.

  17. Influence of class M1 glutathione S-transferase (GST Mu) polymorphism on GST M1 gene expression level and tumor size in oral squamous cell carcinoma.

    Science.gov (United States)

    Koch, F P; Kämmerer, P W; Kämmerer, P; Al-Nawas, B; Brieger, J

    2010-02-01

    Glutathione S-transferases (GST) are antioxidant enzymes and oxidative stress markers in oral carcinogenesis. They present a system of polymorphic proteins. Some variants are associated with increased sensitivity to toxic compounds, as it is known for the GSTM1-null variant allele. However, the influence of the GSTM1 allele variant genotype on GSTM1-mRNA quantity in oral squamous cell carcinoma (OSCC) and normal mucosa as well as the impact on prognosis remains unclear. The genotype for GSTM1 (mutation vs. wild type) was determined by polymerase chain reaction (PCR) using genomic DNA extracted from peripheral blood from 28 OSCC patients. From the same patients, 28 pairs of OSCC cells and normal oral mucosal cells were obtained by brush biopsy. mRNA was extracted from these paired samples and the expression levels of GSTM1 were examined by real-time reverse transcriptase qPCR (RT-qPCR). The mRNA expression of the OSCC samples was normalized against an external standard, as well as to the corresponding normal mucosa. The coincidence of GSTM1 genotype and GSTM1-mRNA-expression level was examined. In 15 patients (54%), the null genotype GSTM1 was present. In the GSTM1-null allele group, the GSTM1 gene expression level was determined at 1.63 (mean: 3.08; SD 3.4) folds vs. 3.6 (mean: 10.5; SD 14.2) folds in the group with the positive genotype (p=0.06), if calibrated vs. individual normal mucosa. More T3 and T4 OSCCs (+38%), higher UICC stadia (+38%) and more lymphatic metastasis (+28%) were seen in the group with the negative allele. Furthermore, positive GSTM1 genotype and enhanced GSTM1 gene expression was accompanied with increased tumor size, lymphatic metastasis status and UICC stadium. A coincidence of null type GSTM1 and lowered GSTM1 gene expression was observed. The larger tumors and more frequent lymph node metastases in this group could be explained by the insufficient cell protection by GST.

  18. Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

    Directory of Open Access Journals (Sweden)

    Marija G Matic

    Full Text Available OBJECTIVE: We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. PATIENTS AND METHODS: A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR with corresponding 95% confidence interval (95%CI was calculated. RESULTS: The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032. The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001. The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001. The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002. Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067. CONCLUSION: Null or low-activity genotypes of the

  19. Nostocyclopeptide-M1: a potent, nontoxic inhibitor of the hepatocyte drug transporters OATP1B3 and OATP1B1.

    Science.gov (United States)

    Herfindal, Lars; Myhren, Lene; Kleppe, Rune; Krakstad, Camilla; Selheim, Frode; Jokela, Jouni; Sivonen, Kaarina; Døskeland, Stein O

    2011-04-01

    We have isolated a novel cyanobacterial cyclic peptide (nostocyclopeptide M1; Ncp-M1) that blocks the hepatotoxic action of microcystin (MC) and nodularin (Nod). We show here that Ncp-M1 is nontoxic to primary hepatocytes in long-term culture. Ncp-M1 does not affect any known intracellular targets or pathways involved in MC action, like protein phosphatases, CaM-KII, or ROS-dependent cell death effectors. In support of this conclusion Ncp-M1 had no protective effect when microinjected into cells. Rather, the antitoxin effect was solely due to blocked hepatocyte uptake of MC and Nod. The hepatic uptake of MC and Nod is mainly via the closely related organic anion transporters OATP1B1 and OATP1B3, which also mediate hepatic transport of endogenous metabolites and hormones as well as drugs. OATP1B3 is also expressed in some aggressive cancers, where it confers apoptosis resistance. We show that Ncp-M1 inhibits transport through OATP1B3 and OATP1B1 expressed in HEK293 cells. The Ncp-M1 molecule has several nonproteinogenic amino acids and an imino bond, which hamper its synthesis. Moreover, a cyclic all L-amino acid heptapeptide analogue of Ncp-M1 also inhibits the OATP1B1/1B3 transporters, and with higher OATP1B3 preference than Ncp-M1 itself. The nontoxic Ncp-M1 and its synthetic cyclic peptide analogues thus provide new tools to probe the role of OATB1B1/1B3 mediated drug and metabolite transport in liver and cancer cells. They can also serve as scaffolds to design new, exopeptidase resistant OATP1B3-specific modulators.

  20. Experimental Conditions: SE37_S19_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S19 PSEUDO: Unlabeled and labeled Medicago samples for flavonoid annotation using ShiftedIonsFinde...03_M1) and for a blank sample (S16_M1 to S16_M3) are used. Import file name is unlabeling SE37_DS5 Flavonoid like peak search by ShiftedIonsFinder ...

  1. Radioiodinated ganglioside G/sub M1/: A potential tracer for neurological studies

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R.; Gallagher, P.; Magistretti, P.L.; Ghidoni, R.

    1985-05-01

    Ganglioside G/sub M1/ is a glycosphingolipid which appears to be involved in the regeneration of damaged neuronal tissue. In addition, it is being investigated clinically in the treatment of various neuropathies. If labeled with the appropriate isotope, G/sub M1/ might be useful as a probe of these processes, particularly if it accumulates preferentially in cerebral infarcts. The G/sub M1/ -tyr derivative was labeled with I-125 in 75% yield using the Iodogen method and at micellar concentration was isolated using gel chromatography. Binding of I-125 (G/sub M1/ -tyr) to rat neuronal membranes was measured at concentrations of 5,50, and 500 nM. The amount bound (8,26, and 158 pmol/gm membrane) was similar to that reported for H-3(G/sub M1/). The biodistribution of I-125(G/sub M1/ -tyr) in mice at both micellar and monomeric concentrations was also similar to that of H-3(G/sub M1/). However, at monomeric concentrations, thyroid uptake of I-125 was about 10 times higher than at micellar concentrations, suggesting differential dehalogenation of the two forms. Initial studies in the gerbil stroke model suggest that the uptake of I-125(G/sub M1/ -tyr) in damaged brain is twice that in normal tissue.

  2. CONDITIONAL INVOLVEMENT OF MUSCARINIC M(1) RECEPTORS IN VAGALLY MEDIATED CONTRACTION OF GUINEA-PIG BRONCHI

    NARCIS (Netherlands)

    TENBERGE, REJ; ROFFEL, AF; ZAAGSMA, J

    The involvement of ganglionic muscarinic M(1) receptors in vagally induced bronchoconstriction in guinea-pig airways is controversial. Therefore, we studied the effects of the M(1)-selective muscarinic receptor antagonist pirenzepine on vagus nerve (VNS, preganglionic) and electrical field

  3. A note on predicting recessions in the euro area using real M1

    OpenAIRE

    Jens Boysen-Hogrefe

    2012-01-01

    Real M1 is a renowned leading indicator used to forecast real economic activity. This note provides evidence that real M1 is also a suitable recession indicator that gave a clear and early signal for the Great Recession as long as changes in money demand are controlled for.

  4. Analytical Method (M): SE37_S18_M1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE37_S18_M1 This is a pseudo metadata prepared for integrated analyses of multiple ...datasets. The raw data obtained from LC-Orbitarp MS analyses for Medicago samples and a blank sample (S17_M1

  5. 12 CFR Appendix M1 to Part 226 - Generic Repayment Estimates

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Generic Repayment Estimates M1 Appendix M1 to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... rounded down to the nearest whole year if the estimate contains a fractional year less than 0.5,...

  6. Experimental Conditions: SE19_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE19_S2_M1_D1 SE19 Grobal triacylglycerol analysis in mouse liver and white adipose... tissue (WAT) by high resolution LC/ESI-QTOF MS/MS SE19_S2 Mouse white adipose tissue (WAT) SE19_S2_M1 20 ug

  7. FoxM1 is required for execution of the mitotic programme and chromosome stability

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Brás, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, H.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  8. FoxM1 is required for execution of the mitotic programme and chromosome stability.

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Bras, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, J.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  9. Nanometre-accurate form measurement machine for E-ELT M1 segments

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.

    2015-01-01

    To enable important scientific discoveries, ESO has defined a new ground-based telescope: the European Extremely Large Telescope (E-ELT). The baseline design features a telescope with a 39-m-class primary mirror (M1), making it the largest and most powerful telescope in the world. The M1 consists of

  10. Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ehlert, F.J.; Tran, L.P. (Univ. of California, Irvine (USA))

    1990-12-01

    The distribution of subtypes of the muscarinic receptor in homogenates of the rat brain was investigated by measuring the competitive inhibition of the binding (3H)N-methylscopolamine by pirenzepine and AF-DX 116 (11((2-((diethylamino)methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one). In most brain regions, the competitive binding curves for AF-DX 116 and pirenzepine were consistent with a two-site model. The dissociation constant of pirenzepine for its high-affinity site (M1 receptor) was approximately 10(-8) M, whereas the dissociation constant of AF-DX 116 for its high affinity site (M2 receptor) was approximately 10(-7) M. In many regions, particularly those in the forebrain, the sum of the densities of the M1 and M2 binding sites was substantially less than 100% of the total sites, indicating the existence of a third population of sites lacking high affinity for both pirenzepine and AF-DX 116. We have designated these latter sites as non-M1, non-M2 muscarinic receptors. In general, the densities of the M1 and non-M1, non-M2 binding sites were highest in cerebral cortex, corpus striatum and hippocampus, intermediate in thalamus and hypothalamus, and lowest in midbrain, medulla-pons and cerebellum, whereas the M2 binding site had a relatively low, uniform density throughout the brain. The binding capacity of (3H)N-methylquinuclidinyl benzilate was estimated to be 20 to 30% lower than that of (3H)quinuclidinyl benzilate in various regions of the forebrain, but not in more caudal regions of the brain where the two radioligands had approximately the same binding capacities.

  11. The luminosity function of cluster galaxies relations among M$_{1}$, M* and the morphological type

    CERN Document Server

    Trevese, D; Appodia, B

    1996-01-01

    A study of the luminosity function of 36 Abell clusters of galaxies has been carried out using photographic plates obtained with the Palomar 1.2 m Schmidt telescope. The relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M* has been analyzed. A positive correlation between M* and M_1 is found. However clusters appear segregated in the M_1-M* plane according to their Rood & Sastry class in such a way that on average M_1 becomes brighter while M* becomes fainter going from late to early Rood & Sastry and also Bautz & Morgan classes. Also a partial correlation analysis involving the magnitude M_10 of the 10th brightest galaxy, shows a negative intrinsic correlation between M_1 and M*. These results agree with the cannibalism model for the formation of brightest cluster members, and provide new constraints for theories of cluster formation and evolution.

  12. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Directory of Open Access Journals (Sweden)

    Yen-Po Chen

    Full Text Available Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8 CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  13. Cytological Effects of Space Environment on Different Genotype of Rice

    Institute of Scientific and Technical Information of China (English)

    WEI Li-jun; QIAN Yu; YANG Qian; XU Jian-long; WANG Jun-min; SUN Ye-qing

    2007-01-01

    For exploring the biological effect of space environment on different genotype of rice seeds, the cytological effects of M1 generation after space flight were studied.Twelve different genotypes of rice seeds which belong to different climate ecotype (early, medium and late) of indica and japonica were onboard "Shenzhou 4" spaceship for 162 h.After recovered the total number of mitosis cells and chromosomal aberration were observed.In all the lines the mitotic index (MIs) of space flight are much higher than control, which indicates the stimulate effect of space environment.The cell rate of chromosomal aberration (CRCA) of space flight is also much higher than control, but varies from line to line.It indicates that biological effect of space environment on rice seed dependents not only on flight duration but also on rice genotype.The radiosensitivities of different lines were also discussed according to CRCAs.

  14. Proteínas del gluten y reología de trigos harineros mexicanos influeciados por factores ambientales y genotípicos Gluten proteins and rheology of Mexican bread wheats as affected by environmental and genotypic factors

    Directory of Open Access Journals (Sweden)

    Micaela De la O Olán

    2010-09-01

    Full Text Available El objetivo de este estudio fue conocer el efecto de factores ambientales y genotípicos sobre los parámetros de calidad industrial y sobre la cantidad y relación de proteínas monoméricas y poliméricas del gluten en 24 líneas recombinantes de trigos harineros de temporal. El cultivo se desarrolló en cinco condiciones ambientales generadas por manejo agronómico, ciclo otoño-invierno 2006/2007, en Roque, Guanajuato, México. Se evaluaron el tiempo de amasado (TMA, fuerza (ALVW, extensibilidad (ALVPL de la masa, fracción rica en gliadina (50PS y en glutenina (50PI, y su relación (50PS/50PI. Las mejores combinaciones de gluteninas de alto y bajo peso molecular para TMA y ALVW fueron los genotipos con 1, 17+18, 5+10/Glu-A3c, Glu-B3g, Glu-D3b; 1, 17+18, 5+10/Glu-A3c, Glu-B3h, Glu-D3b, y 2*, 17+18, 5+10/Glu-A3c, Glu-B3g, Glu-D3b; para ALVPL, 2*, 17+18, 2+12/Glu-A3e, Glu-B3h, Glu-D3b; para 50PS, 2*, 17+18, 2+12/Glu-A3e, Glu-B3h, Glu-D3b; y 1, 17+18, 5+10/Glu-A3e, Glu-B3h, Glu-D3b. La relación 50PS/50PI fue mayor en genotipos con 2*, 17+18, 2+12/Glu-A3e, Glu-B3g, Glu-D3b. El TMA es mayor cuando aumenta la temperatura y la mejor ALVPL se obtiene en el ambiente bajo condiciones normales. La fracción 50PS y la relación 50PS/50PI son mayores cuando se realiza la fertilización con azufre, y se obtiene incremento de 50PI con riego limitado y aumento de temperaturas durante el llenado de grano.The objective of this study was to determine the effect of environmental and genotypic factors on industrial quality and on the monomeric and polymeric protein contents and ratio of 24 rainfed bread wheat recombinant lines. The cultivation was done in five environmental conditions generated by agronomic management in the autumn-winter 2006/2007 cycle, at Roque, Guanajuato, Mexico. The mixing time (TMA, strength (ALVW and extensibility (ALVPL of the dough, gliadin (50PS and glutenin (50PI rich fractions, and their ratio (50PS/50PI, were evaluated. The best

  15. Exploration of FoxM1 and downstream related target molecule expression in cervical cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Yi-Chong Yuan; QiongYang

    2016-01-01

    Objective:To study the expression of FoxM1 and downstream related target molecules in cervical cancer tissue.Methods:Cervical cancer tissue and normal cervical tissue were collected to detect the expression of FoxM1, proliferation-related genes (CDK6 and CDK8) and angiogenesis-related genes (VEGFA, VEGFB and VEGFC); Hela cells were cultured and transfected with FoxM1 siRNA, and then expression of CDK6, CDK8, VEGFA, VEGFB and VEGFC were detected.Results:mRNA contents of FoxM1, CDK6, CDK8, VEGFA, VEGFB and VEGFC in cervical cancer tissue were significantly higher than those in normal cervical tissue; mRNA content of FoxM1 was positively correlated with mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC; mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC of FoxM1-siRNA group were significantly lower than those of negative control-siRNA group.Conclusion:FoxM1 expression abnormally increases in cervical cancer tissue, and its downstream target genes include CDK6, CDK8, VEGFA, VEGFB and VEGFC.

  16. Emergence and oscillation of cosmic space by joining M1-branes

    CERN Document Server

    Sepehri, Alireza; Capozziello, Salvatore; Ali, Ahmed Farag; Pradhan, Anirudh

    2016-01-01

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises, how this model could explain the oscillation of universe between contraction and expansion branches? We try to address this issue in the framework of BIonic system. In this model, $M0$-branes join to each other and give rise to a pair of $M1$-anti-$M1$-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of $M1$ and the bulk leading to an expansion of $M1$-branes. When $M1$-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To removes these states, $M1$...

  17. Pattern and molecular epidemiology of Hepatitis B virus genotypes circulating in Pakistan.

    Science.gov (United States)

    Awan, Zunaira; Idrees, Muhammad; Amin, Irum; Butt, Sadia; Afzal, Samia; Akbar, Haji; Rehman, Irshad-ur; Younas, Saima; Shahid, Muhammad; Lal, Amreek; Saleem, Sana; Rauff, Bisma

    2010-12-01

    The continuously mutating nature of Hepatitis B virus (HBV) is responsible for the emergence of varying genotypes in different regions of the world affecting the disease outcome. The objective of the current study was to find out the pattern of HBV genotypes circulating in Pakistan. HBV genotypes were determined in HBV chronic patients of different age and gender from all the four different geographical regions (provinces) of Pakistan for a period of 2 years (2007-2009). Out of the total 3137 consecutive patients, 300 (175; 58.3% males and 125; 41.7% females) were randomly selected for HBV genotype A through H determination using molecular genotyping methods. Total 269 (89.6%) isolates were successfully genotyped where as 31 (10.3%) samples failed to generate a type-specific PCR band and were found untypable. Out of the successfully genotyped samples, 43 (14.3%) were with type A, 54 (18%) were with type B, 83 (27.6%) were with type C, 39 (13%) were with type D, 2 (0.6%) were with type E, 4 (1.3%) were with genotype F and total 44 (14.6%) were with mixed HBV infections. Of the mixed genotype infection cases, 16 were with genotypes A/D, 9 were B/C, six were A/D/F, five were with genotypes A/F, two were with A/B/D and B/E and one each for A/C as well as A/E genotypes. Four common genotypes of HBV found worldwide (A, B, C & D) were isolated from Pakistan along with uncommon genotypes E and F for the first time in Pakistan. Overall Genotype C is the most prevalent genotype. Genotypes B and C are predominant in Punjab & Balochistan and Khyber Pakhtoonkhwa, respectively whereas genotype A in Sindh.

  18. The role of glutathione S-transferase M1 and T1 gene polymorphisms and fruit and vegetable consumption in antioxidant parameters in healthy subjects.

    Science.gov (United States)

    Yuan, Lin-Hong; Meng, Li-Ping; Ma, Wei-Wei; Li, Sheng; Feng, Jin-Fang; Yu, Huan-Ling; Xiao, Rong

    2012-03-01

    The correlation of glutathione S-transferase (GST) M1/T1 genetic polymorphisms with oxidative stress-related chronic diseases was proved recently. The aim of the present study was to investigate the association of GSTM1/T1 genetic polymorphisms with antioxidant biomarkers and consumption of fruits and vegetables (F&V) in healthy subjects. In this study, for conducting a 3 d dietary survey, 190 healthy adults were recruited. After DNA extraction, a multiple PCR method was used for GSTM1/T1 genotyping. A spectrophotometer method was applied for the determination of plasma total antioxidant capacity (T-AOC), vitamin C level and erythrocyte GST enzyme activity. A general linear model was used to compare the mean values of antioxidant parameters for different GSTM1/T1 genotypes and consumption of F&V. Polymorphisms of GSTM1/T1 had no effects on plasma T-AOC and vitamin C levels. Deletion of the GSTM1 gene decreased the erythrocyte GST activity. There was correlation between plasma T-AOC and consumption of F&V in the GSTM1⁻ or GSTT1⁺ subjects. A similar pattern was evident for erythrocyte GST activity in the GSTM1⁻ subjects. No association was found among consumption of F&V and GSTM1/T1 genotypes and plasma vitamin C level. Different consumption of F&V had no impact on plasma T-AOC and vitamin C levels in the GSTM1⁻/GSTT1⁺ or GSTM1⁻/GSTT1⁻ subjects. The erythrocyte GST activity was more sensitive to consumption of F&V in the individuals with the GSTM1⁻/GSTT1⁺ genotype. Association was found among GSTM1/T1 genotypes, antioxidant parameters and consumption of F&V. Large-scale and multiple ethnic studies are needed to further evaluate the relationship.

  19. Enzyme-linked immunosorbent assay for determination of aflatoxin M1 based on magnetic nanoparticles

    Science.gov (United States)

    Atanasova, M. K.; Ivanova, N. V.; Godjevargova, T. I.

    2017-02-01

    A sensitive enzyme immunoassay with magnetic nanoparticles (Method A) for the quantitative determination of aflatoxin M1 in milk was developed. This immunoassay was based on the immobilization of monoclonal antibody (mAb) on the modified magnetic nanoparticles (MNPs-NH2). It was observed that for each mg of the MNPs, 25 µg of antibody was immobilized. Both aflatoxin M1 in the sample and aflatoxin M1-BSA-peroxidase conjugate competed for the immobilized antibody. The proposed Method A was compared with other method (B). The Method B was based on the immobilization of aflatoxin M1-BSA conjugate on the MNPs-NH2, which competed with the aflatoxin M1 in the sample for binding to the added mAb. The binding of mAb to the aflatoxin M1-BSA-MNPs-NH2 was detected using a target secondary IgG-peroxidase antibody. The analytical characteristics of the two methods were compared. Real milk samples were investigated for present of aflatoxin M1. Two methods were based on the use of MNPs as a solid support for covalently immunoreagents immobilization. A comfortable separation of bound and free fraction of the tracer can be performed only through a simple collection of the MNPs by a permanent magnet. The application of MNPs helps to eliminate non-specific binding and to retain higher activity of bound biomolecules. The development of a MNPs-based ELISA for determination of aflatoxin M1 has a great potential to supersede the traditional ELISA for aflatoxin M1 diagnosis.

  20. Genotype × Environment Interaction for Iron Concentration of Rice in Central Java of Indonesia

    Institute of Scientific and Technical Information of China (English)

    Suwarto; Nasrullah

    2011-01-01

    To explore the effect of genotype and genotype × environment interaction on Fe concentration in rice grains,Fe concentrations of 10 genotypes were analyzed across eight paddy field environments during 2007-2008 using the AMMI-biplot method.Experiments were conducted using a randomized completely block design with three replications in eight environments.Results indicated that environment (E),genotype (G) and genotype × environment interaction (GE) significantly affected Fe concentration in rice grains.Environment explained 74.43 % of total (G+E+GE) variation,whereas G and GE captured 5.60% and 19.67%,respectively.Rice genotype Barumun was desirable in terms of the highest ability and stability for Fe concentration in rice grains.Environment in genotype Cilongok was the best representative of the overall environments and the most powerful to discriminate rice genotypes.

  1. Bounds on Subspace Codes Based on Subspaces of Type (m,1 in Singular Linear Space

    Directory of Open Access Journals (Sweden)

    You Gao

    2014-01-01

    Full Text Available The Sphere-packing bound, Singleton bound, Wang-Xing-Safavi-Naini bound, Johnson bound, and Gilbert-Varshamov bound on the subspace codes n+l,M,d,(m,1q based on subspaces of type (m,1 in singular linear space Fq(n+l over finite fields Fq are presented. Then, we prove that codes based on subspaces of type (m,1 in singular linear space attain the Wang-Xing-Safavi-Naini bound if and only if they are certain Steiner structures in Fq(n+l.

  2. Visible Genotype Sensor Array

    Directory of Open Access Journals (Sweden)

    Takashi Imai

    2008-04-01

    Full Text Available A visible sensor array system for simultaneous multiple SNP genotyping has been developed using a new plastic base with specific surface chemistry. Discrimination of SNP alleles is carried out by an allele-specific extension reaction using immobilized oligonucleotide primers. The 3’-ends of oligonucleotide primers are modified with a locked nucleic acid to enhance their efficiency in allelic discrimination. Biotin-dUTPs included in the reaction mixture are selectively incorporated into extending primer sequences and are utilized as tags for alkaline phosphatase-mediated precipitation of colored chemical substrates onto the surface of the plastic base. The visible precipitates allow immediate inspection of typing results by the naked eye and easy recording by a digital camera equipped on a commercial mobile phone. Up to four individuals can be analyzed on a single sensor array and multiple sensor arrays can be handled in a single operation. All of the reactions can be performed within one hour using conventional laboratory instruments. This visible genotype sensor array is suitable for “focused genomics” that follows “comprehensive genomics”.

  3. The Hotspot for (Global) One Health in Primary Food Production: Aflatoxin M1 in Dairy Products.

    Science.gov (United States)

    Frazzoli, Chiara; Gherardi, Paola; Saxena, Navneet; Belluzzi, Giancarlo; Mantovani, Alberto

    2016-01-01

    One Health involves the multifaceted environment-animal-human web: nevertheless, the role of toxicological issues has yet to be fully explored in this context. Aflatoxin B1 (AFB1) contamination of feeds is a risk for the health of several farm animals, including fishes; milk is the only food of animal origin where a significant feed-food carry over may occur. The main AFB1-related compound present in milk is the hydroxy-metabolite aflatoxin M1 (AFM1). Besides contamination of raw milk, AFM1 is of concern for the whole dairy chain; AFM1 may also contaminate the milk of several other ruminants used for milk/dairy production. In a One Health perspective, milk represents a sentinel matrix for AFB1 vulnerability of the agro-food system, that is crucial in a phase when food/nutritional security becomes a global issue and climatic changes may affect agricultural productions. In the global setting, food chain exposure to long-term toxicants, such as AFM1, is a growing concern for economically developing countries, whereas global trade and climatic change makes AFM1 an emerging hot issue in economically developed countries as well. We critically review the state of the art on AFM1 risk assessment and risk management using two scenarios as case studies: a European Union country where the health system aims at ensuring a high-level protection of food chain (Italy) and the world's largest (and economically developing) producer of dairy products by volume (India). The case studies are used to provide building blocks for a global One Health framework.

  4. Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy

    Directory of Open Access Journals (Sweden)

    Wang Yujuan

    2012-11-01

    Full Text Available Abstract Background Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy. Case presentation We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively

  5. Absence of a significant linkage between Na(+),K(+)-ATPase subunit (ATP1A3 and ATP1B3) genotypes and bipolar affective disorder in the old-order Amish.

    Science.gov (United States)

    Philibert, R A; Cheung, D; Welsh, N; Damschroder-Williams, P; Thiel, B; Ginns, E I; Gershenfeld, H K

    2001-04-08

    Previous studies provide evidence for a genetic component for susceptibility to bipolar affective disorder (BPAD) in the old-order Amish population. El-Mallakh and Wyatt [1995: Biol Psychiatry 37:235-244] have suggested that the Na(+),K(+)-ATPase may be a candidate gene for BPAD. This study examines the relationship between BPAD in the old-order Amish cohort and the Na(+),K(+)-ATPase alpha1 and beta3 subunit genes (ATP1A3, ATP1B3). A total of 166 sibling pairs were analyzed for linkage via nonparametric methods. Suggestive levels of statistical significance were not reached in any stratification model for affective illness. Overall, the results do not support linkage of bipolar disorder to the Na(+),K(+)-ATPase alpha subunit gene (ATP1A3) and beta subunit gene (ATP1B3) in these old-order Amish families and they show that these Na(+),K(+)-ATPase subunit genes are not major effect genes (>or=fourfold increased genetic risk of disease) for BPAD in the old-order Amish pedigrees. We cannot exclude other genetic variants of the Na(+),K(+)-ATPase hypothesis for BPAD, whereby other loci may modifying Na(+),K(+)-ATPase activity. Copyright 2001 Wiley-Liss, Inc.

  6. Locations of All Shotpoints, USGS Cruise M1-98-GM (GOM98SHTALLG.SHP)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — All shotpoint locations from multichannel seismics survey, USGS cruise M1-98-GM. During June 1998 and April 1999, the U.S. Geological Survey (USGS) conducted two...

  7. Aflatoxin M1 levels in raw milk, pasteurized milk and infant formula

    National Research Council Canada - National Science Library

    Omar, Sharaf Shareef

    2016-01-01

    The incidence of contamination of aflatoxin M1 (AFM1) in milk samples collected from the Jordanian market was investigated by using the competitive enzyme linked immunosorbent assay (ELISA) technique...

  8. Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

  9. Towards Revised Step IV MICE Optics in the Absence of M1 SSD

    Energy Technology Data Exchange (ETDEWEB)

    Bayes, R. [Univ. of Glasgow, Scotland (United Kingdom); Berg, J. S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blackmore, V. [Imperial College, London (United Kingdom); Hunt, C. [Imperial College, London (United Kingdom); Liu, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pasternak, J. [Imperial College, London (United Kingdom); Rogers, C. T. [Science and Technology Facilities Council (STFC), Oxford (United Kingdom). Rutherford Appleton Lab. (RAL)

    2015-10-01

    During magnet commissioning in September 2015, the leads on coil M1 of the downstream spectrometer solenoid failed. The coil will not be operational for MICE Step IV. Revised optics settings for the Step IV data taking are reviewed.

  10. Coiled-Coil Irregularities and Instabilities in Group A Streptococcus M1 Are Required for Virulence

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Case; Zinkernagel, Annelies S.; Macheboeuf, Pauline; Cunningham, Madeleine W.; Nizet, Victor; Ghosh, Partho (UO-HSC); (UCSD)

    2008-07-21

    Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the -3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.

  11. Presence of Aflatoxin M1 in Raw Milk for Human Consumption in Palestinian

    Directory of Open Access Journals (Sweden)

    Ibrahim Mahmoud AL ZUHEIR

    2012-09-01

    Full Text Available The absences or insufficient food control program result in the occurrence of mycotoxin in milk and milk products, which poses a serious risk for humans and can be a public health concern. This study was conducted to highlight the occurrence of aflatoxin M1 in Palestine raw milk collected at farms from Tulkarm, Nablus and Jenin. Aflatoxin M1 was determined by direct competitive ELISA technique. 85 % (34 of 40 of the total examined raw milk samples tested were positive. The aflatoxin M1 contamination levels were between 3 - 80 ppt with a mean of 29.57 ppt. There was a high incidence rate with 92 % (11 of 12 and the highest means of contaminated with aflatoxin M1 in the samples tested in Tulkarm city (P ≤ 0.05. 20 % of the analyzed samples (8 of 40 exceeded the maximum permissible limit (50 ppt in European Codex, with a range of 2 - 80 ppt.

  12. Bion M1. Peculiarities of life activities of microbes in 30-day spaceflight

    Science.gov (United States)

    Viacheslav, Ilyin; Korshunov, Denis; Morozova, Julia; Voeikova, Tatiana; Tyaglov, Boris; Novikova, Liudmila; Krestyanova, Irina; Emelyanova, Lydia

    The aim of this work was to analyze the influence of space flight factors ( SFF) to microorganism strains , exposed inside unmanned spacecraft Bion M-1 during the 30- day space flight. Objectives of the work - the study of the influence of the SFF exchange chromosomal DNA in crosses microorganisms of the genus Streptomyces; the level of spontaneous phage induction of lysogenic strains fS31 from Streptomyces lividans 66 and Streptomyces coelicolor A3 ( 2 ) on the biosynthesis of the antibiotic tylosin strain of Streptomyces fradiae; survival electrogenic bacteria Shewanella oneidensis MR- 1 is used in the microbial fuel cell As a result of this work it was found that the SFF affect the exchange of chromosomal DNA by crossing strains of Streptomyces. Was detected polarity crossing , expressed in an advantageous contribution chromosome fragment of one of the parent strains in recombinant offspring. This fact may indicate a more prolonged exposure of cells in microgravity and , as a consequence, the transfer of longer fragments of chromosomal DNA This feature is the transfer of genetic material in microgravity could lead to wider dissemination and horizontal transfer of chromosomal and plasmid DNA of symbiotic microflora astronauts and other strains present in the spacecraft. It was shown no effect on the frequency of recombination PCF and the level of mutation model reversion of auxotrophic markers to prototrophy It was demonstrated that PCF increase the level of induction of cell actinophage fS31 lysogenic strain of S. lividans 66, but did not affect the level of induction of this phage cells S. coelicolor A3 ( 2). It is shown that the lower the level of synthesis PCF antibiotic aktinorodina (actinorhodin) in lysogenic strain S. coelicolor A3 ( 2). 66 Strains of S. lividans and S. coelicolor A3 ( 2 ) can be used as a biosensor for studying the effect on microorganisms PCF It is shown that the effect of the PCF reduces synthesis of tylosin and desmicosyn S. fradiae at

  13. FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Nuo XU; Xin ZHANG; Xun WANG; Hai-yan GE; Xiao-ying WANG; David GARFIELD; Ping YANG; Yuan-lin SONG; Chun-xue BAI

    2012-01-01

    Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC),and the underlying mechanism remains unclear.FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients.In this study,we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms.Methods:Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used.mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis.RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells,and lentiviral infection was used to overexpress FoxM1 in H292 cells.MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells.Results:Treatment of SPC-A-1 cells with gefitinib (1 and 10 μmol/L) upregulated the expression of FoxM1 in time- and concentrationdependent manners,while gefrtinib (1 μmol/L) downregulated in H292 cells.In SPC-A-1 cells treated with gefitinib (1 μmol/L),the expression of several downstream targets of FoxM1,including survivin,cyclin B1,SKP2,PLK1,Aurora B kinase and CDC25B,were significantly upregulated.Overexpression of FoxM1 increased the resistance in H292 cells,while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis.Conclusion:The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro.FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

  14. q-differential operator representation of the quantum superalgebra Uq(sl(M+1|N+1))

    CERN Document Server

    Kimura, K

    1996-01-01

    A representation of the quantum superalgebra Uq(sl(M+1|N+1)) is constructed based on the q-differential operators acting on the coherent states parameterized by coordinates. These coordinates correspond to the local ones of the flag manifold. This realization provides us with a guide to construct the free field realization for the quantum affine superalgebra Uq^(sl(M+1|N+1)) at arbitrary level.

  15. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

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    R. Kazemi Darsanaki

    2013-11-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  16. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2014-05-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  17. The Evaluation of Aflatoxin M1 Level in Collected Raw Milk for Pasteurized Dairy

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    Ehsan Sadeghi

    2013-03-01

    Full Text Available Background: Aflatoxins are fungal toxins that have carcinogenic, cellular mutations and malformation effects. Aflatoxin M1 resists pasteurization, autoclave and the other methods that make foodstuff healthy. This study aims to determine the contents of aflatoxin M1 in raw milk of milk factories in Kermanshah province.Materials and Methods: This research is carried out through the descriptive-cross sectional method. Among the raw milk received by four pasteurized milk factories in Kermanshah, coded by (A, B, C, D labels, six samples, totally 320 samples (80 samples from each factory, were taken within four seasons. The concentration of aflatoxin M1 was examined by Enzyme-Linked Immunosorbent Assay (ELISA. The mean difference was analyzed statistically through t-test using SPSS software. Results: The content of aflatoxin was higher than Codex standard (0.5 µg/l in 295 samples. The total mean was 1.21, which exceeds two times the Codex standard. The highest and lowest contents of aflatoxin M1 were observed in “Factory D” in spring and in “Factory A” in autumn, respectively. There was a significant difference between contamination of aflatoxin M1 and different seasons (p< 0.05.Conclusion: High content of aflatoxin M1 in raw milk is worrying. Measuring the content of aflatoxin M1 is essential to reduce the toxin entering the daily food of animals and the other related factors. The considerable difference of aflatoxin M1 content between Factory D and Factory A can be attributed to the amount of the local milk and the industrial milk received by the factories.

  18. Emergence and oscillation of cosmic space by joining M1-branes

    Energy Technology Data Exchange (ETDEWEB)

    Sepehri, Alireza [Shahid Bahonar University, Faculty of Physics, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Rahaman, Farook [Jadavpur University, Department of Mathematics, Kolkata, West Bengal (India); Capozziello, Salvatore [Universita di Napoli Federico II, Dipartimento di Fisica ' ' E. Pancini' ' , Naples (Italy); Gran Sasso Science Institute (INFN), L' Aquila (Italy); Tomsk State Pedagogical University, Tomsk (Russian Federation); INFN Sezione di Napoli, Naples (Italy); Ali, Ahmed Farag [Benha University, Department of Physics, Faculty of Science, Benha (Egypt); Pradhan, Anirudh [G L A University, Department of Mathematics, Institute of Applied Sciences and Humanities, Mathura, Uttar Pradesh (India)

    2016-05-15

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  19. Emergence and oscillation of cosmic space by joining M1-branes

    Science.gov (United States)

    Sepehri, Alireza; Rahaman, Farook; Capozziello, Salvatore; Ali, Ahmed Farag; Pradhan, Anirudh

    2016-05-01

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti- M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti- M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands.

  20. Optical illusion alters M1 excitability after mirror therapy: a TMS study.

    Science.gov (United States)

    Läppchen, C H; Ringer, T; Blessin, J; Seidel, G; Grieshammer, S; Lange, R; Hamzei, F

    2012-11-01

    The contralesional primary motor cortex (M1) has been suggested to be involved in the motor recovery after mirror therapy, but whether the ipsilesional M1 is influenced by the contralesional M1 via transcallosal interhemispheric inhibition (IHI) is still unclear. The present study investigated the change of IHI as well as the intracortical inhibition and intracortical facilitation of both M1 induced by training in a mirror with the use of transcranial magnetic stimulation (TMS). In this 2 × 2 factorial design (time × group), healthy subjects exercised standardized motor skills with their right hand on four consecutive days. Either a mirror (mirror group) or a board (control group) was positioned between their hands. Before and after training TMS was applied along with training tests of both hands. Tests were the same motor skills exercised daily by both groups. Tests of the untrained left hand improved significantly more in the mirror group than in the control group after training (P = 0.02) and showed a close correlation with an increase of intracortical inhibition of M1(left). IHI did not show any difference between investigation time points and groups. The present study confirms the previous suggestion of the involvement of the "contralesional" left-side (ipsilateral to the hand behind the mirror) M1 after mirror therapy, which is not mediated by IHI. Even with the same motor skill training (both groups performed same motor skills) but with different visual information, different networks are involved in training-induced plasticity.

  1. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases.

    Science.gov (United States)

    Tang, Yu; Le, Weidong

    2016-03-01

    One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.

  2. STR MARKERS. GENOTYPING APPLICATIONS

    Directory of Open Access Journals (Sweden)

    I. O. Sirbu

    2001-01-01

    Full Text Available STR (short tandem repeats loci consist of short, repetitive sequence elements of 2-8 bp in length. These abundant repeats are well distributed throughout the human genome and are rich source of highly polymorphic markers. There are literally hundreds of STR systems which have been mapped throughout the human genome. Several dozen have been investigated for application to human identity testing. These STR loci are found on almost every chromosome in the genome. They may be amplified using a variety of PCR primers. Tetranucleotide repeats have been most popular among forensic scientists due to their fidelity in PCR amplification although some tri- and pentanucleotide repeats are also in use. In this paper we intend (far from being exhaustive to present a synthesis of the characteristics of these genetic markers and their applications in genotyping, giving as an example the use of the STRs in a paternity testing case.

  3. The influence of polymorphisms of glutathione S-transferases M1 and M3 on the development of human urothelial cancer.

    Science.gov (United States)

    Golka, Klaus; Schmidt, Tobias; Seidel, Thilo; Dietrich, Holger; Roemer, Hermann C; Lohlein, Dietrich; Reckwitz, Thomas; Sokeland, Jurgen; Weistenhofer, Wobbeke; Blaszkewicz, Meinolf; Selinski, Silvia

    2008-01-01

    Cigarette smoking is the most important risk factor for development of transitional cell carcinoma of the urinary bladder. The effect of polymorphisms of glutathione S-transferases M1 (GSTM1) and M3 (GSTM3) on the influence of cigarette smoking on urinary bladder carcinogenesis was investigated. In total, 293 bladder cancer patients from hospitals in Dortmund and Wittenberg as well as 176 patients without any malignancy from a Department of Surgery from Dortmund were genotyped for GSTM1 and GSTM3 according to standard PCR/RFLP methods. Smoking habits were quantified by a standardized interview. The proportion of GSTM1 negative cases was 63% in the entire bladder cancer cases group compared to 50% in controls. The GSTM3*A/*A genotype was 76% in cancer cases versus 74% in controls. Smokers and ex-smokers were overrepresented in bladder cancer cases. A significant association between smoking status and GSTM1 or GSTM3 genotype was not detected. The elevated proportion of GSTM1 negative bladder cancer cases shows an effect of this polymorphic enzyme on development of bladder cancer. In contrast to other studies, an influence of GSTM1 on the risk due to cigarette smoking was not observed.

  4. Plaque Size Is Decreased but M1 Macrophage Polarization and Rupture Related Metalloproteinase Expression Are Maintained after Deleting T-Bet in ApoE Null Mice.

    Directory of Open Access Journals (Sweden)

    Aikaterini Tsaousi

    Full Text Available Thelper1 (Th1 lymphocytes have been previously implicated in atherosclerotic plaque growth but their role in plaque vulnerability to rupture is less clear. We investigated whether T-bet knockout that prevents Th1 lymphocyte differentiation modulates classical (M1 macrophage activation or production of matrix degrading metalloproteinases (MMPs and their tissue inhibitors, TIMPs.We studied the effect of T-bet deletion in apolipoproteinE (ApoE knockout mice fed a high fat diet (HFD or normal chow diet (ND. Transcript levels of M1/M2 macrophage polarization markers, selected MMPs and TIMPs were measured by RT-qPCR in macrophages isolated from subcutaneous granulomas or in whole aortae. Immunohistochemistry of aortic sinus (AS and brachiocephalic artery (BCA plaques was conducted to quantify protein expression of the same factors. Deletion of T-bet decreased mRNA for the M1 marker NOS-2 in granuloma macrophages but levels of M2 markers (CD206, arginase-1 and Ym-1, MMPs-2, -9, -12, -13, -14 and -19 or TIMPs-1 to -3 were unchanged. No mRNA differences were observed in aortic extracts from mice fed a HFD for 12 weeks. Moreover, AS and BCA plaques were similarly sized between genotypes, and had similar areas stained for NOS-2, COX-2, MMP-12 and MMP-14 proteins. T-bet deletion increased MMP-13, MMP-14 and arginase-1 in AS plaques. After 35 weeks of ND, T-bet deletion reduced the size of AS and BCA plaques but there were no differences in the percentage areas stained for M1 or M2 markers, MMPs-12, -13, -14, or TIMP-3.Absence of Th1 lymphocytes is associated with reduced plaque size in ApoE knockout mice fed a normal but not high fat diet. In either case, M1 macrophage polarization and expression of several MMPs related to plaque instability are either maintained or increased.

  5. The Plasmodium falciparum malaria M1 alanyl aminopeptidase (PfA-M1: insights of catalytic mechanism and function from MD simulations.

    Directory of Open Access Journals (Sweden)

    Peter M Jones

    Full Text Available Malaria caused by several species of Plasmodium is major parasitic disease of humans, causing 1-3 million deaths worldwide annually. The widespread resistance of the human parasite to current drug therapies is of major concern making the identification of new drug targets urgent. While the parasite grows and multiplies inside the host erythrocyte it degrades the host cell hemoglobin and utilizes the released amino acids to synthesize its own proteins. The P. falciparum malarial M1 alanyl-aminopeptidase (PfA-M1 is an enzyme involved in the terminal stages of hemoglobin digestion and the generation of an amino acid pool within the parasite. The enzyme has been validated as a potential drug target since inhibitors of the enzyme block parasite growth in vitro and in vivo. In order to gain further understanding of this enzyme, molecular dynamics simulations using data from a recent crystal structure of PfA-M1 were performed. The results elucidate the pentahedral coordination of the catalytic Zn in these metallo-proteases and provide new insights into the roles of this cation and important active site residues in ligand binding and in the hydrolysis of the peptide bond. Based on the data, we propose a two-step catalytic mechanism, in which the conformation of the active site is altered between the Michaelis complex and the transition state. In addition, the simulations identify global changes in the protein in which conformational transitions in the catalytic domain are transmitted at the opening of the N-terminal 8 Å-long channel and at the opening of the 30 Å-long C-terminal internal chamber that facilitates entry of peptides to the active site and exit of released amino acids. The possible implications of these global changes with regard to enzyme function are discussed.

  6. Differences in ovarian aging patterns between races are associated with ovarian genotypes and sub-genotypes of the FMR1 gene

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    Gleicher Norbert

    2012-09-01

    Full Text Available Abstract Background Ovarian aging patterns differ between races, and appear to affect fertility treatment outcomes. What causes these differences is, however, unknown. Variations in ovarian aging patterns have recently been associated with specific ovarian genotypes and sub-genotypes of the FMR1 gene. We, therefore, attempted to determine differences in how functional ovarian reserve (FOR changes with advancing age between races, and whether changes are associated with differences in distribution of ovarian genotypes and sub-genotypes of the FMR1 gene. Methods We determined in association with in vitro fertilization (IVF FOR in 62 young Caucasian, African and Asian oocyte donors and 536 older infertility patients of all three races, based on follicle stimulating hormone (FSH, anti-Müllerian hormone (AMH and oocyte yields, and investigated whether differences between races are associated with differences in distribution of FMR1 genotypes and sub-genotypes. Results Changes in distribution of mean FSH, AMH and oocyte yields between young donors and older infertility patients were significant (all P FMR1 genotypes and sub-genotypes in patients varied significantly between races, with Asians demonstrating fewer het-norm/low sub-genotypes than Caucasians and Africans (P = 0.012. Conclusion FOR changes in different races at different rates, and appears to parallel ovarian FMR1 genotypes and sub-genotype distributions. Differences in ovarian aging between races may, therefore, be FMR1-associated.

  7. M1 contributes to the intrinsic but not the extrinsic components of motor-skills.

    Science.gov (United States)

    Romei, Vincenzo; Thut, Gregor; Ramos-Estebanez, Ciro; Pascual-Leone, Alvaro

    2009-10-01

    Procedural skills consist of several components that can be simultaneously acquired. During a motor-learning task we can distinguish between how a "movement" is performed (intrinsic component) and the spatial-related (extrinsic) component of this movement. The intrinsic movement component is thought to be supported by motor loops, including primary motor cortex (M1) as assessed with neuroimaging studies. Here we want to test further whether M1 makes a critical contribution to the movement rather than spatial-related component of skill-learning. To this purpose, we used repetitive Transcranial Magnetic Stimulation (rTMS) and the serial reaction time (SRT) task. Twenty right-handed participants performed the SRT-task starting with their left or right hand. After this learning session, participants switched to the untrained hand by performing original (spatial-related) and mirror-ordered (movement-based) sequences. rTMS was applied to M1 ipsi- or contralateral to the transfer-hand and both sequences were retested. Results revealed rTMS-interference with motor-skill transfer of mirror-ordered but not original sequences, showing that M1 is critically involved in the retrieval/transformation of the intrinsic but not the extrinsic movement coordinates. rTMS-interference in the mirror-condition consisted of both (i) disruption and (ii) release of motor-skill transfer depending on the stimulated hemisphere and on transfer-hand. The pattern of results suggests (i) contralateral (right) M1 involvement in retrieval/transformation of motor information during left-hand reproduction of previously acquired right-hand motor-skills; and (ii) modulatory interactions of inhibitory nature from the dominant (left) to the non-dominant (right) M1 in the same transfer-condition. These results provide further evidence that M1 is essential to intrinsic movement-based skill-learning and novel insight on models of motor-learning and hemispheric specialization, suggesting the involvement of

  8. Neoglycolipid analogues of ganglioside G sub M1 as functional receptors of cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Pacuszka, T.; Bradley, R.M.; Fishman, P.H. (National Inst. of Health, Bethesda, MD (United States))

    1991-03-12

    The authors synthesized several lipid analogues of ganglioside G{sub M1} by attaching its oligosaccharide moiety (G{sub M1}OS) to aminophospholipids, aliphatic amines, and cholesteryl hemisuccinate. They incubated G{sub M1}-deficient rat glioma C6 cells with each of the derivatives as well as native G{sub M1} and assayed the cells for their ability to bind and respond to cholera toxin. On the basis of the observed increase in binding of {sup 125}I-labeled cholera toxin, it was apparent that the cells took up and initially incorporated most of the derivatives into the plasma membrane. In the case of the aliphatic amine derivatives, the ability to generate new toxin binding sites was dependent on chain length; whereas the C{sub 10} derivative was ineffective, C{sub 12} and higher analogues were effective. Increased binding was dependent on both the concentration of the neoglycolipid in the medium and the time of exposure. Cells pretreated with the various derivatives accumulated cyclic AMP in response to cholera toxin, but there were differences in their effectiveness. The cholesterol and long-chain aliphatic amine derivatives were more effective than native G{sub M1}, whereas the phospholipid derivatives were less effective. The distance between G{sub M1}OS and the phospholipid also appeared to influence its functional activity. The results indicate that although G{sub M1}OS provides the recognition site for the binding of cholera toxin, the nature of the lipid moiety plays an important role in the action of the toxin.

  9. Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis.

    Science.gov (United States)

    Chen, Fang-Yuan; Zhou, Juan; Guo, Ning; Ma, Wang-Ge; Huang, Xin; Wang, Huan; Yuan, Zu-Yi

    2015-11-27

    Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect.

  10. Molecular characterization of the Hepatitis B virus genotypes in Colombia: a Bayesian inference on the genotype F.

    Science.gov (United States)

    Alvarado Mora, Mónica Viviana; Romano, Camila Malta; Gomes-Gouvêa, Michele Soares; Gutierrez, Maria Fernanda; Botelho, Livia; Carrilho, Flair José; Pinho, João Renato Rebello

    2011-01-01

    Hepatitis B is a worldwide health problem affecting about 2 billion people and more than 350 million are chronic carriers of the virus. Nine HBV genotypes (A to I) have been described. The geographical distribution of HBV genotypes is not completely understood due to the limited number of samples from some parts of the world. One such example is Colombia, in which few studies have described the HBV genotypes. In this study, we characterized HBV genotypes in 143 HBsAg-positive volunteer blood donors from Colombia. A fragment of 1306 bp partially comprising HBsAg and the DNA polymerase coding regions (S/POL) was amplified and sequenced. Bayesian phylogenetic analyses were conducted using the Markov Chain Monte Carlo (MCMC) approach to obtain the maximum clade credibility (MCC) tree using BEAST v.1.5.3. Of all samples, 68 were positive and 52 were successfully sequenced. Genotype F was the most prevalent in this population (77%) - subgenotypes F3 (75%) and F1b (2%). Genotype G (7.7%) and subgenotype A2 (15.3%) were also found. Genotype G sequence analysis suggests distinct introductions of this genotype in the country. Furthermore, we estimated the time of the most recent common ancestor (TMRCA) for each HBV/F subgenotype and also for Colombian F3 sequences using two different datasets: (i) 77 sequences comprising 1306 bp of S/POL region and (ii) 283 sequences comprising 681 bp of S/POL region. We also used two other previously estimated evolutionary rates: (i) 2.60 × 10(-4)s/s/y and (ii) 1.5 × 10(-5)s/s/y. Here we report the HBV genotypes circulating in Colombia and estimated the TMRCA for the four different subgenotypes of genotype F.

  11. HBV genotypic variability in Cuba.

    Science.gov (United States)

    Loureiro, Carmen L; Aguilar, Julio C; Aguiar, Jorge; Muzio, Verena; Pentón, Eduardo; Garcia, Daymir; Guillen, Gerardo; Pujol, Flor H

    2015-01-01

    The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%), mainly A2 (149, 60%) but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%), with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7). Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions.

  12. HBV Genotypic Variability in Cuba

    Science.gov (United States)

    Loureiro, Carmen L.; Aguilar, Julio C.; Aguiar, Jorge; Muzio, Verena; Pentón, Eduardo; Garcia, Daymir; Guillen, Gerardo; Pujol, Flor H.

    2015-01-01

    The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed. The most frequent genotype was A (167/250, 67%), mainly A2 (149, 60%) but also A1 and one A4. A total of 77 isolates were classified as genotype D (31%), with co-circulation of several subgenotypes (56 D4, 2 D1, 5 D2, 7 D3/6 and 7 D7). Three isolates belonged to genotype E, two to H and one to B3. Complete genome sequence analysis of selected isolates confirmed the phylogenetic analysis performed with the S region. Mutations or polymorphisms in precore region were more common among genotype D compared to genotype A isolates. The HBV genotypic distribution in this Caribbean island correlates with the Y lineage genetic background of the population, where a European and African origin prevails. HBV genotypes E, B3 and H isolates might represent more recent introductions. PMID:25742179

  13. Effects of a novel encapsulating technique on the temperature tolerance and anti-colitis activity of the probiotic bacterium Lactobacillus kefiranofaciens M1.

    Science.gov (United States)

    Wang, Sheng-Yao; Ho, Yi-Fang; Chen, Yen-Po; Chen, Ming-Ju

    2015-04-01

    Lactobacillus kefiranofaciens M1 (M1) has been shown to possess many different beneficial health effects including anti-colitis activity. The purpose of this study was to develop a novel and easily scaled-up encapsulating technique that would improve the temperature tolerance of the bacterium and reduce the sensitivity of the organism to gastrointestinal fluid. A mixture of sodium alginate, gellan gum and skim milk powder was used as a coating material to entrap M1. The M1 gel was then directly freeze dried in order to dehydrate the covering and form microcapsules. The viable cell numbers of M1 present only dropped ten folds after the freeze-drying encapsulation process. The viable cell counts remained constant at 5 × 10(7) CFU/g after heating from 25 °C to 75 °C and holding at 75 °C for 1 min. The viable cell counts were reduced to 10(6) CFU/g and 10(5) CFU/g after 8-week storage at 4 °C and subsequent heat treatment with simulated gastrointestinal fluid test (SGFT) and bile salts, respectively. The effect of encapsulated M1 on the organism's anti-colitis activity was evaluated using the dextran sodium sulfate (DSS) induced colitis mouse model. An in vivo study indicated that administration of heat treated encapsulated M1 was able to ameliorate DSS-induced colitis producing a significant reduction in the bleeding score and an attenuation of inflammatory score. These findings clearly demonstrate that encapsulation of M1 using this novel technique is able to provide good protection from temperature changes and SGFT treatment and also does not affect the organism's anti-colitis activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway.

    Science.gov (United States)

    Park, Y-H; Kim, S-U; Kwon, T-H; Kim, J-M; Song, I-S; Shin, H-J; Lee, B-K; Bang, D-H; Lee, S-J; Lee, D-S; Chang, K-T; Kim, B-Y; Yu, D-Y

    2016-07-07

    The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.

  15. Phenotypic and genotypic characterisation of Burkholderia cenocepacia J2315 mutants affected in homoserine lactone and diffusible signal factor-based quorum sensing systems suggests interplay between both types of systems.

    Directory of Open Access Journals (Sweden)

    Claudia Udine

    Full Text Available Many putative virulence factors of Burkholderia cenocepacia are controlled by various quorum sensing (QS circuits. These QS systems either use N-acyl homoserine lactones (AHL or cis-2-dodecenoic acid ("Burkholderia diffusible signal factor", BDSF as signalling molecules. Previous work suggested that there is little cross-talk between both types of systems. We constructed mutants in B. cenocepacia strain J2315, in which genes encoding CepI (BCAM1870, CciI (BCAM0239a and the BDSF synthase (BCAM0581 were inactivated, and also constructed double (ΔcepIΔBCAM0581, ΔcciIΔBCAM0581 and ΔcepIΔcciI mutants and a triple (ΔcepIΔcciIΔBCAM0581 mutant. Subsequently we investigated phenotypic properties (antibiotic susceptibility, biofilm formation, production of AHL and BDSF, protease activity and virulence in Caenorhabditis elegans and measured gene expression in these mutants, and this in the presence and absence of added BDSF, AHL or both. The triple mutant was significantly more affected in biofilm formation, antimicrobial susceptibility, virulence in C. elegans, and protease production than either the single or double mutants. The ΔBCAM0581 mutant and the ΔcepIΔBCAM0581 and ΔcciIΔBCAM0581 double mutants produced significantly less AHL compared to the WT strain and the ΔcepI and ΔcciI single mutant, respectively. The expression of cepI and cciI in ΔBCAM0581, was approximately 3-fold and 7-fold (p<0.05 lower than in the WT, respectively. The observed differences in AHL production, expression of cepI and cciI and QS-controlled phenotypes in the ΔBCAM0581 mutant could (at least partially be restored by addition of BDSF. Our data suggest that, in B. cenocepacia J2315, AHL and BDSF-based QS systems co-regulate the same set of genes, regulate different sets of genes that are involved in the same phenotypes and/or that the BDSF system controls the AHL-based QS system. As the expression of the gene encoding the C6-HSL synthase CciI (and to a

  16. Dynamic Changes of Microglia/Macrophage M1 and M2 Polarization in Theiler's Murine Encephalomyelitis.

    Science.gov (United States)

    Herder, Vanessa; Iskandar, Cut Dahlia; Kegler, Kristel; Hansmann, Florian; Elmarabet, Suliman Ahmed; Khan, Muhammad Akram; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner; Beineke, Andreas

    2015-11-01

    Microglia and macrophages play a central role for demyelination in Theiler's murine encephalomyelitis (TME) virus infection, a commonly used infectious model for chronic-progressive multiple sclerosis. In order to determine the dynamic changes of microglia/macrophage polarization in TME, the spinal cord of Swiss Jim Lambert (SJL) mice was investigated by gene expression profiling and immunofluorescence. Virus persistence and demyelinating leukomyelitis were confirmed by immunohistochemistry and histology. Electron microscopy revealed continuous myelin loss together with abortive myelin repair during the late chronic infection phase indicative of incomplete remyelination. A total of 59 genes out of 151 M1- and M2-related genes were differentially expressed in TME virus-infected mice over the study period. The onset of virus-induced demyelination was associated with a dominating M1 polarization, while mounting M2 polarization of macrophages/microglia together with sustained prominent M1-related gene expression was present during the chronic-progressive phase. Molecular results were confirmed by immunofluorescence, showing an increased spinal cord accumulation of CD16/32(+) M1-, arginase-1(+) M2- and Ym1(+) M2-type cells associated with progressive demyelination. The present study provides a comprehensive database of M1-/M2-related gene expression involved in the initiation and progression of demyelination supporting the hypothesis that perpetuating interaction between virus and macrophages/microglia induces a vicious circle with persistent inflammation and impaired myelin repair in TME.

  17. Reverse phase liquid chromatographic determination and confirmation of aflatoxin M1 in cheese.

    Science.gov (United States)

    Hisada, K; Terada, H; Yamamoto, K; Tsubouchi, H; Sakabe, Y

    1984-01-01

    A systematic method is proposed for determination and confirmation of aflatoxin M1 in cheese by liquid chromatography (LC). A sample of cheese is extracted with chloroform, cleaned up on 2 silica gel columns followed by a Sep-Pak C18 cartridge, and chromatographed on a 5 microns octadecyl silica column with fluorometric detection. The sample extract or standard is treated with n-hexane-trifluoroacetic acid (TFA) (4 + 1) for 30 min at 40 degrees C. Analysis by LC with TFA-treatment of the extract provides quantitative data. Multiple assays of 5 samples of Gouda cheese spiked with aflatoxin M1 at levels of 0.5, 0.1, and 0.05 ng/g showed average recoveries of 93.2, 91.6, and 92.4%, with coefficients of variation of 2.63, 3.97, and 4.52%, respectively. Assay of 5 naturally contaminated cheeses resulted in 0.051-0.448 ng/g of aflatoxin M1. Limit of quantitation is about 0.01 ng/g. The identity of aflatoxin M1 is confirmed by treating aflatoxin M1 or the M2a derivative with TFA-methanol (or ethanol) (3 + 1). The TFA-methanol reaction products of M2a could be detected quantitatively.

  18. Evolutionary Trajectories of Beta-Lactamase CTX-M-1 Cluster Enzymes: Predicting Antibiotic Resistance

    Science.gov (United States)

    Novais, Ângela; Comas, Iñaki; Baquero, Fernando; Cantón, Rafael; Coque, Teresa M.; Moya, Andrés; González-Candelas, Fernando; Galán, Juan-Carlos

    2010-01-01

    Extended-spectrum beta-lactamases (ESBL) constitute a key antibiotic-resistance mechanism affecting Gram-negative bacteria, and also an excellent model for studying evolution in real time. A shift in the epidemiology of ESBLs is being observed, which is characterized by the explosive diversification and increase in frequency of the CTX-M-type β-lactamases in different settings. This provides a unique opportunity for studying a protein evolutionary radiation by the sequential acquisition of specific mutations enhancing protein efficiency and fitness concomitantly. The existence of driver antibiotic molecules favoring protein divergence has been investigated by combining evolutionary analyses and experimental site-specific mutagenesis. Phylogenetic reconstruction with all the CTX-M variants described so far provided a hypothetical evolutionary scenario showing at least three diversification events. CTX-M-3 was likely the enzyme at the origin of the diversification in the CTX-M-1 cluster, which was coincident with positive selection acting on several amino acid positions. Sixty-three CTX-M-3 derivatives containing all combinations of mutations under positively selected positions were constructed, and their phenotypic efficiency was evaluated. The CTX-M-3 diversification process can only be explained in a complex selective landscape with at least two antibiotics (cefotaxime and ceftazidime), indicating the need to invoke mixtures of selective drivers in order to understand the final evolutionary outcome. Under this hypothesis, we found congruent results between the in silico and in vitro analyses of evolutionary trajectories. Three pathways driving the diversification of CTX-M-3 towards the most complex and efficient variants were identified. Whereas the P167S pathway has limited possibilities of further diversification, the D240G route shows a robust diversification network. In the third route, drift may have played a role in the early stages of CTX-M-3 evolution

  19. N-Acetyltransferase 2 and glutathione s-transferase M1 in colon and rectal cancer cases from an industrialized area.

    Science.gov (United States)

    Golka, Klaus; Roemer, Hermann C; Weistenhöfer, Wobbeke; Blaszkewicz, Meinolf; Hammad, Seddik; Reckwitz, Thomas; Loehlein, Dietrich; Hartel, Mark; Hengstler, Jan G; Geller, Frank

    2012-01-01

    Apart from genetics, nutrition, and environment, occupational factors also play an important role in colon and rectal cancer development. The aim of this study was to examine these cancer types in an area of former coal, iron, and steel industries, which was found to display an increased incidence of colon cancer mortality. N-Acetyltransferase 2 (NAT2) and glutathione S-transferase M1 (GSTM1) genotypes were investigated in 108 colon cancer cases, 80 rectum cancer cases, and 188 controls (suffering from nonmalignant diseases). Further, in a pilot study, 28 colorectal cancer patients were NAT2 phenotyped by the caffeine test. Possible occupational and nonoccupational risk factors were investigated by a personal interview. The frequency of rapid NAT2 genotype was 35% in colon cancer cases, 47% in rectal cancer cases, and 42% in controls (GSTM1 0/0 genotype: 53, 46, and 47%, respectively). In the 29 patients with cancer in the ascending colon, 10% were of the rapid NAT2 genotype. In the pilot study the frequency of the rapid NAT2 phenotype was 49%. The only major professional group with an elevated risk was painters (colon cancer OR 2.48, 95% CI 0.4-15.23; rectal cancer OR 5.65, 95% CI 1.06-30.21). In contrast to early studies, in the present study the slow NAT2 status is overrepresented. As colorectal cancer is associated with nutrition and physical activity, present findings may be due to excessive physical heavy work and the resulting nutrition in this area.

  20. E1, M1, E2 transition energies and probabilities of W$^{54+}$ ions

    CERN Document Server

    Ding, Xiao-bin; Liu, Jia-xin; Koike, Fumihiro; Murakami, Izumi; Kato, Daiji; Sakaue, Hiroyuki A; Nakamura, Nobuyuki; Dong, Chen-zhong

    2016-01-01

    A comprehensive theoretical study of the E1, M1, E2 transitions of Ca-like tungsten ions is presented. Using multi-configuration Dirac-Fock (MCDF) method with a restricted active space treatment, the wavelengths and probabilities of the M1 and E2 transitions between the multiplets of the ground state configuration ([Ne]3s$^{2}$3p$^{6}$3d$^{2}$) and of the E1 transitions between [Ne]3s$^{2}$3p$^{5}$3d$^{3}$ and [Ne]3s$^{2}$3p$^{6}$3d$^{2}$ have been calculated. The results are in reasonable agreement with available experimental data. The present E1 and M1 calculations are compared with previous theoretical values. For E2 transitions, the importance of electron correlation from 3s and 3p orbitals is pointed out. Several strong E1 transitions are predicted, which have potential advantage for plasma diagnostics.

  1. Attenuation of cocaine's reinforcing and discriminative stimulus effects via muscarinic M1 acetylcholine receptor stimulation

    DEFF Research Database (Denmark)

    Thomsen, Morgane; Conn, P Jeffrey; Lindsley, Craig

    2010-01-01

    Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and extend in the mouse species findings that nonselective muscarinic receptor antagonists can enhance cocaine's discriminative stimulus....... More importantly, we tested the hypothesis that muscarinic receptor agonists with varied receptor subtype selectivity can blunt cocaine's discriminative stimulus and reinforcing effects; we hypothesized a critical role for the M(1) and/or M(4) receptor subtypes in this modulation. Mice were trained...... to discriminate cocaine from saline, or to self-administer intravenous cocaine chronically. The nonselective muscarinic antagonists scopolamine and methylscopolamine, the nonselective muscarinic agonists oxotremorine and pilocarpine, the M(1)/M(4)-preferring agonist xanomeline, the putative M(1)-selective agonist...

  2. Nonlinear {omega}*-stabilization of the m = 1 mode in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, B. [Univ. of Maryland, College Park, MD (United States). Inst. for Plasma Research; Zakharov, L. [Princeton Univ., NJ (United States). Plasma Physics Lab.

    1995-08-01

    Earlier studies of sawtooth oscillations in Tokamak Fusion Test Reactor supershots (Levinton et al, Phys. Rev. Lett. 72, 2895 (1994); Zakharov, et al, Plasma Phys. and Contr. Nucl. Fus. Res., Proc. 15th Int. Conf., Seville 1994, Vienna) have found an apparent contradiction between conventional linear theory and experiment: even in sawtooth-free discharges, the theory typically predicts instability due to a nearly ideal m = 1 mode. Here, the nonlinear evolution of such mode is analyzed using numerical simulations of a two-fluid magnetohydrodynamic (MHD) model. We find the mode saturates nonlinearly at a small amplitude provided the ion and electron drift-frequencies {omega}*{sub i,e} are somewhat above the linear stability threshold of the collisionless m = 1 reconnecting mode. The comparison of the simulation results to m = 1 mode activity in TFTR suggests additional, stabilizing effects outside the present model are also important.

  3. (Phaseolus vulgaris L) Genotypes

    African Journals Online (AJOL)

    Drought stress did not affect the concentration of sucrose in ... photosynthetic rate thereby disrupting carbohydrate metabolism in leaves (Kim et al. 2000). .... quantified by this method was multiplied by an approximate factor of 6.25 to estimate.

  4. M1 AFLATOXIN, TOTAL BACTERIAL COUNT AND SOMATIC CELL COUNT IN ORGANIC AND CONVENTIONAL MILK

    Directory of Open Access Journals (Sweden)

    M. Trevisani

    2009-09-01

    Full Text Available Comparative quality evaluation of organic and conventional milk produced in similar environmental condition was performed. Bulk-tank milk was sampled once a week during 30 weeks from 10 organic and 10 conventional dairy farms where aflatoxin M1 level was previous tested during 11 months on bulk-tank milk from tanker at the processing plant. Somatic Cells and Total Microbial Counts did not show differences that can be related to the organic production system, suggesting an effect induced by farm size and technical factors. Higher level of Aflatoxin M1 was found in organic than conventional milk.

  5. Imputation of missing genotypes: an empirical evaluation of IMPUTE

    Directory of Open Access Journals (Sweden)

    Steinberg Martin H

    2008-12-01

    Full Text Available Abstract Background Imputation of missing genotypes is becoming a very popular solution for synchronizing genotype data collected with different microarray platforms but the effect of ethnic background, subject ascertainment, and amount of missing data on the accuracy of imputation are not well understood. Results We evaluated the accuracy of the program IMPUTE to generate the genotype data of partially or fully untyped single nucleotide polymorphisms (SNPs. The program uses a model-based approach to imputation that reconstructs the genotype distribution given a set of referent haplotypes and the observed data, and uses this distribution to compute the marginal probability of each missing genotype for each individual subject that is used to impute the missing data. We assembled genome-wide data from five different studies and three different ethnic groups comprising Caucasians, African Americans and Asians. We randomly removed genotype data and then compared the observed genotypes with those generated by IMPUTE. Our analysis shows 97% median accuracy in Caucasian subjects when less than 10% of the SNPs are untyped and missing genotypes are accepted regardless of their posterior probability. The median accuracy increases to 99% when we require 0.95 minimum posterior probability for an imputed genotype to be acceptable. The accuracy decreases to 86% or 94% when subjects are African Americans or Asians. We propose a strategy to improve the accuracy by leveraging the level of admixture in African Americans. Conclusion Our analysis suggests that IMPUTE is very accurate in samples of Caucasians origin, it is slightly less accurate in samples of Asians background, but substantially less accurate in samples of admixed background such as African Americans. Sample size and ascertainment do not seem to affect the accuracy of imputation.

  6. Genotype transposer: automated genotype manipulation for linkage disequilibrium analysis.

    Science.gov (United States)

    Cox, D G; Canzian, F

    2001-08-01

    The purpose of this work is to provide the modern molecular geneticist with tools to perform more efficient and more accurate analysis of the genotype data they produce. By using Microsoft Excel macros written in Visual Basic, we can translate genotype data into a form readable by the versatile software 'Arlequin', read the Arlequin output, calculate statistics of linkage disequilibrium, and put the results in a format for viewing with the software 'GOLD'. The software is available by FTP at: ftp://xcsg.iarc.fr/cox/Genotype_Transposer/. Detailed instruction and examples are available at: ftp://xcsg.iarc.fr/cox/Genotype&_Transposer/. Arlequin is available at: http://lgb.unige.ch/arlequin/. GOLD is available at: http://www.well.ox.ac.uk/asthma/GOLD/.

  7. Expression and functional activity of bitter taste receptors in primary renal tubular epithelial cells and M-1 cells.

    Science.gov (United States)

    Liang, Jie; Chen, Fuxue; Gu, Fu; Liu, Xin; Li, Feng; Du, Dongshu

    2017-04-01

    The kidney is essential in the maintenance of in vivo homeostasis by body fluid and electrolyte conservation and metabolic waste removal. Previously, we reported the expression of a novel G protein family (Tas2rs), which includes bitter taste receptors, in the kidney tubule system, including the nephrons and the collecting duct system. Bitter taste receptors could affect kidney function via Ca(2+) intake. Alkaloids such as phenylthiocarbamide stimulate these receptors and cause an increase in Ca(2+) intake. In this study, we determined the expression of bitter taste receptors in the immature kidney and small intestine and in primary renal epithelial cells and M-1 (collecting tubule cell line) cells, by using QPCR and immunostaining. We found no expression of bitter taste receptors in the immature kidney and small intestine several days after birth; the relative abundance of Tas2rs transcripts varied depending on the developmental stage. Tas2rs were expressed in primary renal epithelial cells and M-1 cells. The traditional Chinese medicinal plant extracts phellodendrine and coptisine caused a rapid rise in intracellular Ca(2+) concentration, which was inhibited by the phospholipase C (PLC) inhibitor U-73122. Thus, phellodendrine and coptisine could change the physiological status of renal cells in vitro by mediation of bitter taste receptors in a PLC-dependent manner. Our results provide new insights on the expression and role of bitter taste receptors in renal development and function.

  8. Recent Development of QCD Factorization for B-> M1 M2

    CERN Document Server

    Yang, Deshan

    2010-01-01

    After briefly introducing the framework of QCD factorization for B-> M1 M2 in the language of the Soft-Collinear Effective Theory, we firstly address the recent efforts on higher-order radiative corrections in QCD factorization. Then we discuss some phenomenologies in B-> V V within the framework of QCD factorization.

  9. 26 CFR 31.3306(m)-1 - American vessel and aircraft.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false American vessel and aircraft. 31.3306(m)-1... vessel and aircraft. (a) The term “American vessel” means any vessel which is documented (that is....) (b) The term “American aircraft” means any aircraft registered under the laws of the United States...

  10. M1 corticospinal mirror neurons and their role in movement suppression during action observation.

    Science.gov (United States)

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N; Kraskov, Alexander

    2013-02-04

    Evidence is accumulating that neurons in primary motor cortex (M1) respond during action observation, a property first shown for mirror neurons in monkey premotor cortex. We now show for the first time that the discharge of a major class of M1 output neuron, the pyramidal tract neuron (PTN), is modulated during observation of precision grip by a human experimenter. We recorded 132 PTNs in the hand area of two adult macaques, of which 65 (49%) showed mirror-like activity. Many (38 of 65) increased their discharge during observation (facilitation-type mirror neuron), but a substantial number (27 of 65) exhibited reduced discharge or stopped firing (suppression-type). Simultaneous recordings from arm, hand, and digit muscles confirmed the complete absence of detectable muscle activity during observation. We compared the discharge of the same population of neurons during active grasp by the monkeys. We found that facilitation neurons were only half as active for action observation as for action execution, and that suppression neurons reversed their activity pattern and were actually facilitated during execution. Thus, although many M1 output neurons are active during action observation, M1 direct input to spinal circuitry is either reduced or abolished and may not be sufficient to produce overt muscle activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. A fluorescence anisotropy assay for the muscarinic M1 G-protein-coupled receptor.

    Science.gov (United States)

    Huwiler, Kristin G; De Rosier, Therese; Hanson, Bonnie; Vogel, Kurt W

    2010-06-01

    In the search for new chemical entities that interact with G-proteincoupled receptors (GPCRs), assays that quantify efficacy and affinity are employed. Traditional methods for measuring affinity involve radiolabeled ligands. To address the need for homogeneous biochemical fluorescent assays to characterize orthosteric ligand affinity and dissociation rates, we have developed a fluorescence anisotropy (FA) assay for the muscarinic M1 receptor that can be conducted in a 384-well plate. We used membranes from a muscarinic M1 cell line optimized for high-throughput functional assays and the previously characterized fluorescent antagonist BODIPY FL pirenzepine. The affinities of reference compounds were determined in the competitive FA assay and compared with those obtained with a competitive filter-based radioligand-binding assay using [(3)H] N-methylscopolamine. The IC(50) values produced from the FA assay were well-correlated with the radioligand-binding K(i) values (R(2) = 0.98). The dissociation of the BODIPY FL pirenzepine was readily monitored in real time using the FA assay and was sensitive to the presence of the allosteric modulator gallamine. This M1 FA assay offers advantages over traditional radioligandbinding assays as it eliminates radioactivity while allowing investigation of orthosteric or allosteric muscarinic M1 ligands in a homogeneous format.

  12. Stereospecific reduction of virginiamycin M1 as the virginiamycin resistance pathway in Streptomyces virginiae.

    Science.gov (United States)

    Lee, C K; Minami, M; Sakuda, S; Nihira, T; Yamada, Y

    1996-03-01

    In a cell extract of Streptomyces virginiae, virginiamycin M1 was inactivated in the presence of NADPH, while virginiamycin S remained intact. The inactivated product of virginiamycin M1 was isolated, and structure analysis revealed that the inactivation involves reduction of a C-16 carbonyl group leading to the formation of 16-dihydrovirginiamycin M1. Acetonide and benzylidene acetal derivatives were synthesized from the two hydroxyl groups on C-14 and C-16, and the C-16 stereochemistry was determined by 13C nuclear magnetic resonance spectroscopy. Two methyl groups of the acetonide derivative gave 13C signals of 20.1 and 30.1 ppm, indicating that the relative stereochemistry of the C-14 and C-16 hydroxy groups is syn. Furthermore, irradiation of the benzylidene methine proton gave clear nuclear Overhauser effect enhancement of the C-14 or C-16 methine protons, indicating that H-14 and H-16 were in an axial configuration. From the (14S) absolute configuration of natural virginiamycin M1 and the syn relative configuration for the C-14 and C-16 hydroxyl groups of the inactivated product, the C-16 absolute configuration of the inactivated product was thus identified as R.

  13. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  14. Molecular mechanisms that regulate the macrophage M1/M2 polarization balance

    Directory of Open Access Journals (Sweden)

    Nan eWang

    2014-11-01

    Full Text Available As an essential component of innate immunity, macrophages have multiple functions in both inhibiting or promoting cell proliferation and tissue repair. Diversity and plasticity are hallmarks of macrophages. Classical M1 and alternative M2 activation of macrophages, mirroring the Th1–Th2 polarization of T cells, represent two extremes of a dynamic changing state of macrophage activation. M1-type macrophages release cytokines that inhibit the proliferation of surrounding cells and damage contiguous tissue, and M2-type macrophages release cytokines that promote the proliferation of contiguous cells and tissue repair. M1-M2 polarization of macrophage is a tightly controlled process entailing a set of signaling pathways, transcriptional and posttranscriptional regulatory networks. An imbalance of macrophage M1-M2 polarization is often associated with various diseases or inflammatory conditions. Therefore identification of the molecules associated with the dynamic changes of macrophage polarization and understanding their interactions is crucial for elucidating the molecular basis of disease progression and designing novel macrophage-mediated therapeutic strategies.

  15. A Busy period analysis for the state dependent M/M/1/K queue

    NARCIS (Netherlands)

    Al Hanbali, Ahmad; Boxma, Onno

    2010-01-01

    In this paper, we study the transient behavior of a state dependent M/M/1/K queue during the busy period. We derive in closed-form the joint transform of the length of the busy period, the number of customers served during the busy period, and the number of losses during the busy period. For two

  16. Aflatoxin M1 in raw milk and binding of aflatoxin by lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Aflatoxin M1 in raw milk and binding of aflatoxin by lactic acid bacteria

    2010-12-01

    Full Text Available Aflatoxin M1 (AFM1 is potential human carcinogen. Its presence in milk and dairy products represents risk for human health. Therefore, this study was carried out in order to determine thedegree of microbiological contamination by mold, and the potential presence of aflatoxin M1 in 60 raw milk samples, randomly taken from individual producers from different regions of the continental Croatia. The most common genera isolated fungi were Geotrichum (78.3 %, Aspergillus (32.4 % and Penicillium (27.0 %. From total of 60 studied milk samples, 86.66 % were positive for the presence of aflatoxin M1, and 6.66 % of samples were above the prescribed limits. Lactic acid bacteria used in fermented dairy products as a starter culture may play a role in reduction of aflatoxin in foods and nutrients. In this paper the ability of lactic acid bacteria: Lactobacillus rhamnosus GG (ATCC 53103, Lactobacillus delbrueckii S1 and Lactobacillus plantarum A1 to bind aflatoxin M1 was investigated. Standard strain L. rhamnosus GG (ATCC 53103 and L. delbrueckii S1 can significantly (P50 % compared to L. plantarum A1, which binds AFM1 between 18.7 to 28.7 %.

  17. Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype

    Science.gov (United States)

    Xue, Nina; Zhou, Qin; Ji, Ming; Jin, Jing; Lai, Fangfang; Chen, Ju; Zhang, Mengtian; Jia, Jing; Yang, Huarong; Zhang, Jie; Li, Wenbin; Jiang, Jiandong; Chen, Xiaoguang

    2017-01-01

    Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2-polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeutic approach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage. PMID:28045028

  18. Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.

    Science.gov (United States)

    Jiang, Xingwei; Yu, Jiahui; Shi, Qingzhu; Xiao, Yan; Wang, Wei; Chen, Guojiang; Zhao, Zhi; Wang, Renxi; Xiao, He; Hou, Chunmei; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Wang, Lili; Li, Yan; Han, Gencheng

    2015-10-01

    Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy.

  19. Experimental Conditions: SE18_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available liver and brain by Orbitrap MS and automated search engine Lipid Search SE18_S1 Mouse liver SE18_S1_M1 34.1...phy. SE18_MS1 Preparation of lipid extract and ESI negative detection by LC-MS analysis SE18_DS1 Identification of phospholipids with Lipid Search default ...

  20. Experimental Conditions: SE18_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available liver and brain by Orbitrap MS and automated search engine Lipid Search SE18_S2 Mouse brain SE18_S2_M1 10.8...phy. SE18_MS1 Preparation of lipid extract and ESI negative detection by LC-MS analysis SE18_DS1 Identification of phospholipids with Lipid Search default ...

  1. Design of an E-ELT M1 segment measurement machine with nanometer accuracy

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.; Voert, M.J.A. te

    2014-01-01

    The baseline design of the European Extremely Large Telescope features a telescope with a 39-meter-class primary mirror (M1), consisting of 798 hexagonal segments. A measurement machine design is presented based on a non-contact single-point scanning technique, capable of measuring the form error of

  2. Experimental Conditions: SE37_S16_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S16 Blank (80% methanol) SE37_S16_M1 0mg [MassBase ID] MDLC1_43484 SE37_MS1 Metabolites extraction... with 80% methanol and analysis by LC-Orbitrap-MS SE37_DS1 Peak extraction for unlabeled data 6|ITMS 2 ...

  3. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  4. Aflatoxin M1 in white cheese and butter consumed in Istanbul, Turkey.

    Science.gov (United States)

    Aycicek, Hasan; Yarsan, Ender; Sarimehmetoglu, Belgin; Cakmak, Omer

    2002-10-01

    We studied the occurrence of Aflatoxin M1 (AFM1) in 183 sample of white cheese and butter in Istanbul, Turkey in 2001. The incidence of AFM1 in white cheese and butter samples was as high as 65 and 81, respectively. The particularly high AFM,concentrations imply that more importance should be given to routine analysis of these dairy products.

  5. Proteome Differences between Hepatitis B Virus Genotype-B- and Genotype-C-Induced Hepatocellular Carcinoma Revealed by iTRAQ-Based Quantitative Proteomics.

    Science.gov (United States)

    Wei, Dahai; Zeng, Yongyi; Xing, Xiaohua; Liu, Hongzhi; Lin, Minjie; Han, Xiao; Liu, Xiaolong; Liu, Jingfeng

    2016-02-05

    Hepatitis B virus (HBV) is the main cause of hepatocellular carcinoma (HCC) in southeast Asia where HBV genotype B and genotype C are the most prevalent. Viral genotypes have been reported to significantly affect the clinical outcomes of HCC. However, the underlying molecular differences among different genotypes of HBV virus infected HCC have not been revealed. Here, we applied isobaric tags for relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify the proteome differences between the HBV genotypes B- and C-induced HCC. In brief, a total of 83 proteins in the surrounding noncancerous tissues and 136 proteins in the cancerous tissues between HBV genotype-B- and genotype-C-induced HCC were identified, respectively. This information revealed that there might be different molecular mechanisms of the tumorigenesis and development of HBV genotypes B- and C-induced HCC. Furthermore, our results indicate that the two proteins ARFIP2 and ANXA1 might be potential biomarkers for distinguishing the HBV genotypes B- and C-induced HCC. Thus, the quantitative proteomic analysis revealed molecular differences between the HBV genotypes B- and C-induced HCC, and might provide fundamental information for further deep study.

  6. Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China

    Directory of Open Access Journals (Sweden)

    Ines Pinto-Ribeiro

    2016-05-01

    Full Text Available Helicobacter pylori is the major triggering factor for gastric carcinoma, but only a small proportion of infected patients develop this disease. Differences in virulence observed among H. pylori strains, namely in the vacuolating cytotoxin vacA gene, may contribute to this discrepancy. Infection with vacA s1, i1 and m1 strains increases the risk for progression of gastric premalignant lesions and for gastric carcinoma. However, in East Asian countries most of the H. pylori strains are vacA s1, regardless of the patients’ clinical status, and the significance of the vacA i1 and m1 genotypes for gastric carcinoma in this geographic area remains to be fully elucidated. The aim of the present study was to investigate this relationship in 290 patients from Macau, China. Using very sensitive and accurate genotyping methods, we detected infection with vacA i1 and with vacA m1 strains in, respectively, 85.2% and 52.6% of the patients that were infected with single genotypes. The prevalence of cagA-positive strains was 87.5%. No significant associations were observed between vacA genotypes or cagA and gastric carcinoma. It is worth noting that 37.5% of the infected patients had coexistence of H. pylori strains with different vacA genotypes. Additional studies directed to other H. pylori virulence factors should be performed to identify high risk patients in East Asia.

  7. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity.

    Science.gov (United States)

    Zhirnov, O P; Manykin, A A; Rossman, J S; Klenk, H D

    2016-05-01

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~ 25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Increased SMA-M1 coherence in Parkinson's disease - Pathophysiology or compensation?

    Science.gov (United States)

    Pollok, Bettina; Kamp, Daniel; Butz, Markus; Wojtecki, Lars; Timmermann, Lars; Südmeyer, Martin; Krause, Vanessa; Schnitzler, Alfons

    2013-09-01

    Parkinson's disease (PD) is a common neurodegenerative disorder owing to loss of dopaminergic cells. Akinesia - one of the core symptoms of PD - is associated with exaggerated oscillations at beta frequency (13-30 Hz) within the subthalamic nucleus (STN). Thus, enhanced oscillations below 30 Hz are assumed to represent a pathophysiological marker of PD. However, recent data suggest that OFF medication exaggerated beta oscillations within basal ganglia (BG) cortical networks may serve for the compensation of BG dysfunctions. The STN is functionally connected to mesial prefrontal areas like the supplementary motor area (SMA). But, it is still not fully understood how enhanced beta oscillations within the BG exert dominance over the primary motor cortex (M1) thereby yielding motor impairment. The present study, therefore, investigates the effect of dopaminergic state on SMA-M1 functional connectivity using Magnetoencephalography (MEG). MEG data were recorded in 7 patients suffering from PD with preponderance of akinesia during isometric contraction of the right forearm and during rest. Coherence as a measure of functional connectivity between M1 and SMA was calculated OFF and ON medication and correlated with the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) and with disease duration. During rest a significant positive correlation between disease duration and SMA-M1 coherence was found ON but not OFF medication. Conversely, during isometric contraction SMA-M1 coherence and UPDRS III were inversely correlated OFF but not ON medication explaining more than 80% of variance. The results favor the hypothesis that OFF medication exaggerated cortical coherence at beta frequency represents a compensatory mechanism rather than a pathophysiological marker per se. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Balancing the excitability of M1 circuitry during movement observation without overt replication

    Directory of Open Access Journals (Sweden)

    Pablo eArias

    2014-09-01

    Full Text Available Although observation of a movement increases the excitability of the motor system of the observer, it does not induce a motor replica. What is the mechanism for replica suppression? We performed a series of experiments, involving a total of 66 healthy humans, to explore the excitability of different M1 circuits and the spinal cord during observation of simple movements. Several strategies were used. In the first and second experimental blocks, we used several delay times from movement onset to evaluate the time-course modulation of the cortico-spinal excitability (CSE, and its potential dependency on the duration of the movement observed; in order to do this single pulse transcranial magnetic stimulation (TMS over M1 was used. In subsequent experiments, at selected delay times from movement-onset, we probed the excitability of the cortico-spinal circuits using three different approaches: i electric cervicomedullary stimulation, to test spinal excitability, ii paired-pulse TMS over M1, to evaluate the cortical inhibitory-excitatory balance (short intracortical inhibition SICI and intracortical facilitation ICF and iii continuous theta-burst stimulation (cTBS, to modulate the excitability of M1cortical circuits. We observed a stereotyped response in the modulation of CSE. At 500ms after movement-onset the ICF was increased; although the most clear-cut effect was a decrease of CSE. The compensatory mechanism was not explained by changes in SICI, but by M1-intracortical circuits targeted by cTBS. Meanwhile, the spinal cord maintained the elevated level of excitability induced when expecting to observe movements, potentially useful to facilitate any required response to the movement observed.

  10. growth and yield parameters of sorghum genotypes as affected by ...

    African Journals Online (AJOL)

    DR. AMINU

    showing symptoms usually matured earlier and produced less grain yield. Keywords ... cassava, citrus, coconut, corn (maize), oats, peanut, ...... America to long smut. (SoroposporiumehrenberghiiVanky). Crop. Protection 26: 1771–. 1776.

  11. VO2 max is associated with ACE genotype in postmenopausal women.

    Science.gov (United States)

    Hagberg, J M; Ferrell, R E; McCole, S D; Wilund, K R; Moore, G E

    1998-11-01

    Relationships have frequently been found between angiotensin-converting enzyme (ACE) genotype and various pathological and physiological cardiovascular outcomes and functions. Thus we sought to determine whether ACE genotype affected maximal O2 consumption (VO2 max) and maximal exercise hemodynamics in postmenopausal women with different habitual physical activity levels. Age, body composition, and habitual physical activity levels did not differ among ACE genotype groups. However, ACE insertion/insertion (II) genotype carriers had a 6.3 ml . kg-1 . min-1 higher VO2 max (P VO2 max (P VO2 max than the DD genotype group, but the difference was not significant. ACE genotype accounted for 12% of the variation in VO2 max among women after accounting for the effect of habitual physical activity levels. The entire difference in VO2 max among ACE genotype groups was the result of differences in maximal arteriovenous O2 difference (a-vDO2). ACE genotype accounted for 17% of the variation in maximal a-vDO2 in these women. Maximal cardiac output index did not differ whatsoever among ACE genotype groups. Thus it appears that ACE genotype accounts for a significant portion of the interindividual differences in VO2 max among these women. However, this difference is the result of genotype-dependent differences in maximal a-vDO2 and not of maximal stroke volume and maximal cardiac output.

  12. Immunohistochemical localisation of cholinergic muscarinic receptor subtype 1 (M1r) in the guinea pig and human enteric nervous system.

    Science.gov (United States)

    Harrington, A M; Hutson, J M; Southwell, B R

    2007-07-01

    Little is known regarding the location of cholinergic muscarinic receptor 1 (M1r) in the ENS, even though physiological data suggest that M1rs are central to cholinergic neurotransmission. This study localised M1rs in the ENS of the guinea pig ileum and human colon using fluorescence immunohistochemistry and RT-PCR in human colon. Double labelling using antibodies against neurochemical markers was used to identify neuron subytpes bearing M1r. M1r immunoreactivity (IR) was present on neurons in the myenteric and submucosal ganglia. The two antibodies gave similar M1r-IR patterns and M1r-IR was abolished upon antibody preabsorption. M1r-IR was present on cholinergic and nNOS-IR nerve cell bodies in both guinea pig and human myenteric neurons. Presynaptic M1r-IR was present on NOS-IR and VAChT-IR nerve fibres in the circular muscle in the human colon. In the submucosal ganglia, M1r-IR was present on a population of neurons that contained cChAT-IR, but did not contain NPY-IR or calretinin-IR. M1r-IR was present on endothelial cells of blood vessels in the submucosal plexus. The localisation of M1r-IR in the guinea pig and human ENS shown in this study agrees with physiological studies. M1r-IR in cholinergic and nitrergic neurons and nerve fibres indicate that M1rs have a role in both cholinergic and nitrergic transmission. M1r-IR present in submucosal neurons suggests a role in mediating acetylcholine's effect on submucosal sensory and secretomotor/vasodilator neurons. M1r-IR present on blood vessel endothelial cells suggests that M1rs may also mediate acetylcholine's direct effect on vasoactivation.

  13. Salinity Responses of Grafted Grapevines: Effects of Scion and Rootstock Genotypes

    Directory of Open Access Journals (Sweden)

    Nuray SIVRITEPE

    2010-12-01

    Full Text Available Two-year-old Sultana and Mke vines (Vitis vinifera L. grafted onto Rupestris du Lot (Vitis rupestris Scheele and 110 R (Vitis berlandieri Vitis rupestris were grown in soil, sand, sphagnum peat and farmyard manure mixture (2:1:1:1 v/v irrigated with 0.3, 2.7 and 5.45 dS m-1 NaCl solutions for a period of 60 days. Biomass accumulation, relative chlorophyll content, leaf water potential, stomatal conductance and transpiration were significantly reduced by salinity in all graft combinations. The inhibiting effect of salinity on growth varied according to the characteristics of the scion genotype and the level of salinity. The results imply the predominance of the scion genotype in determining variation in the leaf-level physiological characteristics of grafted vines because stomatal conductance and transpiration were higher in Sultana than in Mke at the same leaf water potential and the level of salinity, regardless of the rootstock genotype. NaCl treatments did not affect leaf Cu concentration while inducing significant Na, K, Ca, N, P, Mg, Fe, Mn and Zn elevations in the leaves of all scion/rootstock combinations. While salinity caused an increase in N content and a decrease in K content in the roots of all graft combinations, it had no influence on Ca, P, Cu and Zn concentrations. In contrast to the Sultana grafted vines, NaCl salinity led to a decrease in Mg, Fe and Mn concentrations in the roots of Mke grafted vines. Nevertheless, ion accumulation in leaves and roots of grafted vines under saline or non-saline conditions was controlled predominantly by the genotype of the scion. In response to salinity, Sultana grafts accumulated higher amounts of ions in their leaves than in their roots. However, in Mke, higher ion concentrations were seen in the roots. Therefore, the increase in the transport of inorganic ions up to the leaves seems to be the major component of osmotic adjustment in salt-stressed Sultana vines.

  14. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    Energy Technology Data Exchange (ETDEWEB)

    Zhirnov, O.P., E-mail: zhirnov@inbox.ru [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Manykin, A.A. [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Rossman, J.S. [School of Biosciences, University of Kent, Canterbury CT27NJ (United Kingdom); Klenk, H.D. [Institute of Virology, Philipps University, Marburg 35037 (Germany)

    2016-05-15

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  15. FRET-Based Detection of M1 Muscarinic Acetylcholine Receptor Activation by Orthosteric and Allosteric Agonists

    Science.gov (United States)

    Markovic, Danijela; Holdich, Jonathan; Al-Sabah, Suleiman; Mistry, Rajendra; Krasel, Cornelius; Mahaut-Smith, Martyn P.; Challiss, R. A. John

    2012-01-01

    Background and Objective Muscarinic acetylcholine receptors (mAChRs) are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational changes in the receptor remain unclear. To gain further insight into the actions of mAChR agonists, we have developed a fluorescently tagged M1 mAChR that reports ligand-induced conformational changes in real-time by changes in Förster resonance energy transfer (FRET). Methods Variants of CFP and YFP were inserted into the third intracellular loop and at the end of the C-terminus of the mouse M1 mAChR, respectively. The optimized FRET receptor construct (M1-cam5) was expressed stably in HEK293 cells. Results The variant CFP/YFP-receptor chimera expressed predominantly at the plasma membrane of HEK293 cells and displayed ligand-binding affinities comparable with those of the wild-type receptor. It also retained an ability to interact with Gαq/11 proteins and to stimulate phosphoinositide turnover, ERK1/2 phosphorylation and undergo agonist-dependent internalization. Addition of the full agonist methacholine caused a reversible decrease in M1 FRET (FEYFP/FECFP) that was prevented by atropine pre-addition and showed concentration-dependent amplitude and kinetics. Partial orthosteric agonists, arecoline and pilocarpine, as well as allosteric agonists, AC-42 and 77-LH-28-1, also caused atropine-sensitive decreases in the FRET signal, which were smaller in amplitude and significantly slower in onset compared to those evoked by methacholine. Conclusion The M1 FRET-based receptor chimera reports that allosteric and orthosteric agonists induce similar conformational changes in the third intracellular loop and/or C-terminus, and should prove to be a valuable molecular reagent for

  16. FRET-based detection of M1 muscarinic acetylcholine receptor activation by orthosteric and allosteric agonists.

    Directory of Open Access Journals (Sweden)

    Danijela Markovic

    Full Text Available BACKGROUND AND OBJECTIVE: Muscarinic acetylcholine receptors (mAChRs are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational changes in the receptor remain unclear. To gain further insight into the actions of mAChR agonists, we have developed a fluorescently tagged M(1 mAChR that reports ligand-induced conformational changes in real-time by changes in Förster resonance energy transfer (FRET. METHODS: Variants of CFP and YFP were inserted into the third intracellular loop and at the end of the C-terminus of the mouse M(1 mAChR, respectively. The optimized FRET receptor construct (M(1-cam5 was expressed stably in HEK293 cells. RESULTS: The variant CFP/YFP-receptor chimera expressed predominantly at the plasma membrane of HEK293 cells and displayed ligand-binding affinities comparable with those of the wild-type receptor. It also retained an ability to interact with Gα(q/11 proteins and to stimulate phosphoinositide turnover, ERK1/2 phosphorylation and undergo agonist-dependent internalization. Addition of the full agonist methacholine caused a reversible decrease in M(1 FRET (F(EYFP/F(ECFP that was prevented by atropine pre-addition and showed concentration-dependent amplitude and kinetics. Partial orthosteric agonists, arecoline and pilocarpine, as well as allosteric agonists, AC-42 and 77-LH-28-1, also caused atropine-sensitive decreases in the FRET signal, which were smaller in amplitude and significantly slower in onset compared to those evoked by methacholine. CONCLUSION: The M(1 FRET-based receptor chimera reports that allosteric and orthosteric agonists induce similar conformational changes in the third intracellular loop and/or C-terminus, and should prove to be a

  17. Probing of the location of the allosteric site on m1 muscarinic receptors by site-directed mutagenesis.

    Science.gov (United States)

    Matsui, H; Lazareno, S; Birdsall, N J

    1995-01-01

    In an attempt to locate the allosteric site on muscarinic receptors to which gallamine binds, 21 residues in the putative external loops and loop/transmembrane helix interfaces have been mutated to alanine. These residues are conserved in mammalian m1-m5 receptors. All mutant receptors can be expressed in COS-7 cells at high levels and appear to be functional, in that acetylcholine binding is sensitive to GTP. The gallamine binding site does not appear to involve the first, second, and most of the third extracellular loops. Tryptophan-400 and -101 inhibit gallamine binding when mutated to alanine or to phenylalanine and may form part of the allosteric site. Several mutations also affect antagonist binding. Surprisingly, tryptophan-91, a residue conserved in monoamine and peptide receptors, is important for antagonist binding. This residue, present in the middle of the first extracellular loop, may have a structural role in many G protein-coupled receptors. Antagonist binding is also affected by mutations of tryptophan-101 and tyrosine-404 to alanine or phenylalanine. In a helical wheel model, trytophan-101 and tyrosine-404, in conjunction with serine-78, aspartate-105, and tyrosine-408, form a cluster of residues that have been reported to affect antagonist binding when mutated, and they may therefore be part of the antagonist binding site. It is suggested that the allosteric site may be located close to and just extracellular to the antagonist binding site. The binding of methoctramine, an antagonist with allosteric properties, is not substantially affected by mutations at tryptophan-91, -101, and -400 and tyrosine-404, and thus these amino acids are not important for its binding. The binding of himbacine, another antagonist with allosteric properties, is affected by these mutations but in a manner different from that of gallamine or competitive antagonists. It has not been possible to determine whether methoctramine and himbacine bind exclusively to the

  18. The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma

    DEFF Research Database (Denmark)

    Rogers, A J; Brasch-Andersen, C; Ionita-Laza, I;

    2009-01-01

    : To explore the joint interactive effects of GSTM1 copy number and tobacco smoke exposure on the development of asthma and asthma-related phenotypes in a family-based cohort of childhood asthmatics. METHODS: We performed quantitative PCR-based genotyping for GSTM1 copy number in children of self......BACKGROUND: The glutathione S-transferase M1 (GSTM1)-null variant is a common copy number variant associated with adverse pulmonary outcomes, including asthma and airflow obstruction, with evidence of important gene-by-environment interactions with exposures to oxidative stress. OBJECTIVE......-reported white ancestry with mild to moderate asthma in the Childhood Asthma Management Program. Questionnaire data regarding intrauterine (IUS) and post-natal, longitudinal smoke exposure were available. We performed both family-based and population-based tests of association for the interaction between GSTM1...

  19. Genotyping panel for assessing response to cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Hampel Heather

    2008-06-01

    Full Text Available Abstract Background Variants in numerous genes are thought to affect the success or failure of cancer chemotherapy. Interindividual variability can result from genes involved in drug metabolism and transport, drug targets (receptors, enzymes, etc, and proteins relevant to cell survival (e.g., cell cycle, DNA repair, and apoptosis. The purpose of the current study is to establish a flexible, cost-effective, high-throughput genotyping platform for candidate genes involved in chemoresistance and -sensitivity, and treatment outcomes. Methods We have adopted SNPlex for genotyping 432 single nucleotide polymorphisms (SNPs in 160 candidate genes implicated in response to anticancer chemotherapy. Results The genotyping panels were applied to 39 patients with chronic lymphocytic leukemia undergoing flavopiridol chemotherapy, and 90 patients with colorectal cancer. 408 SNPs (94% produced successful genotyping results. Additional genotyping methods were established for polymorphisms undetectable by SNPlex, including multiplexed SNaPshot for CYP2D6 SNPs, and PCR amplification with fluorescently labeled primers for the UGT1A1 promoter (TAnTAA repeat polymorphism. Conclusion This genotyping panel is useful for supporting clinical anticancer drug trials to identify polymorphisms that contribute to interindividual variability in drug response. Availability of population genetic data across multiple studies has the potential to yield genetic biomarkers for optimizing anticancer therapy.

  20. Differential activation of dendritic cells by Mycobacterium tuberculosis Beijing genotype.

    Science.gov (United States)

    Reyes-Martínez, Juana Elizabeth; Nieto-Patlán, Erik; Nieto-Patlán, Alejandro; Gonzaga-Bernachi, Job; Santos-Mendoza, Teresa; Serafín-López, Jeanet; Chávez-Blanco, Alma; Sandoval-Montes, Claudia; Flores-Romo, Leopoldo; Estrada-Parra, Sergio; Estrada-García, Iris; Chacón-Salinas, Rommel

    2014-01-01

    Mycobacterium tuberculosis (Mtb) inhibits dendritric cells (DC) function in order to delay T cell response. Furthermore, there is increasing evidence that genetic diversity of Mtb strains can affect their interaction with the immune system. Beijing genotype has attracted attention because of its high prevalence and multi-drug resistance. Although it is known that this genotype is hypervirulent and differentially activates macrophages when compared to other genotypes, little is known about its interaction with DC. In order to address this issue, murine bone marrow derived DC (BMDC) were stimulated with soluble extracts (SE) from BCG, H37Rv, Canetti and Beijing genotypes. We observed that unlike other mycobacteria strains, SE-Beijing was unable to induce maturation of DC as assessed by cell surface MHC-II expression. DC stimulated with SE-Beijing failed to produce IL-12 and TNF-α, but did secrete IL-10. Interestingly, SE-Beijing induced CCR7 and PDL-1 on BMDC, but did not induce the expression of CD86. When BMDC stimulated with SE-Beijing were used to activate CD4+ cells they were unable to induce a Th1 response when compared with less virulent genotypes. These results indicate that Beijing is able to modulate DC activation and function, which may be related to the pathogenesis induced by this genotype.

  1. New probe of M1 and E1 strengths in GDR regions

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, T. [Japan Atomic Energy Agency and National Astronomical Observatory in Japan (Japan); Ogata, K. [RCNP, Osaka University (Japan); Miyamoto, S.; Mochizuki, T.; Horikawa, K.; Amano, S. [University of Hyogo (Japan); Imazaki, K.; Li, D.; Izawa, Y. [Institute for Laser Technology (Japan); Chiba, S. [Tokyo Institute of Technology (Japan)

    2014-05-02

    The M1 strengths (or level density of 1{sup +} states) are of importance for estimation of interaction strengths between neutrinos and nuclei for the study of the supernova neutrino-process. In 1957, Agodi predicted theoretically angular distribution of neutrons emitted from states excited via dipole transitions with linearly polarized gamma-ray beam at the polar angle of θ=90° should be followed by a simple function, a + b cos(2φ), where φ, is azimuthal angel. However, this theoretical prediction has not been verified over the wide mass region except for light nuclei as deuteron. We have measured neutron angular distributions with (polarized gamma, n) reactions on Au, Nal, and Cu. We have verified the Agodi's prediction for the first time over the wide mass region. This suggests that (polarized gamma, n) reactions may be useful tools to study M1 strengths in giant resonance regions.

  2. Design and optimization of selective azaindole amide M1 positive allosteric modulators.

    Science.gov (United States)

    Davoren, Jennifer E; O'Neil, Steven V; Anderson, Dennis P; Brodney, Michael A; Chenard, Lois; Dlugolenski, Keith; Edgerton, Jeremy R; Green, Michael; Garnsey, Michelle; Grimwood, Sarah; Harris, Anthony R; Kauffman, Gregory W; LaChapelle, Erik; Lazzaro, John T; Lee, Che-Wah; Lotarski, Susan M; Nason, Deane M; Obach, R Scott; Reinhart, Veronica; Salomon-Ferrer, Romelia; Steyn, Stefanus J; Webb, Damien; Yan, Jiangli; Zhang, Lei

    2016-01-15

    Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies.

  3. IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Serkan I. Göktuna

    2014-06-01

    Full Text Available The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC therapy.

  4. Extended M1 sum rule for excited symmetric and mixed-symmetry states in nuclei

    CERN Document Server

    Smirnova, N A; Leviatan, A; Ginocchio, J N; Fransen, C

    2002-01-01

    A generalized M1 sum rule for orbital magnetic dipole strength from excited symmetric states to mixed-symmetry states is considered within the proton-neutron interacting boson model of even-even nuclei. Analytic expressions for the dominant terms in the B(M1) transition rates from the first and second $2^+$ states are derived in the U(5) and SO(6) dynamic symmetry limits of the model, and the applicability of a sum rule approach is examined at and in-between these limits. Lastly, the sum rule is applied to the new data on mixed-symmetry states of 94Mo and a quadrupole d-boson ratio $nd(0^+_1)/nd(2^+_2) \\approx 0.6$ is obtained in a largely parameter-independent way

  5. M=1 and 2 gravitational instabilities in gaseous disks; 1, diffuse gas

    CERN Document Server

    Junqueira, S

    1996-01-01

    We report the results of self-gravitating simulations of spiral galaxies, modeled by stellar and gaseous components, developed to investigate in particular the role of dissipation in the evolution of galaxy disks. The gas disk is simulated by the Beam-Scheme method, where it is considered as a self-gravitating fluid. The results suggest that the gravitational coupling between the stars and gas plays a fundamental role in the formation and dissolution of stellar bars, depending on the gaseous mass concentration and on the degree of dissipation. In addition we remark that initially concentrated gas disks can be unstable to the one-armed (m=1) spiral perturbations, which may explain the lopsided features observed in the gas distribution of the late-type isolated galaxies. The development of the m=1 feature slows down the radial gas flows towards the center, since the large-scale gravity torques are then much weaker.

  6. Cholinergic impact on neuroplasticity drives muscarinic M1 receptor mediated differentiation into neurons.

    Science.gov (United States)

    Benninghoff, Jens; Rauh, Werner; Brantl, Victor; Schloesser, Robert J; Moessner, Rainald; Möller, Hans-Jürgen; Rujescu, Dan

    2013-04-01

    Increasing evidence indicates that canonical neurotransmitters act as regulatory signals during neuroplasticity. Here, we report that muscarinic cholinergic neurotransmission stimulates differentiation of adult neural stem cells in vitro. Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in culture with basic fibroblast growth factor (BFGF) and epidermal growth factor (EGF). Carbachol (CCh), an analog of acetylcholine (ACh) significantly enhanced de novo differentiation into neurons on bFGF- and EGF-deprived stem cells as shown by the percentage of TUJ1 positive cells. By contrast, pirenzepine (PIR), a muscarinic M1 receptor antagonist, reduced the generation of neurons. Activation of cholinergic signaling drives the de novo differentiation of uncommitted stem cells into neurons. These effects appear to be predominantly mediated via the muscarinic M1 receptor subtype.

  7. Commercial scale demonstration enhanced oil recovery by miceller-polymer flooding. M-1 project: facilities report

    Energy Technology Data Exchange (ETDEWEB)

    Knight, B.L. (ed.)

    1977-04-01

    ERDA and Marathon Oil Company contracted together for a commercial scale demonstration of enhanced oil recovery by the Maraflood (TM) oil recovery process. This M-1 Project is located within Sections 15, 16, 21 and 22, T6N, R13W, Crawford County, Illinois, encompassing approximately 407 acres of Robinson Sand reservoir developed in the first decade of the century. The area covers portions of several waterfloods developed on 10-acre spacing in the 1950's that were approaching their economic limit. This report describes all M-1 Project facilities, how they were prepared or constructed, their purpose and how they operate: (1) wells (drilling and completion); (2) production facility; (3) injection facility; and (4) various service systems required during project development and/or operation. (48 fig, 7 tables) (DLC).

  8. Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages

    Directory of Open Access Journals (Sweden)

    Sanjima Pal

    2016-06-01

    Full Text Available Any chronic, inflammatory, autoimmune disease (e.g. arthritis associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues. Despite of few studies demonstrating efficiency of Sulforaphane (SFN in suppressing arthritis associated collagen restricted T cells or fibroblasts, its effects on macrophage polarity and plasticity are less understood. Recently, we reported regulation of phenotypic and functional switching by SFN in induced and spontaneously differentiating human monocytes [1]. Here, flow cytometry, western blot and ELISA derived data demonstrated that SFN inhibited in vitro inflammatory responses developed by soluble human collagens (I–IV induced auto-reactive M1 type monocyte/macrophage model.

  9. THE BULK INPUT M[X]/M/1 QUEUE WITH WORKING VACATIONS

    Institute of Scientific and Technical Information of China (English)

    Xiuli XU; Mingxin LIU; Xiaohua ZHAO

    2009-01-01

    In this paper, we analyze a bulk input M[X]/M/1 queue with multiple working vacations. A quasi upper triangle transition probability matrix of two-dimensional Markov chain in this model is obtained, and with the matrix analysis method, highly complicated probability generating function(PGF) of the stationary queue length is firstly derived, from which we got the stochastic decomposition result for the stationary queue length which indicates the evident relationship with that of the classical M[X]/M/1 queue without vacation. It is important that we find the upper and the lower bounds of the stationary waiting time in the Laplace transform order using the properties of the conditional Erlang distribution. Furthermore, we gain the mean queue length and the upper and the lower bounds of the mean waiting time.

  10. Transforming microbial genotyping: a robotic pipeline for genotyping bacterial strains.

    Directory of Open Access Journals (Sweden)

    Brian O'Farrell

    Full Text Available Microbial genotyping increasingly deals with large numbers of samples, and data are commonly evaluated by unstructured approaches, such as spread-sheets. The efficiency, reliability and throughput of genotyping would benefit from the automation of manual manipulations within the context of sophisticated data storage. We developed a medium- throughput genotyping pipeline for MultiLocus Sequence Typing (MLST of bacterial pathogens. This pipeline was implemented through a combination of four automated liquid handling systems, a Laboratory Information Management System (LIMS consisting of a variety of dedicated commercial operating systems and programs, including a Sample Management System, plus numerous Python scripts. All tubes and microwell racks were bar-coded and their locations and status were recorded in the LIMS. We also created a hierarchical set of items that could be used to represent bacterial species, their products and experiments. The LIMS allowed reliable, semi-automated, traceable bacterial genotyping from initial single colony isolation and sub-cultivation through DNA extraction and normalization to PCRs, sequencing and MLST sequence trace evaluation. We also describe robotic sequencing to facilitate cherrypicking of sequence dropouts. This pipeline is user-friendly, with a throughput of 96 strains within 10 working days at a total cost of 200,000 items were processed by two to three people. Our sophisticated automated pipeline can be implemented by a small microbiology group without extensive external support, and provides a general framework for semi-automated bacterial genotyping of large numbers of samples at low cost.

  11. Modulating activity of M1 receptor to the reaction of ileal smooth muscle.

    Science.gov (United States)

    Glaza, Izabela; Szadujkis-Szadurski, Leszek; Szadujkis-Szadurski, Rafał; Gajdus, Marta; Olkowska, Joanna

    2011-08-03

    The subject of the study was determination of the effect of drugs on ileal smooth muscle contraction induced by activation of M(1) type muscarinic receptors. Drugs that have an effect on muscarinic receptors are divided to agonists, with close ties to the receptor and high internal activity and antagonists, with no internal activity. Conducted experiments tested interactions between a broad-spectrum agonist of muscarinic receptors, carbachol and a selective muscarinic receptor antagonist of M(1) type, pirenzepine. Testing was conducted on tissues isolated from rat's intestine. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg). Concentration-effect curves were determined with the use of cumulated concentration method, in accordance with the van Rossum method (1963) in Kenakin modification (2006). The purpose of the study was determination of concentration-effect curves for carbachol. This curve was compared with the curve of receptor occupation depending on concentration of this drug. Based on concentration-effect curves, the average value of EC(50) was calculated for carbachol, amounting to 2.44×10(-6) [M/l]. The results confirmed that atropine is effective in stopping contractions caused by carbachol, meeting the conditions of competitive antagonists. Atropine caused the shift of curves for carbachol to the right. Pirenzepine, selectively blocking muscarinic receptors of M(1) type gave similar results. It was proved that in the preparation of gastric fundus smooth muscle, M(1) type receptors occur not only presynaptically, but also postsynaptically.

  12. Modulating activity of M1 receptor to the reaction of ileal smooth muscle

    Directory of Open Access Journals (Sweden)

    Izabela Glaza

    2011-08-01

    Full Text Available Background:The subject of the study was determination of the effect of drugs on ileal smooth muscle contraction induced by activation of M1 type muscarinic receptors. Drugs that have an effect on muscarinic receptors are divided to agonists, with close ties to the receptor and high internal activity and antagonists, with no internal activity. Conducted experiments tested interactions between a broad-spectrum agonist of muscarinic receptors, carbachol and a selective muscarinic receptor antagonist of M1 type, pirenzepine.Material/Methods:Testing was conducted on tissues isolated from rat’s intestine. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg. Concentration-effect curves were determined with the use of cumulated concentration method, in accordance with the van Rossum method (1963 in Kenakin modification (2006.Results:The purpose of the study was determination of concentration-effect curves for carbachol. This curve was compared with the curve of receptor occupation depending on concentration of this drug. Based on concentration-effect curves, the average value of EC50 was calculated for carbachol, amounting to 2.44×10–6 [M/l].Conclusions:The results confirmed that atropine is effective in stopping contractions caused by carbachol, meeting the conditions of competitive antagonists. Atropine caused the shift of curves for carbachol to the right. Pirenzepine, selectively blocking muscarinic receptors of M1 type gave similar results. It was proved that in the preparation of gastric fundus smooth muscle, M1 type receptors occur not only presynaptically, but also postsynaptically.

  13. Role of M1 receptor in regulation of gastric fundus smooth muscle contraction

    Directory of Open Access Journals (Sweden)

    Marta Gajdus

    2011-09-01

    Full Text Available Background:The subject of this study is determination of the influence of drugs on gastric fundus smooth muscle contraction induced by activation of muscarinic receptors M1. Experiments tested interactions between a receptor agonist, carbachol and muscarinic receptor antagonists, atropine and pirenzepine.Material/Methods:Testing was conducted on tissues isolated from rat’s stomach. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg. The stomach was dissected, and later the gastric fundus was isolated. Tissue was placed in a dish for insulated organs with 20 ml in capacity, filled with Krebs fluid. Results contained in the study are average values ± SE. In order to determine statistical significance, the principles of receptor theory were used (Kenakin modification.Results:According to tests, carbachol, in concentrations ranging between 10–8 M to 10–4 M, in a dosage-dependent way induces gastric fundus smooth muscle contraction. Presented results indicate that carbachol meets the conditions posed to full agonists. On the other hand, atropine, a non-selective muscarinic receptor antagonist, causes a concentration-dependent shift of concentration-effect curve (for carbachol to the right, maintaining maximum reaction. According to analysis of the curve determined, we can deduce that atropine meets the conditions posed to competitive antagonists. The use of pirenzepine, a competitive receptor agonist M1, causes shift of concentration-effect curve (for carbachol to the right, maintaining maximum reaction.Conclusions:From the testing conducted on the preparation of the gastric fundus we can deduce that atropine causes shift of concentration-effect curves for carbachol to the right. A similar effect is released by pirenzepine, selectively blocking muscarinic receptors of M1 type. The results indicate that in the preparation of the gastric fundus smooth muscle, M1 type

  14. Role of M1 receptor in regulation of gastric fundus smooth muscle contraction.

    Science.gov (United States)

    Gajdus, Marta; Szadujkis-Szadurska, Katarzyna; Szadujkis-Szadurski, Leszek; Glaza, Izabela; Szadujkis-Szadurski, Rafał; Olkowska, Joanna

    2011-09-14

    The subject of this study is determination of the influence of drugs on gastric fundus smooth muscle contraction induced by activation of muscarinic receptors M1. Experiments tested interactions between a receptor agonist, carbachol and muscarinic receptor antagonists, atropine and pirenzepine. Testing was conducted on tissues isolated from rat's stomach. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg). The stomach was dissected, and later the gastric fundus was isolated. Tissue was placed in a dish for insulated organs with 20 ml in capacity, filled with Krebs fluid. Results contained in the study are average values ± SE. In order to determine statistical significance, the principles of receptor theory were used (Kenakin modification). According to tests, carbachol, in concentrations ranging between 10(-8) M to 10(-4) M, in a dosage-dependent way induces gastric fundus smooth muscle contraction. Presented results indicate that carbachol meets the conditions posed to full agonists. On the other hand, atropine, a non-selective muscarinic receptor antagonist, causes a concentration-dependent shift of concentration-effect curve (for carbachol) to the right, maintaining maximum reaction. According to analysis of the curve determined, we can deduce that atropine meets the conditions posed to competitive antagonists. The use of pirenzepine, a competitive receptor agonist M1, causes shift of concentration-effect curve (for carbachol) to the right, maintaining maximum reaction. From the testing conducted on the preparation of the gastric fundus we can deduce that atropine causes shift of concentration-effect curves for carbachol to the right. A similar effect is released by pirenzepine, selectively blocking muscarinic receptors of M1 type. The results indicate that in the preparation of the gastric fundus smooth muscle, M1 type receptors occur also postsynaptically.

  15. "5M1E"法在生产管理中的运用

    Institute of Scientific and Technical Information of China (English)

    刘秋香

    2010-01-01

    人(man)、机械(machine)、材料(material)、方法(method)、环境(enviroment)、管理(manage)这几个主要环节实行全面质量管理,称为"5M1E"法.在生产管理中应用该法,可以达到提升人品质、提升产品品质,提高员工士气.

  16. Radiationless transitions to atomic M 1,2,3 shells - Results of relativistic theory

    Science.gov (United States)

    Chen, M. H.; Crasemann, B.; Mark, H.

    1983-01-01

    Radiationless transitions filling vacancies in atomic M1, M2, and M3 subshells have been calculated relativistically with Dirac-Hartree-Slater wave functions for ten elements with atomic numbers 67-95. Results are compared with those of nonrelativistic calculations and experiment. Relativistic effects are found to be significant. Limitations of an independent-particle model for the calculation of Coster-Kronig rates are noted.

  17. Study of Mutagenic Effects of M1 Generation of Maize Seeds Irradiated by Heavy Ions

    Institute of Scientific and Technical Information of China (English)

    LUOHong-bing; ZHAOKui; GUOJi-yu; SUILi; NIMei-nan; MEIJun-ping; LUXiu-qin; ZHOUPing; KONGFu-quan; ZHANGGen-fa

    2003-01-01

    In order to study M1 biological effects induced by heavy ion irradiation on maize seeds, the embryos of dry maize seeds are irradiated with 7Li and 12C ions. The experiment is performed at the heavy ion scanning tube of the HI-13 tandem accelerator. The beam goes through a thickness of 25μm. Then the maize seeds are irradiated in the air uniformly.

  18. Effects of elevated CO2 and plant genotype on interactions among cotton, aphids and parasitoids

    Institute of Scientific and Technical Information of China (English)

    Yu-Cheng Sun; Li Feng; Feng Gao; Feng Ge

    2011-01-01

    Effects of CO2 level (ambient vs.elevated) on the interactions among three cotton (Gossypium hirsutum) genotypes,the cotton aphid (Aphis gossypii Glover),and its hymenoptera parasitoid (Lysiphlebiajaponica Ashrnead) were quantified.It was hypothesized that aphid-parasitoid interactions in crop systems may be altered by elevated CO2,and that the degree of change is influenced by plant genotype.The cotton genotypes had high (M9101),medium (HZ401) and low (ZMS 13) gossypol contents,and the response to elevated CO2 was genotype-specific.Elevated CO2 increased the ratio of total non-structural carbohydrates to nitrogen (TNC:N) in the high-gossypol genotype and the mediumgossypol genotype.For all three genotypes,elevated CO2 had no effect on concentrations of gossypol and condensed tannins.A.gossypii fitness declined when aphids were reared on the high-gossypol genotype versus the low-gossypol genotype under elevated CO2.Furthermore,elevated CO2 decreased the developmental time of L.japonica associated with the high-gossypol genotype and the low-gossypol genotype,but did not affect parasitism or emergence rates.Our study suggests that the abundance of A.gossypii on cotton will not be directly affected by increases in atmospheric CO2.We speculate that A.gossypii may diminish in pest status in elevated CO2 and high-gossypol genotype environments because of reduced fitness to the high-gossypol genotype and shorter developmental time of L.japonica.

  19. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Marcin Poreba

    Full Text Available BACKGROUND: Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. METHODOLOGY/PRINCIPAL FINDINGS: To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. CONCLUSIONS/SIGNIFICANCE: This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment.

  20. Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

    Science.gov (United States)

    Poreba, Marcin; McGowan, Sheena; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Gardiner, Donald L.; Whisstock, James C.; To, Joyce; Salvesen, Guy S.; Dalton, John P.; Drag, Marcin

    2012-01-01

    Background Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. Methodology/Principal Findings To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. Conclusions/Significance This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment. PMID:22359643

  1. A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages

    Science.gov (United States)

    Deng, Huimin; Li, Zhengchao; Tan, Yafang; Guo, Zhaobiao; Liu, Yangyang; Wang, Ye; Yuan, Yuan; Yang, Ruifu; Bi, Yujing; Bai, Yang; Zhi, Fachao

    2016-01-01

    Commensal Bacteroides fragilis possesses immune-regulatory characteristics. Consequently, it has been proposed as a potential novel probiotic because of its therapeutic effects on immune imbalance, mental disorders and inflammatory diseases. Macrophages play a central role in the immune response, developing either a classical-M1 or an alternative-M2 phenotype after stimulation with various signals. The interactions between macrophages and B. fragilis, however, remain to be defined. Here, a new isolate of B. fragilis, ZY-312, was shown to possess admirable properties, including tolerance to simulated gastric fluid, intestinal fluid and ox bile, and good safety (MOI = 100, 200) and adherent ability (MOI = 100) to LoVo cells. Isolate ZY-312 cell lysate promoted phagocytosis of fluorescent microspheres and pathogenic bacteria in bone marrow-derived macrophage (BMDM) cells. Gene expression of IL-12, iNOS and IL-1β in BMDM cells was increased after treatment with ZY-312, indicating the induction of M1 macrophages, consistent with enhanced secretion of NO. Cell surface expression of CD80 and CD86 was also increased. This study is the first to demonstrate that B. fragilis enhances the phagocytic functions of macrophages, polarising them to an M1 phenotype. Our findings provide insight into the close relationship between B. fragilis and the innate immune system. PMID:27381366

  2. The mechanism of the anticancer function of M1 macrophages and their use in the clinic

    Institute of Scientific and Technical Information of China (English)

    Xing-Qing Pan

    2012-01-01

    M1-type macrophages are capable of inducing lysis in various types of cancer cells,but the mechanism of action is unclear.It has been noted that an "unknown protein" produced together with protease by activated macrophages is responsible for this action.Activated M1 macrophages have been recently reported to produce family 18 chitinases,all of which have been named chitotriosidase.Our experiments have demonstrated that family 18 chitinases work together with proteases and can damage various cancer cells both in vitro and in vivo.Thus,in this article,we suggest that the 50-kDa chitotriosidase is the reported "unknown protein".In addition,we discuss how to properly stimulate activated M1 macrophages to produce 50-kDa chitotriosidases and proteases for destroying cancer cells.Because family 19 chitinase has recently been reported to kill cancer cells,we also discuss the possibility of directly using human family 18 chitotriosidase and the humanized plant family 19 chitinase for cancer treatment.

  3. The detection of C60 in the well-characterized planetary nebula M1-11

    CERN Document Server

    Otsuka, Masaaki; Hyung, S; Sargent, B A; Meixner, M; Tajitsu, A; Yanagisawa, K

    2013-01-01

    We performed multiwavelength observations of the young planetary nebula (PN) M1-11 and obtained its elemental abundances, dust mass, and the evolutionary status of the central star. The AKARI/IRC, VLT/VISIR, and Spitzer/IRS spectra show features due to carbon-rich dust, such as the 3.3, 8.6, and 11.3 um features due to polycyclic aromatic hydrocarbons (PAHs), a smooth continuum attributable to amorphous carbon, and the broad 11.5 and 30 um features often ascribed to SiC and MgS, respectively. We also report the presence of an unidentified broad feature at 16-22 um, similar to the feature found in Magellanic Cloud PNe with either C-rich or O-rich gas-phase compositions. We identify for the first time in M1-11 spectral lines at 8.5 (blended with PAH), 17.3, and 18.9 um that we attribute to the C60 fullerene. This identification is strengthened by the fact that other Galactic PNe in which fullerenes are detected, have similar central stars, similar gas-phase abundances, and a similar dust composition to M1-11. T...

  4. Surface Termination of M1 Phase and Rational Design of Propane Ammoxidation Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Guliants, Vadim

    2015-02-16

    This final report describes major accomplishments in this research project which has demonstrated that the M1 phase is the only crystalline phase required for propane ammoxidation to acrylonitrile and that a surface monolayer terminating the ab planes of the M1 phase is responsible for their activity and selectivity in this reaction. Fundamental studies of the topmost surface chemistry and mechanism of propane ammoxidation over the Mo-V-(Te,Sb)-(Nb,Ta)-O M1 and M2 phases resulted in the development of quantitative understanding of the surface molecular structure – reactivity relationships for this unique catalytic system. These oxides possess unique catalytic properties among mixed metal oxides, because they selectively catalyze three alkane transformation reactions, namely propane ammoxidation to acrylonitrile, propane oxidation to acrylic acid and ethane oxidative dehydrogenation, all of considerable economic significance. Therefore, the larger goal of this research was to expand this catalysis to other alkanes of commercial interest, and more broadly, demonstrate successful approaches to rational design of improved catalysts that can be applied to other selective (amm)oxidation processes.

  5. Aflatoxin M1 in raw milk in Qazvin Province, Iran: a seasonal study.

    Science.gov (United States)

    Fallah, Aziz A; Barani, Afshin; Nasiri, Zeinab

    2015-01-01

    Occurrence of aflatoxin M1 (AFM1) was determined in 254 samples of raw milk obtained from dairy cow farms of Qazvin Province, Iran. Aflatoxin M1 analysis was carried out by using the competitive enzyme-linked immunosorbent assay technique for screening and high-performance liquid chromatography with fluorescence detection for confirmatory purposes. The limit of detection and quantification of the confirmatory method were 0.003 and 0.01 µg/l, respectively. Aflatoxin M1 was detected in 204 analysed samples (80.3%), ranging from 0.011 to 0.321 μg/l, and 144 samples (56.7%) had levels above the Iranian national standard limit of 0.050 μg/l. Considering the seasonal variability, the occurrence and levels of AFM1 in samples obtained in winter were significantly higher (P < 0.05) than those obtained in summer. The results of this survey indicate the usefulness of a monitoring programme to supervise food safety for consumers.

  6. Enhanced Macrophage M1 Polarization and Resistance to Apoptosis Enable Resistance to Plague.

    Science.gov (United States)

    Pachulec, Emilia; Abdelwahed Bagga, Rym Ben; Chevallier, Lucie; O'Donnell, Hope; Guillas, Chloé; Jaubert, Jean; Montagutelli, Xavier; Carniel, Elisabeth; Demeure, Christian E

    2017-09-15

    Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined. SEG MPs exhibit a stronger bactericidal activity with higher nitric oxide production, a more proinflammatory polarized cytokine response, and a higher resistance to Y. pestis-induced apoptosis. This response was not specific to Y. pestis and involved a reduced sensitivity to M2 polarization/signal transducer and activator of transcription 6 activation and inhibition of caspase 8. The enhanced M1 profile was inducible in C57BL/6 MPs in vitro, and when transferred to susceptible C57BL/6 mice, these MPs significantly increased survival of bubonic plague. MPs can develop an enhanced functional profile beyond the prototypic M1, characterized by an even more potent proinflammatory response coordinated with resistance to killing. This programming plays a key role in the plague-resistance phenotype and may be similarly significant in other highly lethal infections, suggesting that orienting the MP response may represent a new therapeutic approach.

  7. Postmortem Changes in Pork Muscle Protein Phosphorylation in Relation to the RN Genotype

    DEFF Research Database (Denmark)

    Lametsch, René; Larsen, Martin Røssel; Essén-Gustavsson, Birgitta

    2011-01-01

    Postmortem changes in pork muscle protein phosphorylation in relation to the RN(-) genotype were investigated using one-dimensional gel electrophoresis and a phosphor specific staining. The phosphorylation levels of several protein bands were found to be affected by the RN(-) genotype and to chan...

  8. Bottom-up effects of plant genotype on aphids, ants, and predators.

    Science.gov (United States)

    Johnson, Marc T J

    2008-01-01

    Theory predicts that bottom-up ecological forces can affect community dynamics, but whether this extends to the effects of heritable plant variation on tritrophic communities is poorly understood. In a field experiment, I contrasted the effects of plant genotype (28 genotypes; 1064 plants), aphid density, and the presence/absence of mutualistic ants in affecting the per capita population growth of a specialist aphid herbivore, as well as the effects of plant genotype on the third trophic level. Plant genotype strongly affected aphid population growth rate, explaining 29% of the total variation in growth rate, whereas aphid density and ant-aphid interactions explained substantially less variation (Plant genotype also had direct and indirect effects on the third trophic level, affecting the abundance of aphid-tending ants and the richness of predators. Multiple regression identified several heritable plant traits that explained 49% of the variation in aphid growth rate and 30% of the variation in ant abundance among plant genotypes. These bottom-up effects of plant genotype on tritrophic interactions were independent of the effects of either initial aphid density or the presence/absence of mutualistic ants. This study shows that plant genotype can be one of the most important ecological factors shaping tritrophic communities.

  9. Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors

    NARCIS (Netherlands)

    Schueller, Ulrich; Zhao, Qing; Godinho, Susana A.; Heine, Vivi M.; Medema, Rene H.; Pellman, David; Rowitch, David H.

    2007-01-01

    The forkhead transcription factor FoxM1 has been reported to regulate, variously, proliferation and/or spindle formation during the G(2)/M transition of the cell cycle. Here we define specific functions of FoxM1 during brain development by the investigation of FoxM1 loss-of-function mutations in the

  10. Alcobaça allele and genotypic backgrounds affect yield and fruit shelf life of tomato hybrids O alelo alcobaça e o background genotípico afetam a produtividade e a conservação de híbridos de tomateiro

    Directory of Open Access Journals (Sweden)

    Túlio José Mendes Dias

    2003-01-01

    Full Text Available Post-harvest shelf life of tomato fruit may be increased by deploying mutant alleles which affect the natural ripening process and/or by a favorable genotypic background. Among the several ripening mutant genes, alcobaça (alc has proved to be highly efficient in increasing shelf life of commercial tomato fruits, especially in heterozygosis, a state at which no limiting deleterious effects upon fruit color occur. The effects of heterozygosity in the alcobaça locus (alc+/alc on yield and fruit quality traits of tomato hybrids with three genotypic backgrounds. We evaluated three pairs of hybrids obtained from crosses between the near-isogenic pollen source lines Flora-Dade (alc+/alc+ and TOM-559 (alc/alc, and three maternal lines (Stevens, NC-8276 and Piedmont. The six treatments were factorial combinations of two different status in the alc locus (alc+/alc and alc+/alc+ versus three different genotypic backgrounds (maternal lines. Fruits were harvested at the breaker stage of maturation and stored in shelves at 21ºC for 14 days. Yield and fruit quality traits were then evaluated. Regardless of the background, the alc allele in heterozygosis (alc+/alc did not interfere with the total yield, commercial yield, average mass per fruit, average mass per commercial fruit, fruit shape, or with fruit peduncular scar diameter. The alc+/alc genotype reduced the rate of firmness loss and delayed evolution of the red color of the fruit, thus contributing to an increase of the post-harvest shelf life for all three genotypic backgrounds.A vida de prateleira dos frutos de tomate pode ser extendida, seja empregando-se alelos mutantes que afetam o processo natural de amadurecimento, seja por meio de background genotípico favorável. O alelo alcobaça (alc em heterozigose tem-se mostrado bastante eficiente no sentido de prolongar o período de conservação dos frutos em pós-colheita, sem que ocorra prejuízo na coloração. Avaliaram-se os efeitos do alelo

  11. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  12. Glutathione S-transferases M1 and T1 polymorphisms and arsenic content in hair and urine in two ethnic clans exposed to indoor combustion of high arsenic coal in Southwest Guizhou, China

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Guo-fang; Guo, Wei-chao; Shen, Jian-hua [Chinese Academy of Sciences, Shanghai Institutes for Biological Sciences, Institute of Plant Physiology and Ecology, Shanghai (China); Du, Hui; Lu, Hong-chao; Kai, Jin-xiang; Zhou, Yun-shu [Prefecture Center for Disease Prevention and Control, Xingyi, Guizhou (China); Chen, Ji-gang [Municipal Center for Disease Prevention and Control, Shanghai (China); Zhang, Xin-jiang [Zunyi Medical College, Affiliated Hospital, Division of Dermatology, Zunyi, Guizhou (China); Lu, Da-ru [Fudan University, Institute of Genetics, School of Life Sciences, Shanghai (China); Golka, Klaus [Institute for Occupational Physiology at the University of Dortmund, Dortmund (Germany)

    2007-08-15

    A total of 2,402 cases of arsenic-related skin lesions (as of 2002) in a few villages of China's Southwest Guizhou Autonomous Prefecture represent a unique case of endemic arseniasis related with indoor combustion of high arsenic coal. A significant difference of skin lesion prevalence was observed between two clans of different ethnicities (Hmong and Han) in one of the hyperendemic villages in this prefecture. This study was focused on a possible involvement of GST T1 and M1 polymorphisms in risk modulation of skin lesions and in the body burden of As in this unique case of As exposure. GST T1 and M1 polymorphisms were genotyped by an allele-specific PCR-based procedure. Total As contents in hair and urine samples as well as environmental samples of the homes of the two ethnic clans were analyzed. No significant deviations in the population frequencies of GST T1 and M1 0/0 genotypes or their combination were recorded between diagnosed skin lesion patients and asymptomatic individuals in both clans. Significantly higher As contents in hair and urine were observed in GSTM1 0/0 carriers, not in GSTT1 0/0 carriers. After stratified by ethnicity and gender, a statistically significant association of the GSTM1 0/0 genotype and higher As content in hair was only confirmed in the subgroups of ethnic Han clan members and all male villagers, not in ethnic Hmong clan members or in females. GST T1 and M1 homozygous deletions were not associated with an increased susceptibility to skin lesions in long-term exposure to indoor combustion of high As coal. The polymorphic status at the locus of GSTM1 might modulate individual's body burden of total As in some Chinese ethnic groups. (orig.)

  13. Haplotypes versus genotypes on pedigrees

    Directory of Open Access Journals (Sweden)

    Kirkpatrick Bonnie B

    2011-04-01

    Full Text Available Abstract Background Genome sequencing will soon produce haplotype data for individuals. For pedigrees of related individuals, sequencing appears to be an attractive alternative to genotyping. However, methods for pedigree analysis with haplotype data have not yet been developed, and the computational complexity of such problems has been an open question. Furthermore, it is not clear in which scenarios haplotype data would provide better estimates than genotype data for quantities such as recombination rates. Results To answer these questions, a reduction is given from genotype problem instances to haplotype problem instances, and it is shown that solving the haplotype problem yields the solution to the genotype problem, up to constant factors or coefficients. The pedigree analysis problems we will consider are the likelihood, maximum probability haplotype, and minimum recombination haplotype problems. Conclusions Two algorithms are introduced: an exponential-time hidden Markov model (HMM for haplotype data where some individuals are untyped, and a linear-time algorithm for pedigrees having haplotype data for all individuals. Recombination estimates from the general haplotype HMM algorithm are compared to recombination estimates produced by a genotype HMM. Having haplotype data on all individuals produces better estimates. However, having several untyped individuals can drastically reduce the utility of haplotype data.

  14. Production of a monoclonal antibody against aflatoxin M1 and its application for detection of aflatoxin M1 in fortified milk

    Directory of Open Access Journals (Sweden)

    Umarphorn Chadseesuwan

    2016-10-01

    Full Text Available Aflatoxin M1 (AFM1 is a toxic metabolite of the fungal product aflatoxin found in milk. For food safety concern, maximum residual limits of AFM1 in milk and dairy products have been differently enforced in many countries. A suitable detection method is required to screen a large number of product samples for the AFM1 contamination. In this study, monoclonal antibodies (MAbs against AFM1 were generated using a conventional somatic cell fusion technique. After screening, five MAbs (AFM1-1, AFM1-3, AFM1-9, AFM1-11, and AFM1-17 were obtained that showed cross-reactivity with aflatoxin B1 (AFB1 and aflatoxin G1 (AFG1 but with no other tested compounds. An indirect competitive enzyme-linked immunosorbent assay (ELISA using a partially purified MAb and antigen-coated plates yielded the best sensitivity with the 50% inhibition concentration (IC50 and the limit of detection (LOD values of 0.13 ng/mL and 0.04 ng/mL, respectively. This indirect competitive ELISA was used to quantify the amount of fortified AFM1 in raw milk. The precision and accuracy in terms of % coefficient of variation (CV and % recovery of the detection was investigated for both intra- (n = 6 and inter- (n = 12 variation assays. The % CV was found in the range of 3.50–15.8% and 1.32–7.98%, respectively, while the % recovery was in the range of 92–104% and 100–103%, respectively. In addition, the indirect ELISA was also used to detect AFM1 fortified in processed milk samples. The % CV and % recovery values were in the ranges of 0.1–33.0% and 91–109%, respectively. Comparison analysis between the indirect ELISA and high performance liquid chromatography was also performed and showed a good correlation with the R2 of 0.992 for the concentration of 0.2–5.0 ng/mL. These results indicated that the developed MAb and ELISA could be used for detection of AFM1 in milk samples.

  15. Determination of Genotypic Performances of White Clover (Trifolium repens L. Collected from Natural Pastures

    Directory of Open Access Journals (Sweden)

    Celalettin Aygün

    2014-04-01

    Full Text Available This study was conducted to fine out morphological and physiological characteristics of white clover genotypes obtained from different location of Eastern Anatolia pastures. Similarities/dissimilarities in white clover genotypes and plant characteristics’ by principle components analysis were made. Plant height as a depended variable the affect of criteria on plant height and critic the best model to calcify genotype were made in white clover. As a result, wide variations were determined in not only plant characteristics but also genotypes. This was variation in other word genetic differentiations. Genetic differentiation on genotypes in white clover could help plant selection in white clover breeding present. Study showed that white clover breeding may be based on erect and prostrate plant selection. Plant characteristics and genotypes were classified in five certain groups on plant height.

  16. Chlorophyll a fluorescence to phenotype wheat genotypes for heat tolerance

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari; Andersen, Sven Bode; Ottosen, Carl-Otto

    . Chlorophyll a fluorescence has been a versatile tool in photosynthesis research to measure plant responses to various abiotic stresses that affect PSII. We aim to establish a reproducible protocol to measure response of wheat genotypes to high temperature, based on the physiological marker, maximum quantum......%. Our protocol seems to be stable over environments since interaction between genotypes and the three repeated experiments separated in time was not statistically significant. The chlorophyll a fluorescence protocol may enable identification of wheat lines reliably more or less tolerant to heat stress...

  17. Ethics control of vertebrate animals experiments in biosatellite BION-M1 project

    Science.gov (United States)

    Ilyin, Eugene

    During April 19-May 19, 2013 it was realized 30-days flight of Russian biosatellite Bion-M1. The main goal of this flight was to study effects of microgravity upon behavior and structural-functional state of different physiological systems of vertebrates. The folloving species were accommodated aboard of biosatellite: 45 mice C57bl/6, 8 Mongolian gerbils Meriones unguiculatus, 15 lizards, i.e. geckos Chondrodctylus turneri Gray, and fish Oreochromis mossambicus. The selection and traing of mice for the flight and ground-based control experiments was carried out at the Research Institute of Mitoengineering by Moscow State University. The protocols for animals care and reserch were revised and adopted by Bioethics Commission of above mentioned institute (decision on November 01, 2013, N35). The final version of Bion-M1 Scientific Reseach Program and protocols for separate experiments were discussed and adopted by Biomedical Ethics Commission of Institute of Biomedical Problems (decision on April 4, 2014, N317). The IMBP Commission has a status of Physiological Section of Russian Bioethics Committee by Russian Commision for UNESCO affairs and follows the Russian Bioethical Guidelines for Experiments in Aerospace and Naval Medicine and other national and international rules including COSPAR International Policy and Guidelines for Animal Care and Use in Space-born Research. Because US-scientists were the main partners in mice investigations the decision of IMBP Biomedical Commission related to Bion-M1 project was sended for information to Institutional Animal Care and Use Committee of NASA Ames Research Center. Postflight estimation of mice was done by Russian veterinary with the participation of NASA Chief veterinary.

  18. Spatio-kinematics of the optical nebula M1-92 with HST/STIS

    Science.gov (United States)

    Ramos-Medina, J.; Sánchez-Contreras, C.; Sahai, R.; Bujarrabal, V.; Castro-Carrizo, A.; Morris, M.

    2014-04-01

    We report optical long-slit spectroscopy with HST/STIS of the well known pre-Planetary Nebula (pPN) M1-92 (a.k.a. Minkowski's footprint). Complementary long-slit echelle spectra obtained with Keck II+ESI have been also used. We have used our high-angular (~0.1arcsec) resolution spectra to characterize the spatio-kinematic structure of the optical nebula of this object. From the analysis of the Halpha two-dimensional profile we identify several distinct nebular components at different spatial scales. The blue-shifted absorption component of the broad 'P cygni'-like profile of the Halpha emission is spatially and spectrally resolved and is found to be composed of not one but two different features centered at Vlsr~-600 and -200 km/s. To assist in the interpretation of the data, we have used a simple spatio-kinematic model which has allowed us to describe the main properties of the fast, bipolar winds (expanding with velocities of up to ~700 km/s) running inside the reflection lobes of M1-92 and that produce the absorptions. At the nebula center, we also discover an equatorially extended H-alpha emitting region that is expanding at moderate velocity (~300 km/s) in the direction perpendicular to the lobes. We have estimated the column density of the inner post-AGB winds and other physical parameters that have helped improving our understanding of the evolutionary history of M1-92.

  19. Relationship between pattern of ischemic manifestation and hemodynamics in symptomatic M1 stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Tokumitsu, Naoki; Sako, Kazuhiro; Aizawa, Shizuka; Shirai, Wakako [Nayoro City Hospital, Hokkaido (Japan)

    2002-07-01

    The mechanism through which ischemic manifestations develop in patients with middle cerebral artery (MCA) stenosis is still uncertain. It may cause ischemic symptoms through both embolic and hemodynamic mechanisms. In this study, we compared the findings from cerebral angiograms with single photon emission computed tomography (SPECT) in patients with M1 stenosis to determine the pathogenesis of ischema. At our hospital from 1994 to 2000, 14 patients (12 males and 2 females; mean age, 60.9; range, 31 to 85 years) with angiographically demonstrated symptomatic M1 stenosis were enrolled in this study. In 10, their stenotic lesion was located at the proximal site of the perforating arteries and for the other 4, stenosis was found at the distal site. Nine presented with transient ischemic attack (TIA) and 5 with completed stroke for an initial episode. The discrepancy in regional cerebral blood flow (rCBF) was evaluated in relation to the site and degree of stenosis, type of ischemic presentation, and frequency of ischemic events. There was no significant difference in CBF between the patients with stenosis involving the proximal site and those with distal stenosis; but the cortical CBF decreased significantly in those with severe stenosis compared with moderate stenosis. The cortical CBF of those who had a complete stroke is similar to that of the patients with TIA; but CBF of BGA decreased significantly in those with a complete stroke. The single ischemic event group showed a significant decrease in cortical CBF. On the other hand, the group with multiple ischemic events exhibited normal hemodynamics. We concluded that multiple ischemic events that occurred in M1 stenosis are caused by an embolic mechanism. (author)

  20. ISSR Analysis of M_1 Generation of Gladiolus hybridus Hort Treated by EMS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Gladiolus hybridus Hort is one of famous cutting flowers,being famous of big size,bright color,various shapes and long bloom period.New species should be cultivated in order to meet consumers' needs.Mutagenic breeding is a shortcut to cultivate new species of flowers.In this study,corm bud of G.hybridus Hort was treated with different concentrations of EMS.Then M 1 generation was analyzed by ISSR.Results showed that EMS was a very effective mutagenic agent for the corm bud of G.hybridus Hort.With the increa...

  1. Aflatoxin M1 level in pasteurized and sterilized milk of Babol city

    Directory of Open Access Journals (Sweden)

    Hashemi S J

    2007-11-01

    Full Text Available Background: Aflatoxins are severe toxic secondary metabolites found in most plant products. When animals consume contaminated feed stuff to Aflatoxin B1 (AFB1, the toxin is metabolized by liver and is excreted as Aflatoxin M1 (AFM1 via milk. Aflatoxins are acute toxic compounds, immunosuppressive, mutagen, tratogen and carcinogen."nMethods: During the winter of 2006, pasteurized and sterilized (ultra high temperature (UHT milk packages were collected from supermarkets in Babol city. 78 pasteurized and 33 sterilized milk, totally 111 samples were tested for AFM1 by competitive Enzyme Linked Immunosorbent Assay (ELISA. Solid phase in plastic micro wells coated whit anti-Aflatoxin M1 antibodies. We added 100 microliter skimmed milk and Aflatoxin M1 standard solutions in each well. In each plate, we appointed seven wells for standards. Plates were incubated at 20-25 centigrade for 45 min. Each well was washed four times by washing buffer 20X concentration. Then 100 micro liter conjugated solution (100X was added to each well, and the plate was incubated at 20-25 centigrade for 15 min. After that, the wells were washed. After adding the substrates to wells, we incubated the plate at 20-25 centigrade in a dark place for 15 min. The reaction was stopped by stop solution. After one hour, light absorption was read at 450 nm by ELISA reader."nResults: AFM1 were detected in 100% of all samples. 100% of samples were above of European community regulations (50ng/l. AFM1 contamination mean levels pasteurized and sterilized milk were 230.5 and 221.66 respectively. Therefore more than four fold levels European community. There is not a significant relationship between AFM1 contamina-tion level and different months of winter applying statistical test."nConclusion: The results showed the need for introducing safety limits for AFM1 levels in child milk under Food Legislative liable of Iran. Aflatoxin M1 contamination is a serious problem for public health

  2. Daniel Hertz SA M1落地式音箱

    Institute of Scientific and Technical Information of China (English)

    许成文

    2011-01-01

    Daniel Hertz SA M1落地式音箱在箱体结构上取经典造型。毫无疑问,Daniel Hertz的SAM1落地式音箱甫一亮相干市场,便已经奠定了它作为一代经典作品的基础——这不仅使其采用最经典的前障板布局和单元配置,在更大的程度上还包括它的综合技术内涵。

  3. THE DETECTION OF C60 IN THE WELL-CHARACTERIZED PLANETARY NEBULA M1-11

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Masaaki; Kemper, F. [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 10617, Taiwan (China); Hyung, S. [School of Science Education (Astronomy), Chungbuk National University, CheongJu, Chungbuk 361-763 (Korea, Republic of); Sargent, B. A.; Meixner, M. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Tajitsu, A. [Subaru Telescope, NAOJ, 650 North A' ohoku Place, Hilo, HI 96720 (United States); Yanagisawa, K., E-mail: otsuka@asiaa.sinica.edu.tw [Okayama Astrophysical Observatory (OAO), NAOJ, Kamogata, Okayama 719-0232 (Japan)

    2013-02-10

    We performed multiwavelength observations of the young planetary nebula (PN) M1-11 and obtained its elemental abundances, dust mass, and the evolutionary status of the central star. The AKARI/IRC, VLT/VISIR, and Spitzer/IRS spectra show features due to carbon-rich dust, such as the 3.3, 8.6, and 11.3 {mu}m features due to polycyclic aromatic hydrocarbons (PAHs), a smooth continuum attributable to amorphous carbon, and the broad 11.5 and 30 {mu}m features often ascribed to SiC and MgS, respectively. We also report the presence of an unidentified broad feature at 16-22 {mu}m, similar to the feature found in Magellanic Cloud PNe with either C-rich or O-rich gas-phase compositions. We identify for the first time in M1-11 spectral lines at 8.5 (blended with PAH), 17.3, and 18.9 {mu}m that we attribute to the C{sub 60} fullerene. This identification is strengthened by the fact that other Galactic PNe in which fullerenes are detected have similar central stars, similar gas-phase abundances, and a similar dust composition to M1-11. The weak radiation field due to the relatively cool central stars in these PNe may provide favorable conditions for fullerenes to survive in the circumstellar medium. Using the photoionization code CLOUDY, combined with a modified blackbody, we have fitted the {approx}0.1-90 {mu}m spectral energy distribution (SED) and determined the dust mass in the nebula to be {approx}3.5 Multiplication-Sign 10{sup -4} M {sub Sun }. Our chemical abundance analysis and SED model suggest that M1-11 is perhaps a C-rich PN with C/O ratio in the gas phase of +0.19 dex, and that it evolved from a 1-1.5 M {sub Sun} star.

  4. Scaled-energy spectroscopy of helium \\|M\\|=1 Rydberg atoms in a static electric field

    Science.gov (United States)

    Kips, Annemieke; Vassen, Wim; Hogervorst, Wim; Dando, Paul A.

    1998-10-01

    We present scaled-energy spectra on helium Rydberg atoms in a static electric field. \\|M\\|=1 states were studied in excitation from the 2 1S0 metastable state. Spectra were recorded for ɛ=-2.940(4), ɛ=-2.350(4), both below the saddle point, and ɛ=-1.760(4), above the saddle point. Closed-orbit theory was applied to interpret the spectra. A recent extension to closed-orbit theory, incorporating core effects, was used. This significantly improved agreement between experiment and theory.

  5. Enhancement of M1 Transition Rates at High Spin in 90Mo

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-Guang; YANG Chun-Xiang; LI Guang-Sheng; PENG Zhao-Hua; WEN Shu-Xian; HAN Guang-Bing; LI Cheng-Po; LU Shao-Jun; WU Shao-Yong; YUAN Guan-Jun

    2001-01-01

    High spin states in 90Mo have been populated through the 59Co (35C1,2p2n) 90Mo reaction at a beam energy of116 Me V. Level lifetimes of the positive-parity decay sequence are measured by using the Doppler shift attenuationmethod. It is observed that the M1 transition strengths show a substantial enhancement at high spin. Thisbehaviour may be related to occupation of high Ω orbitals by a pair of g9/2 protons. A deformed, oblate, shapeis suggested above the 13+ state.

  6. Asymmetric Mach-Zehnder Interferometer Based Biosensors for Aflatoxin M1 Detection.

    Science.gov (United States)

    Chalyan, Tatevik; Guider, Romain; Pasquardini, Laura; Zanetti, Manuela; Falke, Floris; Schreuder, Erik; Heideman, Rene G; Pederzolli, Cecilia; Pavesi, Lorenzo

    2016-01-06

    In this work, we present a study of Aflatoxin M1 detection by photonic biosensors based on Si₃N₄ Asymmetric Mach-Zehnder Interferometer (aMZI) functionalized with antibodies fragments (Fab'). We measured a best volumetric sensitivity of 10⁴ rad/RIU, leading to a Limit of Detection below 5 × 10(-7) RIU. On sensors functionalized with Fab', we performed specific and non-specific sensing measurements at various toxin concentrations. Reproducibility of the measurements and re-usability of the sensor were also investigated.

  7. AN M/M/1/N FEEDBACK QUEUING SYSTEM WITH REVERSE BALKING

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2015-06-01

    Full Text Available In this paper we develop an M/M/1/N feedback queuing system with reverse balking. Reverse balking is a type of customer behavior according to which an arriving customer joins a system with high probability if he encounters large system size and vice-versa. This behavior of a customer can be observed in many businesses such as investment. Feedback customer in queuing literature refers to a customer who is unsatisfied with incomplete, partial or unsatisfactory service. We derive the steady-state solution of the model and obtain some important measures of performance. Sensitivity analysis of the model is also performed with respect to the parameters involved.

  8. E1M1 and E1E2 transition probabilities in one-electron ions

    Science.gov (United States)

    Labzowsky, L. N.; Shonin, A. V.

    2004-12-01

    The quantum electrodynamical (QED) theory of the two-photon transitions in hydrogenlike ions is presented. The emission probability for 2s→2γ(E1)+1s transitions is calculated and compared to the results of the previous calculations. The emission probabilities 2p→γ(E1)+γ(E2)+1s and 2p→γ(E1)+γ(M1)+1s are also calculated for the nuclear charge Z values 1⩽Z⩽100. This is the first calculation of the two latter probabilities. The results are given in two different gauges.

  9. STS-34 crewmembers sit in M1-13 APC during emergency egress training at KSC

    Science.gov (United States)

    1989-01-01

    STS-34 crewmembers sit in M1-13 Armored Personnel Carrier (APC) during emergency egress training at KSC's shuttle landing facility (SLF) prior to terminal countdown demonstration test (TCDT) activities. Wearing launch and entry suits (LESs), are (from left) Mission Specialist (MS) Ellen S. Baker, MS Shannon W. Lucid, Commander Donald E. Williams (right side, in back), MS Franklin R. Chang-Diaz, and Pilot Michael J. McCulley (holding headset). View provided by KSC with alternate number KSC-89PC-871.

  10. The M/M/1 queue with inventory, lost sale and general lead times

    DEFF Research Database (Denmark)

    Saffari, Mohammad; Asmussen, Søren; Haji, Rasoul

    We consider an M/M/1 queueing system with inventory under the (r,Q) policy and with lost sales, in which demands occur according to a Poisson process and service times are exponentially distributed. All arriving customers during stockout are lost. We derive the stationary distributions of the joi...... queue length (number of customers in the system) and on-hand inventory when lead times are random variables and can take various distributions. The derived stationary distributions are used to formulate long-run average performance measures and cost functions in some numerical examples....

  11. Population samples and genotyping technology.

    Science.gov (United States)

    Mack, S J; Sanchez-Mazas, A; Single, R M; Meyer, D; Hill, J; Dron, H A; Jani, A J; Thomson, G; Erlich, H A

    2007-04-01

    The 14th International HLA (human leukocyte antigen) Immunogenetics Workshop (14th-IHIWS) Biostatistics and Anthropology/Human Genetic Diversity project continues the population sampling, genotype data generation, and biostatistic analyses of the 13th International Histocompatibility Workshop Anthropology/Human Genetic Diversity Component, with the overall goal of further characterizing global HLA allele and haplotype diversity and better describing the relationships between major histocompatibility complex diversity, geography, linguistics, and population history. Since the 13th Workshop, new investigators have and continue to be recruited to the project and new high-resolution class I and class II genotype data are being generated for 112 population samples from around the world.

  12. Elevated carbon dioxide alters the relative fitness of Taraxacum officinale genotypes

    Science.gov (United States)

    I tested whether elevated carbon dioxide concentration differentially affected which genotypes of the apomictic species dandelion produced the largest number of viable seeds in two different field experiments, and identified morphological and physiological traits associated with fitness at elevated ...

  13. Pooled DNA genotyping on Affymetrix SNP genotyping arrays

    Directory of Open Access Journals (Sweden)

    Owen Michael J

    2006-02-01

    Full Text Available Abstract Background Genotyping technology has advanced such that genome-wide association studies of complex diseases based upon dense marker maps are now technically feasible. However, the cost of such projects remains high. Pooled DNA genotyping offers the possibility of applying the same technologies at a fraction of the cost, and there is some evidence that certain ultra-high throughput platforms also perform with an acceptable accuracy. However, thus far, this conclusion is based upon published data concerning only a small number of SNPs. Results In the current study we prepared DNA pools from the parents and from the offspring of 30 parent-child trios that have been extensively genotyped by the HapMap project. We analysed the two pools with Affymetrix 10 K Xba 142 2.0 Arrays. The availability of the HapMap data allowed us to validate the performance of 6843 SNPs for which we had both complete individual and pooled genotyping data. Pooled analyses averaged over 5–6 microarrays resulted in highly reproducible results. Moreover, the accuracy of estimating differences in allele frequency between pools using this ultra-high throughput system was comparable with previous reports of pooling based upon lower throughput platforms, with an average error for the predicted allelic frequencies differences between the two pools of 1.37% and with 95% of SNPs showing an error of Conclusion Genotyping thousands of SNPs with DNA pooling using Affymetrix microarrays produces highly accurate results and can be used for genome-wide association studies.

  14. M1-46: A Case Study on Multiple-Shell Planetary Nebula Formation

    Science.gov (United States)

    Guerrero, M. A.; Manchado, A.; Stanghellini, L.; Herrero, A.

    1996-06-01

    We discuss in detail the evolutionary path of the multiple-shell planetary nebula M1-46, in the light of our new observations. The velocities of the halo and main nebula correspond to a dynamical time lap between the shells of about 6.8 x 104 yr. By means of a non-LTE analysis of the central star's spectrum, we derived a stellar temperature of Teff = 45,000 K, which, coupled to the visual magnitude and an appropriate bolometric correction, gives a stellar luminosity of 5370 Lsun. The mass of the central star has been evaluated to be 0.6 Msun, and its interpulse time on the asymptotic giant branch is 7.6 x 104 yr. The agreement between the observed intershell time lap and the evolutionary interpulse time lap points to the fact that the formation of this planetary nebula could be ascribed to the gasping mass loss associated with the thermal pulses at the thermally pulsating asymptotic giant branch. The high-resolution spatially resolved observations reveal the presence of different kinematical components in the main nebula which cannot be understood in a homogeneous expanding shell scenario. As regards the chemical abundances, M1-46 has the typical abundances of a type II planetary nebula. No definite abundance gradient between the shells is found.

  15. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J.; Lowther, Jonathan; Stack, Colin M.; Golding, Sarah J.; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Teuscher, Franka; Donnelly, Sheila M.; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; DeGori, Ross; Buckle, Ashley M.; Gardiner, Donald L.; Whisstock, James C.; Dalton, John P.

    2009-01-01

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH2]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite. PMID:19196988

  16. 新加坡M1与Vodafone达成漫游协议

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    为了让经常旅游的客户能够更方便有效地使用数据业务。新加坡M1用户推出了数据漫游业务。用户在Vodafone的网络上进行数据漫游时,将只需支付本地数据资费,从而节省了60%的数据使用费。这一优惠目前可以在8个有Vodafone网络运营的国家实现,今年早些时候将有超过30个国家可以享受到这项服务,包括一些很流行的漫游目的地,如香港、法国、英国、澳大利亚和德国。随着数据漫游资费的推出,M1成为新加坡第一个提供在Vodafone网络上的单一数据漫游资费的移动运营商。

  17. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase.

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J; Lowther, Jonathan; Stack, Colin M; Golding, Sarah J; Skinner-Adams, Tina S; Trenholme, Katharine R; Teuscher, Franka; Donnelly, Sheila M; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; Degori, Ross; Buckle, Ashley M; Gardiner, Donald L; Whisstock, James C; Dalton, John P

    2009-02-24

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH(2)]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite.

  18. Determination of aflatoxin M1 levels in Iranian white and cream cheese.

    Science.gov (United States)

    Fallah, Aziz A; Jafari, Tina; Fallah, Ali; Rahnama, Mohammad

    2009-08-01

    A screening survey on the occurrence of aflatoxin M1 (AFM1) was accomplished on 210 cheese samples composed of white cheese (116 samples) and cream cheese (94 samples) purchased from popular markets in central part of Iran (Esfahan and Yazd provinces). The quantitative analysis of AFM1 levels in the samples was performed by using the competitive enzyme-linked immunosorbent assay (ELISA) technique. Aflatoxin M1 at measurable level (50 ng/kg) was detected in 161 (76.6%) samples, consisting of 93 (80.1%) white and 68 (72.3%) cream cheese samples. The concentration of AFM1 in the samples ranged from 52.1 to 785.4 ng/kg. Comparing to legal regulation (250 ng/kg) accepted by some of the countries, 24.2% of the samples exceeded the accepted limit. Among these, the AFM1 levels in 28.4% of white and 19.1% of cream cheese samples were not in accordance with the safety limit. The results indicated that contamination of the samples with AFM1 in such a level appear to be a potential hazard for public health. This paper represents the data of the first survey on the occurrence of AFM1 in cheeses consumed in central part of Iran.

  19. Pirenzepine Promotes the Dimerization of Muscarinic M1 Receptors through a Three-step Binding Process*

    Science.gov (United States)

    Ilien, Brigitte; Glasser, Nicole; Clamme, Jean-Pierre; Didier, Pascal; Piemont, Etienne; Chinnappan, Raja; Daval, Sandrine B.; Galzi, Jean-Luc; Mely, Yves

    2009-01-01

    Ligand binding to G protein-coupled receptors is a complex process that involves sequential receptor conformational changes, ligand translocation, and possibly ligand-induced receptor oligomerization. Binding events at muscarinic acetylcholine receptors are usually interpreted from radioligand binding studies in terms of two-step ligand-induced receptor isomerization. We report here, using a combination of fluorescence approaches, on the molecular mechanisms for Bodipy-pirenzepine binding to enhanced green fluorescent protein (EGFP)-fused muscarinic M1 receptors in living cells. Real time monitoring, under steady-state conditions, of the strong fluorescence energy transfer signal elicited by this interaction permitted a fine kinetic description of the binding process. Time-resolved fluorescence measurements allowed us to identify discrete EGFP lifetime species and to follow their redistribution upon ligand binding. Fluorescence correlation spectroscopy, with EGFP brightness analysis, showed that EGFP-fused muscarinic M1 receptors predominate as monomers in the absence of ligand and dimerize upon pirenzepine binding. Finally, all these experimental data could be quantitatively reconciled into a three-step mechanism, with four identified receptor conformational states. Fast ligand binding to a peripheral receptor site initiates a sequence of conformational changes that allows the ligand to access to inner regions of the protein and drives ligand-receptor complexes toward a high affinity dimeric state. PMID:19451648

  20. Fluorescent pirenzepine derivatives as potential bitopic ligands of the human M1 muscarinic receptor.

    Science.gov (United States)

    Tahtaoui, Chouaib; Parrot, Isabelle; Klotz, Philippe; Guillier, Fabrice; Galzi, Jean-Luc; Hibert, Marcel; Ilien, Brigitte

    2004-08-12

    Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, we synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All molecules reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant. This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other molecules (15-24 atom long linkers) is not. The data favor the idea that these analogues might interact with both the acetylcholine and the brucine binding domains. Copyright 2004 American Chemical Society

  1. Pirenzepine promotes the dimerization of muscarinic M1 receptors through a three-step binding process.

    Science.gov (United States)

    Ilien, Brigitte; Glasser, Nicole; Clamme, Jean-Pierre; Didier, Pascal; Piemont, Etienne; Chinnappan, Raja; Daval, Sandrine B; Galzi, Jean-Luc; Mely, Yves

    2009-07-17

    Ligand binding to G protein-coupled receptors is a complex process that involves sequential receptor conformational changes, ligand translocation, and possibly ligand-induced receptor oligomerization. Binding events at muscarinic acetylcholine receptors are usually interpreted from radioligand binding studies in terms of two-step ligand-induced receptor isomerization. We report here, using a combination of fluorescence approaches, on the molecular mechanisms for Bodipy-pirenzepine binding to enhanced green fluorescent protein (EGFP)-fused muscarinic M1 receptors in living cells. Real time monitoring, under steady-state conditions, of the strong fluorescence energy transfer signal elicited by this interaction permitted a fine kinetic description of the binding process. Time-resolved fluorescence measurements allowed us to identify discrete EGFP lifetime species and to follow their redistribution upon ligand binding. Fluorescence correlation spectroscopy, with EGFP brightness analysis, showed that EGFP-fused muscarinic M1 receptors predominate as monomers in the absence of ligand and dimerize upon pirenzepine binding. Finally, all these experimental data could be quantitatively reconciled into a three-step mechanism, with four identified receptor conformational states. Fast ligand binding to a peripheral receptor site initiates a sequence of conformational changes that allows the ligand to access to inner regions of the protein and drives ligand-receptor complexes toward a high affinity dimeric state.

  2. Molecular Probes for Muscarinic Receptors: Derivatives of the M1-Antagonist Telenzepine

    Science.gov (United States)

    Karton, Yishai; Baumgold, Jesse; Handen, Jeffrey S.; Jacobson, Kenneth A.

    2012-01-01

    Functionalized congeners of the M1-selective muscarinic antagonist telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H-thieno[3,4–b][1,5]benzodiazepin-10-one) were developed and found to bind to the receptor with affinities (Ki values) in approximately the nanomolar range. The derivatives contain a 10-aminodecyl group, which provides a nucleophilic functionality for further derivatization. The attachment of a spacer chain to the distal piperazinyl nitrogen was based on previous findings of enhanced affinity at muscarinic receptors in an analogous series of alkylamino derivatives of pirenzepine [J. Med. Chem. (1991) 34, 2133–2145]. The telenzepine derivatives contain prosthetic groups for radioiodination, protein cross-linking, photoaffinity labeling, and fluorescent labeling and biotin for avidin complexation. The affinity for muscarinic receptors in rat forebrain (mainly m1 subtype) was determined in competitive binding assays vs [3H]-N-methylscopolamine. A (p-aminophenyl)-acetyl derivative for photoaffinity labeling had a Ki value of 0.29 nM at forebrain muscarinic receptors (16-fold higher affinity than telenzepine). A biotin conjugate displayed a Ki value of 0.60 nM at m2-receptors and a 5-fold selectivity versus forebrain. The high affinity of these derivatives makes them suitable for the characterization of muscarinic receptors in pharmacological and spectroscopic studies, for peptide mapping, and for histochemical studies. PMID:1520727

  3. Process economics and safety considerations for the oxidative dehydrogenation of ethane using the M1 catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Baroi, Chinmoy; Gaffney, Anne M.; Fushimi, Rebecca

    2017-05-01

    Olefins or unsaturated hydrocarbons play a vital role as feedstock for many industrially significant processes. Ethylene is the simplest olefin and a key raw material for consumer products. Oxidative Dehydrogenation (ODH) is one of the most promising new routes for ethylene production that can offer a significant advantage in energy efficiency over the conventional steam pyrolysis process. This study is focused on the ODH chemistry using the mixed metal oxide MoVTeNbOx catalysts, generally referred to as M1 for the key phase known to be active for dehydrogenation. Using performance results from the patent literature a series of process simulations were conducted to evaluate the effect of feed composition on operating costs, profitability and process safety. The key results of this study indicate that the ODH reaction can be made safer and more profitable without use of an inert diluent and furthermore by replacing O2 with CO2 as an oxidant. Modifications of the M1 catalyst composition in order to adopt these changes are discussed.

  4. Microscopic description of low-lying M1 excitations in odd-mass actinide nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Tabar, Emre, E-mail: etabar@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Yakut, Hakan, E-mail: hyakut@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Kuliev, Ali Akbar [Azerbaijan National Academy of Aviation, Baku (Azerbaijan)

    2017-01-15

    A restoration method of a broken symmetry which allows self-consistent determination of the separable effective restoration forces is now adapted to odd-mass nuclei in order to restore violated rotational invariance (RI-) of the Quasiparticle Phonon Nuclear Model (QPNM) Hamiltonian. Because of the self-consistency of the method, these effective forces contain no arbitrary parameters. Within RI-QPNM, the properties of the low-lying magnetic dipole excitations in odd-mass deformed {sup 229–233}Th and {sup 233–239}U nuclei have been investigated for the first time. It has been shown that computed fragmentation of the M1 strengths below 4 MeV in these nuclei is much stronger than that in neighboring doubly even {sup 228–232}Th and {sup 232–238}U nuclei. For {sup 235}U the summed M1 strength in the energy range 1.5–2.8 MeV is in agreement with the relevant experimental data where the missing strength was extracted by means of a fluctuation analysis.

  5. Quadrupole decay strength of the M1 scissors mode of {sup 156}Gd

    Energy Technology Data Exchange (ETDEWEB)

    Beck, T.; Beller, J.; Gayer, U.; Mertes, L.; Pai, H.; Pietralla, N.; Ries, P.; Romig, C.; Werner, V.; Zweidinger, M. [IKP, TU Darmstadt (Germany); Derya, V. [IKP, Universitaet zu Koeln (Germany); Isaak, J.; Loeher, B.; Savran, D. [EMMI, GSI, Darmstadt (Germany); FIAS, Frankfurt (Germany); Scheck, M. [IKP, TU Darmstadt (Germany); School of Engineering, UWS, Paisley (United Kingdom); SUPA, Glasgow (United Kingdom); Tornow, W.; Weller, H.R. [Duke University, Durham (United States)

    2015-07-01

    The isovector low-lying J{sup π}{sub K}=1{sup +}{sub 1} scissors mode of deformed nuclei has been studied extensively in (e,e{sup '}) and (γ,γ{sup '}) experiments over the last 30 years with the main focus on strong M1 transitions to the ground state band. In the framework of the semiclassical two-rotor-model it has its origin in quadrupole deformation. A considerable E2 matrix element between the rotational band of the scissors mode and the ground band is predicted which has not been addressed experimentally. A photon-scattering experiment with linearly-polarized quasi monoenergetic vector (γ)-rays has been performed at the High Intensity vector (γ)-ray Source (HIvector (γ)S) at Duke University, Durham, NC, exploiting the γ{sup 3} setup. We have measured an E2/M1-multipole mixing ratio for the 1{sup +}{sub sc}→2{sup +}{sub 1} transition for the first time. The Alaga rule is applicable and delivers a first estimate of the transition strength B(E2:2{sup +}{sub sc}→0{sup +}{sub 1}). A candidate for a 2{sup +}{sub sc}→2{sup +}{sub 1} transition is discussed.

  6. The Truth-Telling Motor Cortex: Response Competition in M1 Discloses Deceptive Behaviour

    Directory of Open Access Journals (Sweden)

    Aviad A. Hadar

    2011-05-01

    Full Text Available Recent studies have suggested that circuits associated with response conflict and response inhibition are strongly implicated in deception. Using single-pulse transcranial magnetic stimulation (TMS, we examined whether conflict between competing responses in primary motor cortex (M1 can be used for discriminating between intentionally false and true facial recognition. Participants used little finger and thumb key-presses to lie or tell the truth regarding their familiarity with a series of famous and nonfamous faces. Single-pulse TMS was administered to M1 at three intervals prior to response execution in order to evoke motor evoked potentials (MEPs in both Abductor Digiti Minimi (ADM and first dorsal interosseous (FDI of the right hand. As predicted, we found that the MEP of the nonresponding digit was greater than the MEP of the responding digit when participants prepared to engage in deception, while a mirror-reversed pattern was observed for truth telling. This effect did not interact with the stimulation interval suggesting consistent activation of the motor plan representing the truth throughout the response preparation process. We discuss these results with reference to models of response selection and procedures for the detection of deception.

  7. Microscopic description of low-lying M1 excitations in odd-mass actinide nuclei

    Science.gov (United States)

    Tabar, Emre; Yakut, Hakan; Kuliev, Ali Akbar

    2017-01-01

    A restoration method of a broken symmetry which allows self-consistent determination of the separable effective restoration forces is now adapted to odd-mass nuclei in order to restore violated rotational invariance (RI-) of the Quasiparticle Phonon Nuclear Model (QPNM) Hamiltonian. Because of the self-consistency of the method, these effective forces contain no arbitrary parameters. Within RI-QPNM, the properties of the low-lying magnetic dipole excitations in odd-mass deformed 229-233Th and 233-239U nuclei have been investigated for the first time. It has been shown that computed fragmentation of the M1 strengths below 4 MeV in these nuclei is much stronger than that in neighboring doubly even 228-232Th and 232-238U nuclei. For 235U the summed M1 strength in the energy range 1.5-2.8 MeV is in agreement with the relevant experimental data where the missing strength was extracted by means of a fluctuation analysis.

  8. Involvement of an Arginine Triplet in M1 Matrix Protein Interaction with Membranes and in M1 Recruitment into Virus-Like Particles of the Influenza A(H1N1)pdm09 Virus

    Science.gov (United States)

    Moncorgé, Olivier; Panthu, Baptiste; Prchal, Jan; Décimo, Didier; Ohlmann, Théophile; Lina, Bruno; Favard, Cyril; Decroly, Etienne; Ottmann, Michèle; Roingeard, Philippe; Muriaux, Delphine

    2016-01-01

    The influenza A(H1N1)pdm09 virus caused the first influenza pandemic of the 21st century. In this study, we wanted to decipher the role of conserved basic residues of the viral M1 matrix protein in virus assembly and release. M1 plays many roles in the influenza virus replication cycle. Specifically, it participates in viral particle assembly, can associate with the viral ribonucleoprotein complexes and can bind to the cell plasma membrane and/or the cytoplasmic tail of viral transmembrane proteins. M1 contains an N-terminal domain of 164 amino acids with two basic domains: the nuclear localization signal on helix 6 and an arginine triplet (R76/77/78) on helix 5. To investigate the role of these two M1 basic domains in influenza A(H1N1)pdm09 virus molecular assembly, we analyzed M1 attachment to membranes, virus-like particle (VLP) production and virus infectivity. In vitro, M1 binding to large unilamellar vesicles (LUVs), which contain negatively charged lipids, decreased significantly when the M1 R76/77/78 motif was mutated. In cells, M1 alone was mainly observed in the nucleus (47%) and in the cytosol (42%). Conversely, when co-expressed with the viral proteins NS1/NEP and M2, M1 was relocated to the cell membranes (55%), as shown by subcellular fractionation experiments. This minimal system allowed the production of M1 containing-VLPs. However, M1 with mutations in the arginine triplet accumulated in intracellular clusters and its incorporation in VLPs was strongly diminished. M2 over-expression was essential for M1 membrane localization and VLP production, whereas the viral trans-membrane proteins HA and NA seemed dispensable. These results suggest that the M1 arginine triplet participates in M1 interaction with membranes. This R76/77/78 motif is essential for M1 incorporation in virus particles and the importance of this motif was confirmed by reverse genetic demonstrating that its mutation is lethal for the virus. These results highlight the molecular

  9. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D

    2016-01-01

    OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURC...

  10. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D;

    2016-01-01

    OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURC...

  11. Microsatellite genotyping of carnation varieties

    NARCIS (Netherlands)

    Smulders, M.J.M.; Noordijk, Y.; Rus-Kortekaas, W.; Bredemeijer, G.M.M.; Vosman, B.

    2003-01-01

    A set of 11 sequence-tagged microsatellite markers for carnation (Dianthus caryophyllus) was developed using a DNA library enriched for microsatellites. Supplemented with three markers derived from sequence database entries, these were used to genotype carnation varieties using a semi-automated fluo

  12. Genotyping with TaqMAMA.

    Science.gov (United States)

    Li, Baohui; Kadura, Ibrahim; Fu, Dong-Jing; Watson, David E

    2004-02-01

    TaqMAMA combines the quantitative strengths of TaqMan with the allele-specific PCR of MAMA. In this article we develop TaqMAMA as a technique for screening human DNA samples for known genetic polymorphisms. In the first set of experiments, plasmids that model all types of genetic polymorphisms were used to understand the relationship between TaqMAMA primer/template mismatches and their strength of allelic discrimination. These data can be used to improve allelic discrimination of other primer extension genotyping methodologies through directed use of nucleotide mismatches. We used the data to derive a guide for TaqMAMA primer design and DNA strand selection for TaqMAMA genotyping assays. The guide was then used to develop assays for 11 known and novel human genetic polymorphisms. Genotypes were assigned quickly and accurately in all cases. TaqMAMA genotyping assays require minimal development time, have a high probability of success, produce reliable data that are straightforward to analyze, and are very cost-competitive.

  13. 谷胱甘肽S-转移酶M1及T1基因突变对抗结核药致肝损伤的影响%The effect of GST M1 and GST T1 gene mutations on anti-tuberculous drug induced hepatic injury

    Institute of Scientific and Technical Information of China (English)

    郭梅; 孙永红; 李世明; 王东; 刘茜; 张喜英; 刘潇潇; 冯福民

    2009-01-01

    Objective To study the relationship between the polymorphisms of GST M1 and GST T1 genes and anti-tuberculous drug induced hepatic injury(ADIH).Methods A 1∶1 matched case-control study was carried out.One hundred and six patients[age(49±19)years,73 men and 33 womenl fulfilling the criteria of ADIH during the 3 month follow-up after the initiation of anti-tuberculous therapy were included,while 106 cases[age(49±19)years,73 men and 33 women]without any hepatic injury served as the controls.The genotypes of GST M1 and GsT T1 genetic potymorphisms were detected by polymerase chain reaction(PCR)in patients who received anti-tuberculosis therapy.Using SPSS 11.5 for windows software,univariate and multivariate conditional logistic analyses were conducted for studying the relationship between the polymorphisms and ADIH.Results Univariate analysis demonstrated that the"null"genotype of GST M1 gene occurred in 50(47.2%)of the cases,more frequent than in the controls [25(23.6%)],with a crude OR(95%CI)2.786(1.513-5.130).No significant association was observed between ADIH and GsT T1 polymorphism.Among the risk factors analyzed,body mass index and alcohol drinking were significantly associated with ADIH.In the multivariate analysis,a significant association between ADIH and the"null"genotype of GST M1 existed,after adjusting for body mass index and drinking status,adjusted OR(95% CI)being 3.022(1.540-5.926).Again,no significant association was observed between GsT T1 polymorphism and ADIH.Conclusion This study demonstrated that patients carrying GST M1-"null"genotype may be susceptible to ADIH.%目的 探讨谷胱甘肽S-转移酶(GST)M1、T1基因多态性与抗结核药所致肝损伤(ADIH)的相关性.方法 2005年8月至2006年7月,采用1∶1配对病例对照研究设计,选择从接受抗结核化疗开始随访3个月期间出现肝损伤(病例组106例)及未见肝损伤(对照组106例)的结核病患者,病例组男73例,女33例,年龄15~88岁,平均(49±19

  14. The human Müller cell line MIO-M1 expresses opsins.

    Science.gov (United States)

    Hollborn, Margrit; Ulbricht, Elke; Rillich, Katja; Dukic-Stefanovic, Sladjana; Wurm, Antje; Wagner, Lysann; Reichenbach, Andreas; Wiedemann, Peter; Limb, Gloria Astrid; Bringmann, Andreas; Kohen, Leon

    2011-01-01

    To determine whether the human Müller cell line Moorfields/Institute of Ophthalmology-Müller 1 (MIO-M1) expresses opsins. The gene expression of opsins was determined by reverse-transcription PCR (RT-PCR). The presence of opsin proteins was determined by western blotting and immunocytochemistry. The light sensitivity of the cells was examined with imaging experiments using the calcium-sensitive dye Fluo-4. MIO-M1 cells express glial (glutamine synthase [GLUL], vimentin [VIM], glial fibrillary acidic protein [GFAP], cellular retinaldehyde-binding protein [RLBP1], glial high-affinity glutamate transporter [SLCA1], aquaporin-4 [AQP4], inwardly rectifying potassium channel Kir4.1 [Kir4.1]), neuronal (Thy-1 cell surface antigen [THY1], heavy neurofilament polypeptide [NEFH], microtubule-associated protein 2 [MAP2], neurogenic differentiation 1 [NEUROD1], neuronal nuclei [NEUN]), and neural progenitor markers (Nestin [NES], paired-type homeobox transcription factor [PAX6], neurogenic locus notch homolog 1 [NOTCH1]). The cells contain mRNA for the following opsins: blue opsin (OPN1SW), rhodopsin (OPN2), panopsin (OPN3), melanopsin (OPN4), neuropsin (OPN5), and peropsin (RRH), as well as for the transducins (guanine nucleotide binding protein [GNAZ], alpha transducing activity polypeptide 1 [GNAT1], alpha transducing activity polypeptide 2 [GNAT2]). The presence of blue opsin and melanopsin was confirmed with immunocytochemistry and western blotting. The immunoreactivity and mRNA of red-green opsin were found in some but not all cultures, while the immunoreactivity for rhodopsin was absent in all cultures investigated. Repetitive stimulation with 480 nm light evoked slow and fast transient calcium responses in the majority of cells investigated, while irradiation with 600 nm light was ineffective. The human Müller cell line MIO-M1 expresses opsins. This suggests immortalized Müller cells could be used as a cellular source to produce human opsins for their potential

  15. State-dependent and timing-dependent bidirectional associative plasticity in the human SMA-M1 network.

    Science.gov (United States)

    Arai, Noritoshi; Müller-Dahlhaus, Florian; Murakami, Takenobu; Bliem, Barbara; Lu, Ming-Kuei; Ugawa, Yoshikazu; Ziemann, Ulf

    2011-10-26

    The supplementary motor area (SMA-proper) plays a key role in the preparation and execution of voluntary movements. Anatomically, SMA-proper is densely reciprocally connected to primary motor cortex (M1), but neuronal coordination within the SMA-M1 network and its modification by external perturbation are not well understood. Here we modulated the SMA-M1 network using MR-navigated multicoil associative transcranial magnetic stimulation in healthy subjects. Changes in corticospinal excitability were assessed by recording motor evoked potential (MEP) amplitude bilaterally in a hand muscle. We found timing-dependent bidirectional Hebbian-like MEP changes during and for at least 30 min after paired associative SMA-M1 stimulation. MEP amplitude increased if SMA stimulation preceded M1 stimulation by 6 ms, but decreased if SMA stimulation lagged M1 stimulation by 15 ms. This associative plasticity in the SMA-M1 network was highly topographically specific because paired associative stimulation of pre-SMA and M1 did not result in any significant MEP change. Furthermore, associative plasticity in the SMA-M1 network was strongly state-dependent because it required priming by near-simultaneous M1 stimulation to occur. We conclude that timing-dependent bidirectional associative plasticity is demonstrated for the first time at the systems level of a human corticocortical neuronal network. The properties of this form of plasticity are fully compatible with spike-timing-dependent plasticity as defined at the cellular level. The necessity of priming may reflect the strong interhemispheric connectivity of the SMA-M1 network. Findings are relevant for better understanding reorganization and potentially therapeutic modification of neuronal coordination in the SMA-M1 network after cerebral lesions such as stroke.

  16. Response of avocado genotypes to improvement through {sup 60}Co gamma radiation; Respuesta de diversos genotipos de aguacate al mejoramiento por radiacion gamma de {sup 60}Co

    Energy Technology Data Exchange (ETDEWEB)

    Cruz, E. De la; Rubi A, M.; Garcia A, J.M. [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    Ten avocado genotypes were subjected to gamma radiation from 0 to 45 Gy in 1993. Vegetative and reproductive data were analysed in a factorial design. Genotypes differed significative on height and fruit number. Radiation affected significative fruit number but not tree height. ''Hass'' showed strongest interaction between genotype and doses, for fruit number. (Author)

  17. Irreducible Modular Representations of the Reflection Group G(m,1,n

    Directory of Open Access Journals (Sweden)

    José O. Araujo

    2015-01-01

    Full Text Available In an article published in 1980, Farahat and Peel realized the irreducible modular representations of the symmetric group. One year later, Al-Aamily, Morris, and Peel constructed the irreducible modular representations for a Weyl group of type Bn. In both cases, combinatorial methods were used. Almost twenty years later, using a geometric construction based on the ideas of Macdonald, first Aguado and Araujo and then Araujo, Bigeón, and Gamondi also realized the irreducible modular representations for the Weyl groups of types An and Bn. In this paper, we extend the geometric construction based on the ideas of Macdonald to realize the irreducible modular representations of the complex reflection group of type G(m,1,n.

  18. E2 and M1 Transition Probabilities in Odd Mass Hg Nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Berg, V.; Baecklin, A.; Fogelberg, B.; Malmskog, S.G.

    1969-10-15

    L- and M-subshell ratios have been measured for the 39.5 keV transition in {sup 193}Hg and the 37.1 and 16.2 keV transitions in {sup 195}Hg yielding 0.38 {+-} 0.12 , <0.02 and 0.08 {+-} 0.03 per cent E2, respectively. The half-lives of the 39.5 keV level in {sup 193}Hg and the 53.3 and 37.1 keV levels in {sup 195}Hg have been measured by the delayed coincidence method, yielding values of 0.63 {+-} 0.03, 0.72 {+-} 0.03 and <0.05 nsec respectively. A systematic compilation of reduced E2 and M1 transition probabilities in odd mass Pt, Hg and Pb nuclei is given and compared to theoretical predictions.

  19. Occurrence of aflatoxin M(1) in dairy products in southern Italy.

    Science.gov (United States)

    Montagna, Maria Teresa; Napoli, Christian; De Giglio, Osvalda; Iatta, Roberta; Barbuti, Giovanna

    2008-12-01

    A screening survey of the presence of aflatoxin M(1) (AFM(1)) was carried out on 265 samples of cheese made from cow, buffalo, goat, sheep, sheep-goat milk collected in the Apulia region (Southern Italy). Selected samples included unripened, medium and long-term ripened cheeses. AFM(1) was found in 16.6% of the analyzed samples. The highest positive incidence was for medium and long-term ripened cheeses, especially those made from sheep-goat milk, while buffalo cheeses tested consistently negative. Our results show that the level of contamination by AFM(1) in dairy products from Apulia Region are lower than in other Italian and European regions. Moreover, it is important to underline that a common European norm concerning the AFM(1) threshold limits for dairy products is still lacking.

  20. Excretion of Aflatoxin M1 in milk of goats fed diet contaminated by Aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Gianni Battacone

    2010-01-01

    Full Text Available An experiment was carried out to study the excretion of aflatoxin M1(AFM1 in milk of three goats fed a single dose (0.8mg/head of pure aflatoxin B1 (AFB1. The values of AFM1 concentration excreted in milk was highly variable among goats, even if the pattern of excretion over time was very similar among the three animals. AFM1 was first detected at the milking performed 1h after the AFB1 administration. The highest values of AFM1 concentration in milk were reached 3 and 6h after the AFB1 intake. The trend of clearance of AFM1 in milk over time was expressed by a decreasing exponential equation. AFM1 concentration was below the EU maximum allowed level (50 ng/L in milk collected 36 h after the AFB1 administration.

  1. Robinson-Schensted-Knuth Correspondence and Weak Polynomial Identities of M1,1(E)

    Institute of Scientific and Technical Information of China (English)

    Onofrio Mario Di Vincenzo; Roberto La Scala

    2005-01-01

    In this paper, it is proved that the ideal Iω of the weak polynomial identities of the superalgebra M1,1(E) is generated by the p roper polynomials [x1,x2, x3] and [x2,x1][xa,x1][x4, x1]. This is proved for any infinite field F of characteristic different a basis and the dimension of any multihomogeneous component of the quotient algebra B/(B ∩ Iw). We also compute the Hilbert series of this algebra. One of the main tools of this paper is a variant we found of the Robinson-Schensted-Knuth correspondence defined for single semistandard tableaux of double shape.

  2. RAPD Analysis of M1 Generation of Gladiolus hybridus Hort Treated by EMS

    Institute of Scientific and Technical Information of China (English)

    WANG Jingang; GUO Ying; CHE Daidi; LIU Shenkui; YANG Chuanpin

    2009-01-01

    Gladiolus hybridus Hort is one of the world's famous cutting flowers. It is very popular because of the big size, bright color, various shape, and long period of bloom. New species should be cultivated in order to meet the consumers' need of asking for the new. Among the technologies of cultivating new species of flowers, mutagenic breeding is a shortcut. This study treated corm bud of G. hybridus Hort with EMS of different consistency. Then M1 after treated was analyzed by RAPD. The result showed that EMS was a very effective mutagenic agent for the corm bud of G. hybridus Hort. With the increase of consistency, the mutagenic range increased first, then decreased, among which 0.6% EMS treatment had the biggest influence. However, with the same EMS consistency, there was not close relevancy between the amount of mutagenic agent and the divergence of plant's genomes, which offered a molecular basis for selecting plants with good mutation.

  3. Occurrence of Aflatoxin M1 in Dairy Products in Southern Italy

    Directory of Open Access Journals (Sweden)

    Giovanna Barbuti

    2008-12-01

    Full Text Available A screening survey of the presence of aflatoxin M1 (AFM1 was carried out on 265 samples of cheese made from cow, buffalo, goat, sheep, sheep-goat milk collected in the Apulia region (Southern Italy. Selected samples included unripened, medium and long-term ripened cheeses. AFM1 was found in 16.6% of the analyzed samples. The highest positive incidence was for medium and long-term ripened cheeses, especially those made from sheep-goat milk, while buffalo cheeses tested consistently negative. Our results show that the level of contamination by AFM1 in dairy products from Apulia Region are lower than in other Italian and European regions. Moreover, it is important to underline that a common European norm concerning the AFM1 threshold limits for dairy products is still lacking.

  4. An Automatic Detection Method of Nanocomposite Film Element Based on GLCM and Adaboost M1

    Directory of Open Access Journals (Sweden)

    Hai Guo

    2015-01-01

    Full Text Available An automatic detection model adopting pattern recognition technology is proposed in this paper; it can realize the measurement to the element of nanocomposite film. The features of gray level cooccurrence matrix (GLCM can be extracted from different types of surface morphology images of film; after that, the dimension reduction of film can be handled by principal component analysis (PCA. So it is possible to identify the element of film according to the Adaboost M1 algorithm of a strong classifier with ten decision tree classifiers. The experimental result shows that this model is superior to the ones of SVM (support vector machine, NN and BayesNet. The method proposed can be widely applied to the automatic detection of not only nanocomposite film element but also other nanocomposite material elements.

  5. The M/M/1 Queue with Controlled Multiple Working Vacations

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-bo; FENG Ping-hua

    2013-01-01

    In this paper,we study an M/M/1 queue with multiple working vacations under following Bernoulli control policy:at the instants of the completion of a service in vacation,the server will interrupt the vacation and enter regular busy period with probabiiity1-p (if there are customers in the queue) or continue the vacation with probability p.For this model,we drive the analytic expression of the stationary queue length and demonstrate stochastic decomposition structures of the stationary queue length and waiting time,also we obtain the additional queue length and the additional delay of this model.The results we got agree with the corresponding results for working vacation model with or without vacation interruption if we set p =0 or p =1,respectively.

  6. Detection of Aflatoxin M1 in Milk from Qom (Aried and Semiaried Province of Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Dakhili

    2016-06-01

    Full Text Available Background: Aflatoxins are secondary metabolites fungal When animals consume contaminated feed stuff to Aflatoxin B1 (AFB1, the toxin hydrolyzed and changed to the aflatoxin M1 and transmit to the milk consumers. Methods: seventy milk samples from different milk producers who were selling their milk to the dairy plant during two season in winter and summer and investigated by Enzyme Linked Immuno Sorbent Assay (ELISA. Results: AFM1 was found in 100% of the milk samples in winter. About 15% of the samples had AFM1 greater than the maximum tolerance limit (50ng/l accepted by European Union. Mean concentrations of AFM1 in Winter, Summer were 122, 53 ng/L, respectively. Mean concentrations of AFM1 in winter and Summer samples were significantly higher (P<0.05. Conclusion: these results show that the important of periodically monitoring the occurrence of AFM1 in raw milk and dairy products in Qom province.

  7. Fluid queues driven by an M/M/1/N queue

    Directory of Open Access Journals (Sweden)

    R. B. Lenin

    2000-01-01

    Full Text Available In this paper, we consider fluid queue models with infinite buffer capacity which receives and releases fluid at variable rates in such a way that the net input rate of fluid into the buffer (which is negative when fluid is flowing out of the buffer is uniquely determined by the number of customers in an M/M/1/N queue model (that is, the fluid queue is driven by this Markovian queue with constant arrival and service rates. We use some interesting identities of tridiagonal determinants to find analytically the eigenvalues of the underlying tridiagonal matrix and hence the distribution function of the buffer occupancy. For specific cases, we verify the results available in the literature.

  8. Scaled-energy spectroscopy of a |M|=1 Rydberg barium atom in an electric field

    Institute of Scientific and Technical Information of China (English)

    Wang Lei; Quan Wei; Shen Li; Yang Hai-Feng; Shi Ting-Yun; Liu Xiao-Jun; Liu Hong-Ping; Zhan Ming-Sheng

    2009-01-01

    We observe strong energy-dependent quantum defects in the scaled-energy Stark spectra for |M|=1 Rydberg states of barium atoms at three scaled energies: ε= -2.000, ε= -2.500 and ε=-3.000. In an attempt to explain the observations, theoretical calculations of closed orbit theory based on a model potential including core effect are performed for non-hydrogenic atoms. While such a potential has been uniformly successful for alkali atoms with a single valence electron, it fails to match experimental results for barium atoms in the 6snp Rydberg states with two valence electrons. Our study points out that this discrepancy is due to the strong perturbation from the 5d8p state, which voids the simple approximation for constant quantum defects of principle quantum number n.

  9. E1M1 and E1E2 transition probabilities in one-electron ions

    Energy Technology Data Exchange (ETDEWEB)

    Labzowsky, L.N. [Institute of Physics, St. Petersburg State University, Uljanovskaya 1, Petrodvorets, 198904 St. Petersburg (Russian Federation) and Petersburg Nuclear Physics Institute, Gatchina, 188350 St. Petersburg (Russian Federation)]. E-mail: leonti@landau.phys.spbu.ru; Shonin, A.V. [Institute of Physics, St. Petersburg State University, Uljanovskaya 1, Petrodvorets, 198904 St. Petersburg (Russian Federation)

    2004-12-06

    The quantum electrodynamical (QED) theory of the two-photon transitions in hydrogenlike ions is presented. The emission probability for 2s1/2->2{gamma}(E1)+1s1/2 transitions is calculated and compared to the results of the previous calculations. The emission probabilities 2p1/2->{gamma}(E1)+{gamma}(E2)+1s1/2 and 2p1/2->{gamma}(E1)+{gamma}(M1)+1s1/2 are also calculated for the nuclear charge Z values 1=

  10. Remarks on the BRST-cohomology for $c_M > 1$ matter coupled to ``Liouville gravity"

    CERN Document Server

    Bilal, Adel

    1992-01-01

    We describe the (chiral) BRST-cohomology of matter with central charge $10$) and ghost-numbers 0 or $-1$ (for $r<0$). The (chiral) ground ring is isomorphic to a subring of the $c_M =1$ theory which is $(xy)^n,\\ n=0,1,2,\\ldots$, and there are {\\it no} non-trivial currents acting on the ground ring. In case b) there is no non-trivial relative cohomology for non-zero ghost numbers and, for zero ghost number, the cohomology groups are isomorphic to a $(D-1)$-dimensional on-shell ``transverse" Fock space. The only exceptions are at level 1 for vanishing matter momentum and $p_L=Q_L(1+r)$ with $r=\\pm 1$, where one has one more ghost-number zero and a ghost-number $r$ cohomology state. All these results follow quite easily from the existing literature.

  11. BRST cohomology ring in $\\widehat{c}_{M}$ $<$ 1 NSR string theory

    CERN Document Server

    Panda, S; Panda, Sudhakar; Roy, Shibaji

    1995-01-01

    The full cohomology ring of the Lian-Zuckerman type operators (states) in {\\hat c_M}<1 Neveu-Schwarz-Ramond (NSR) string theory is argued to be generated by three elements x, y and w in analogy with the corresponding results in the bosonic case. The ground ring generators x and y are non-invertible and belong to the Ramond sector whereas the higher ghost number operators are generated by an invertible element w with ghost number one less than that of the ground ring generators and belongs to either Neveu-Schwarz (NS) or Ramond (R) sector depending on whether we consider (even, even) or (odd, odd) series coupled to 2d supergravity. We explicitly construct these operators (states) and illustrate our result with an example of pure Liouville supergravity.

  12. Genotype × genotype interactions between the toxic cyanobacterium Microcystis and its grazer, the waterflea Daphnia

    Science.gov (United States)

    Lemaire, Veerle; Brusciotti, Silvia; van Gremberghe, Ineke; Vyverman, Wim; Vanoverbeke, Joost; De Meester, Luc

    2012-01-01

    Toxic algal blooms are an important problem worldwide. The literature on toxic cyanobacteria blooms in inland waters reports widely divergent results on whether zooplankton can control cyanobacteria blooms or cyanobacteria suppress zooplankton by their toxins. Here we test whether this may be due to genotype × genotype interactions, in which interactions between the large-bodied and efficient grazer Daphnia and the widespread cyanobacterium Microcystis are not only dependent on Microcystis strain or Daphnia genotype but are specific to genotype × genotype combinations. We show that genotype × genotype interactions are important in explaining mortality in short-time exposures of Daphnia to Microcystis. These genotype × genotype interactions may result in local coadaptation and a geographic mosaic of coevolution. Genotype × genotype interactions can explain why the literature on zooplankton–cyanobacteria interactions is seemingly inconsistent, and provide hope that zooplankton can contribute to the suppression of cyanobacteria blooms in restoration projects. PMID:25568039

  13. The Matrix protein M1 from influenza C virus induces tubular membrane invaginations in an in vitro cell membrane model

    Science.gov (United States)

    Saletti, David; Radzimanowski, Jens; Effantin, Gregory; Midtvedt, Daniel; Mangenot, Stéphanie; Weissenhorn, Winfried; Bassereau, Patricia; Bally, Marta

    2017-01-01

    Matrix proteins from enveloped viruses play an important role in budding and stabilizing virus particles. In order to assess the role of the matrix protein M1 from influenza C virus (M1-C) in plasma membrane deformation, we have combined structural and in vitro reconstitution experiments with model membranes. We present the crystal structure of the N-terminal domain of M1-C and show by Small Angle X-Ray Scattering analysis that full-length M1-C folds into an elongated structure that associates laterally into ring-like or filamentous polymers. Using negatively charged giant unilamellar vesicles (GUVs), we demonstrate that M1-C full-length binds to and induces inward budding of membrane tubules with diameters that resemble the diameter of viruses. Membrane tubule formation requires the C-terminal domain of M1-C, corroborating its essential role for M1-C polymerization. Our results indicate that M1-C assembly on membranes constitutes the driving force for budding and suggest that M1-C plays a key role in facilitating viral egress. PMID:28120862

  14. Sequence Characterization of matrix protein (M1 in influenza A viruses (H1, H3 and H5

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2011-10-01

    Full Text Available This study brings the analysis of amino acid sequences of matrix protein (M1 from the influenza virus A (H1N1, H3N2 and H5N1 during 2007-2208. 741 sequences of M1 were compared, of them, H1N1 388; H3N2 251 and H5N1 102. Even though, the M1 is relatively conserved among the influenza A viruses, we found some variations in the M1 among the viruses, H1N1, H3N2 and H5N1. The nuclear localization signal at amino acid 101 to 105 is RKLKR for H1N1 and H3N2, but for H5N1 is KKLKR. All differences of amino acid in M1 of H1, H3 and H5 were listed. 80 sequences of M1 of H1N1 H3N2 and H5N1 were used for phylogenetic analysis. There is no reasontantment found in the M1 among these subtypes. Further study is needed to study the differences of the function of M1 among H1N1, H3N2 and H5N1. The M1 of H5N1 may contribute to the high pathogenesis to this virus.

  15. Seasonal milk contamination by aflatoxin m1, organophosphates and carbamates in Paraná – Brazil

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Crispim de Oliveira Ramos

    2016-08-01

    Full Text Available Aiming to evaluate the milk contamination in the dairy production systems (DPS for mycotoxins and chemical residues of organophosphates and carbamates it was made a study encompassing 96 DPS in three regions of Parana state. There were collected samples of milk, water and food and they were evaluated for chemical residues in all samples and aflatoxin only for food and milk. Mycotoxins in food (aflatoxin B1, B2, G1, G2, zearalenone and ochratoxin were detected by the method of thin layer chromatography – TLC and for the determination of aflatoxin M1 was used an immunoassay kit competitive ELISA Ridascreen®. The residues of organophosphates and carbamates were performed by colorimetric method qualitatively. There were evaluated the differences between regions, periods and the sources of mycotoxin contamination. Carbamates and organophosphates were screened for their presence in milk and the sources of food and water. Then it was estimated the contributions of each mycotoxin for milk contamination, as well as their respective contaminated food. Differences were found between periods (p < 0,05 for milk contamination with aflatoxin M1 – AFM1. For carbamates and organophosphates were found different contamination sources (p < 0,01. For the carbamates the source were pesticides used to parasitic herd control and for the organophosphates pesticides used in agriculture. For food sources contamination resulting in the AFM1 contamination it was detected that aflatoxin B1 – AFB1 was the main source. The aflatoxin G1 – AFG1 showed a strong correlation (p < 0,01 with AFB1 levels suggesting causal relationship is a function of fungal strains producing both at the same time. It was also found the prevalence of aflatoxin contamination in 70% of contaminated samples and its predominant presence in relation to other mycotoxins in all kinds of foods analyzed. By identifying the checkpoints of contamination can be proposed the inclusion of practical

  16. The frequency of occurrence of aflatoxin M1 in milk on the territory of Vojvodina

    Directory of Open Access Journals (Sweden)

    Polovinski-Horvatović Miroslava S.

    2009-01-01

    Full Text Available Aflatoxin is one of the most common mycotoxins which can be found in milk. It represents a natural metabolite of aflatoxin B1 that occurs as a result of animal metabolism and the body's attempt to detoxificate it. It is excreted in milk, feces and urine of animals that consumed contaminated feed with aflatoxin B1. The carry-over from feed to milk depends on many factors, ranging from 0.3 to 6.2%. Aflatoxin M1 is in the first group of carcinogens according to the IRAC classification from 2002, but it is considered to have only 10% of carcinogenicity from its precursor aflatoxin B1. Legislation in member countries of European Union for this mycotoxin in milk intended for people is 0.05 μg/l, while the rest of the countries that also have legislation for this mycotoxin allow the concentration that is ten times higher, and that is 0.5 μg/l. In this paper, we have tried to provide on insight into the quality of milk, food often consumed by children, from the standpoint of mycotoxicology, and to compare the obtained data with data available from literature, from countries in the region that have similar climatic and agricultural conditions. From a total of 65 samples of processed milk, aflatoxin M1 was found in 18 samples and none of the samples exceeded the level of 0.05 μg/l, which is allowed by the legislation of the European Union.

  17. In Vivo Measurements in Mice in the Bion-M 1 Mission

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Custaud, Marc-Antoine; Popova, Anfisa; Borovik, Anatoliy; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Daria; Vinogradova, Olga

    The main aim of BION-M 1 mission was to reveal morphological, biochemical and molecular mechanisms of adaptation to prolonged exposure in microgravity. Besides that functional state and behavior were assessed in vivo using test battery, home cage observations and implantable telemetry in space-flown mice (SF), control mice from the ground replica of the flight experiment (GC) and in mice kept in vivarium (SFV and GCV). Blood pressure and heart rate were monitored continuously in a subgroup of mice using implantable telemetry throughout the flight as well as before and after it. After 30-days flight aboard BION-M 1 biosatellite SF mice have gained more weight than GC, SFV or GCV mice (11%). SF mice displayed pronounced motor impairment upon examination shortly after landing. 1 day after the flight mice were less active and more anxious in the open-field test, less coordinated in the Rotarod and aerial drop test and had less grip force compared to both control and pre-flight values. Exercise performance was greatly reduced after 30-days flight and recovered by day 7 post-flight. Before the flight mice were trained to perform a simple task using positively reinforced free operant conditioning approach. After the flight performance in the same task was preserved, however learning ability was impaired. Mice displayed drastic reduction of heart rate during launch and reentry acceleration periods. Heart rate (by 8-10%) and, to a lesser extent blood pressure (by 5%) were elevated during the 30-days flight. After return heart rate in SF mice remained elevated throughout the 7-days observation period with no apparent recovery. In summary, mice display pronounced disadaptation to 1g after 30-days exposure in microgravity with different physiological systems having different recovery dynamics. Of particular interest, hemodynamic reactions in mice closely resemble reactions in larger organisms, implying that factors that govern the cardiovascular system adaptation to

  18. The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew.

    Science.gov (United States)

    Cottriall, C L; McBrien, N A

    1996-06-01

    To determine the efficacy of the M1-selective muscarinic antagonist, pirenzepine, in preventing experimentally induced myopia in a mammalian model, the tree shrew. Tree shrews were monocularly deprived (MD) using translucent goggles or negative lenses for a period of 12 days. In two of the MD groups, tree shrews received daily subconjunctival administration of either pirenzepine (17.7 mumol; n = 9) or vehicle control (n = 6). Control groups (n = 6) were used to assess the effects of MD, injection regimen, and drug effects. In sham-injected and saline-injected MD tree shrews, 12 days of MD produced-13.2 D +/- 0.8 D and -14.1 D +/- 0.5 D of axial myopia, respectively. In pirenzepine-injected MD tree shrews, 12 days of MD induced an axial myopia of only -2.1 D +/- 1.4 D. The significant reduction in myopia in pirenzepine-injected MD tree shrews was caused by significantly less vitreous chamber elongation of the deprived eye (0.05 mm +/- 0.04 mm) relative to the contralateral control eye when compared to sham-injected and saline-injected MD tree shrews (0.24 mm +/- 0.02 mm and 0.29 mm +/- 0.01 mm). Mean equatorial enlargement and increased eye weight were prevented in pirenzepine-injected MD tree shrews (P Pirenzepine also was found to reduce myopia and ocular enlargement in lens defocus-induced myopia. Control experiments demonstrated that pirenzepine did not cause a significant reduction in amplitude of carbachol-induced accommodation. Findings demonstrate that chronic administration of the M1-selective muscarinic antagonist, pirenzepine, prevents experimentally induced myopia in this mammalian model by a nonaccommodative mechanism.

  19. Paracoccin Induces M1 Polarization of Macrophages via Interaction with TLR4

    Science.gov (United States)

    Freitas, Mateus S.; Oliveira, Aline F.; da Silva, Thiago A.; Fernandes, Fabrício F.; Gonçales, Relber A.; Almeida, Fausto; Roque-Barreira, Maria C.

    2016-01-01

    The fungal human pathogen Paracoccidioides brasiliensis contains paracoccin (PCN), a multi-domain protein that has lectin and N-acetyl-glucosaminidase activities, which account for its effects on the growth and morphogenesis of the fungus and on the activation of host macrophages through its interaction with TLR N-glycans. With the purpose of detailing the knowledge on the effects of PCN on macrophages, we used recombinant PCN expressed in Pichia pastoris (p-rPCN) to stimulate isolated murine peritoneal macrophages. The activation of these cells manifested through the release of high levels of inflammatory mediators, such as nitric oxide, TNF-α, IL-12p40, and IL-6. Furthermore, peritoneal macrophages stimulated with p-rPCN increased the relative expression of STAT1, SOCS3, and iNOS2 mRNA (M1 polarization markers). However, the expression of Arginase-1, Ym-1, and FIZZ1 (M2 polarization markers) remained at basal levels. Interestingly, the observed M1 macrophages’ polarization triggered by p-rPCN was abolished in cells obtained from knockout Toll-like receptor-4 mice. In this case, the p-rPCN-induced production of pro-inflammatory mediators was blocked too. These results demonstrate that the classical activation of macrophages induced by paracoccin depends on TLR4. Taken together, the results of our study indicate that paracoccin acts as a TLR agonist able to modulate immunity and exerts biological activities that favor its applicability as an immunotherapeutic agent to combat systemic fungal infections. PMID:27458431

  20. Composition of breccia matrices from the Manson M-1 drill core

    Science.gov (United States)

    Kracher, A.; Anderson, R. R.; Koeberl, C.

    1994-07-01

    Eleven drill cores were recently recovered from the Manson, Iowa, impact structure. Core M-1, which was drilled at the edge of the large central uplift, contains three major impact rock types: sedimentary clast breccia, melt matrix breccia, and fragmental breccia. Breccia matrices from different depths in the M-1 core were investigated by defocused beam electron probe microanalysis. To obtain average compositions, matrix areas free of lithic and mineral clasts were covered with an orthogonal grid of analyses points. Variations in composition have two main causes: differences in source lithology and postimpact processes. With increasing depth distinct changes in composition can be observed. All compositions are highly feldspathic and surprisingly low in SiO2 for putative source lithologies of mostly granitic composition. Within the lithological units containing melt matrix breccia increasing recrystallization can be observed with depth. Compositions in this interval are marginally corundum normative and not as high in normative feldspar as other matrices. The thoroughly recrystallized matrices from the lowest intervals of the melt matrix breccia are more feldpathic, higher in Na/K ratio, and not corundum normative. Unlike the chemical variation between rock types, we tentatively ascribe the chemical changes within the melt matrix breccia to reaction of matrix with clasts. In particular, quartz clasts in breccias with highly recrystallized matrices develop fringes of K-spar, cpx, and ilmenite. The formation of these minerals is presumably accompanied by complementary changes in matrix composition. Factor analysis on data sets of individual melt matrix analyses provides further clues to the influence of source lithology and post impact processes respectively in the chemical makeup of the breccia matrices. The most significant factors are a mafic component and a plagioclase component.

  1. Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

    Directory of Open Access Journals (Sweden)

    Federica Raggi

    2017-09-01

    Full Text Available Macrophages (Mf are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1 and alternatively activated (anti-inflammatory M2 subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment.

  2. Echinococcus granulosus sensu lato genotypes infecting humans--review of current knowledge.

    Science.gov (United States)

    Alvarez Rojas, Cristian A; Romig, Thomas; Lightowlers, Marshall W

    2014-01-01

    Genetic variability in the species group Echinococcus granulosus sensu lato is well recognised as affecting intermediate host susceptibility and other biological features of the parasites. Molecular methods have allowed discrimination of different genotypes (G1-10 and the 'lion strain'), some of which are now considered separate species. An accumulation of genotypic analyses undertaken on parasite isolates from human cases of cystic echinococcosis provides the basis upon which an assessment is made here of the relative contribution of the different genotypes to human disease. The allocation of samples to G-numbers becomes increasingly difficult, because much more variability than previously recognised exists in the genotypic clusters G1-3 (=E. granulosus sensu stricto) and G6-10 (Echinococcus canadensis). To accommodate the heterogeneous criteria used for genotyping in the literature, we restrict ourselves to differentiate between E. granulosus sensu stricto (G1-3), Echinococcus equinus (G4), Echinococcus ortleppi (G5) and E. canadensis (G6-7, G8, G10). The genotype G1 is responsible for the great majority of human cystic echinococcosis worldwide (88.44%), has the most cosmopolitan distribution and is often associated with transmission via sheep as intermediate hosts. The closely related genotypes G6 and G7 cause a significant number of human infections (11.07%). The genotype G6 was found to be responsible for 7.34% of infections worldwide. This strain is known from Africa and Asia, where it is transmitted mainly by camels (and goats), and South America, where it appears to be mainly transmitted by goats. The G7 genotype has been responsible for 3.73% of human cases of cystic echinococcosis in eastern European countries, where the parasite is transmitted by pigs. Some of the samples (11) could not be identified with a single specific genotype belonging to E. canadensis (G6/10). Rare cases of human cystic echinococcosis have been identified as having been caused by

  3. 乳品中黄曲霉毒素M1检测方法研究进展%Review on detection methods of aflatoxin M1 in dairy products

    Institute of Scientific and Technical Information of China (English)

    黄亚伟; 魏光; 王若兰; 罗莉

    2014-01-01

    Aflatoxin M1 is the metabolite of aflatoxin B1 after being intaken by animals. It mainly appears in animals’ milk and urine. Aflatoxin M1 is very toxic, ingestion of which by dairy will produce a great harm to the human body. This paper focused on the toxicity, hazards, and detection methods of aflatoxin M1 in dairy. The main characteristics and scope of the detection methods were analyzed and summarized, and the develop-ment of detection of aflatoxin M1 were also reasonably prospected.%黄曲霉毒素M1是动物摄入黄曲霉毒素B1后的代谢产物,主要分布在动物的乳汁、尿液中。黄曲霉毒素 M1毒性很大,经乳制品摄入会对人体产生巨大的危害。本文主要对乳品中黄曲霉毒素 M1毒性、危害、检测方法进行综述。对主要检测方法的特性及适用范围进行分析与概括,并且对未来黄曲霉毒素M1的检测方法的发展进行了合理展望。

  4. Site-specific dephosphorylation of tau of apolipoprotein E-deficient and control mice by M1 muscarinic agonist treatment.

    Science.gov (United States)

    Genis, I; Fisher, A; Michaelson, D M

    1999-01-01

    Apolipoprotein E (apoE)-deficient mice have memory deficits that are associated with synaptic loss of basal forebrain cholinergic projections and with hyperphosphorylation of distinct epitopes of the microtubule-associated protein tau. Furthermore, treatment of apoE-deficient mice with the M1 selective agonist 1-methylpiperidine-4-spiro-(2'-methylthiazoline) [AF150(S)] abolishes their memory deficits and results in recovery of their brain cholinergic markers. In the present study, we used a panel of anti-tau monoclonal antibodies to further map the tau epitopes that are hyperphosphorylated in apoE-deficient mice and examined the effects of prolonged treatment with AF150(S). This revealed that tau of apoE-deficient mice contains a distinct, hyperphosphorylated "hot spot" domain which is localized N-terminally to the microtubule binding domain of tau, and that AF150(S) has an epitope-specific tau dephosphorylating effect whose magnitude is affected by apoE deficiency. Accordingly, epitopes which reside in the hyperphosphorylated "hot spot" are dephosphorylated by AF150(S) in apoE-deficient mice but are almost unaffected in the controls, whereas epitopes which flank this tau domain are dephosphorylated by AF150(S) in both mice groups. In contrast, epitopes located at the N and C terminals of tau are unaffected by AF150(S) in both groups of mice. These findings suggest that apoE deficiency results in hyperphosphorylation of a distinct tau domain whose excess phosphorylation can be reduced by muscarinic treatment.

  5. Obesity Contributes to Ovarian Cancer Metastatic Success through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages.

    Science.gov (United States)

    Liu, Yueying; Metzinger, Matthew N; Lewellen, Kyle A; Cripps, Stephanie N; Carey, Kyle D; Harper, Elizabeth I; Shi, Zonggao; Tarwater, Laura; Grisoli, Annie; Lee, Eric; Slusarz, Ania; Yang, Jing; Loughran, Elizabeth A; Conley, Kaitlyn; Johnson, Jeff J; Klymenko, Yuliya; Bruney, Lana; Liang, Zhong; Dovichi, Norman J; Cheatham, Bentley; Leevy, W Matthew; Stack, M Sharon

    2015-12-01

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intraperitoneal metastases. Recent meta-analyses report an association between obesity, ovarian cancer incidence, and ovarian cancer survival, but the effect of obesity on metastasis has not been evaluated. The objective of this study was to use an integrative approach combining in vitro, ex vivo, and in vivo studies to test the hypothesis that obesity contributes to ovarian cancer metastatic success. Initial in vitro studies using three-dimensional mesomimetic cultures showed enhanced cell-cell adhesion to the lipid-loaded mesothelium. Furthermore, in an ex vivo colonization assay, ovarian cancer cells exhibited increased adhesion to mesothelial explants excised from mice modeling diet-induced obesity (DIO), in which they were fed a "Western" diet. Examination of mesothelial ultrastructure revealed a substantial increase in the density of microvilli in DIO mice. Moreover, enhanced intraperitoneal tumor burden was observed in overweight or obese animals in three distinct in vivo models. Further histologic analyses suggested that alterations in lipid regulatory factors, enhanced vascularity, and decreased M1/M2 macrophage ratios may account for the enhanced tumorigenicity. Together, these findings show that obesity potently affects ovarian cancer metastatic success, which likely contributes to the negative correlation between obesity and ovarian cancer survival. ©2015 American Association for Cancer Research.

  6. Glutamine synthetase in Durum Wheat: Genotypic Variation and Relationship with Grain Protein Content.

    Science.gov (United States)

    Nigro, Domenica; Fortunato, Stefania; Giove, Stefania L; Paradiso, Annalisa; Gu, Yong Q; Blanco, Antonio; de Pinto, Maria C; Gadaleta, Agata

    2016-01-01

    Grain protein content (GPC), is one of the most important trait in wheat and its characterized by a very complex genetic control. The identification of wheat varieties with high GPC (HGPC), as well as the characterization of central enzymes involved in these processes, are important for more sustainable agricultural practices. In this study, we focused on Glutamine synthetase (GS) as a candidate to study GPC in wheat. We analyzed GS expression and its enzymatic activity in different tissues and phenological stages in 10 durum wheat genotypes with different GPC. Although each genotype performed quite differently from the others, both because their genetic variability and their adaptability to specific environmental conditions, the highest GS activity and expression were found in genotypes with HGPC and vice versa the lowest ones in genotypes with low GPC (LGPC). Moreover, in genotypes contrasting in GPC bred at different nitrogen regimes (0, 60, 140 N Unit/ha) GS behaved differently in diverse organs. Nitrogen supplement increased GS expression and activity in roots of all genotypes, highlighting the key role of this enzyme in nitrogen assimilation and ammonium detoxification in roots. Otherwise, nitrogen treatments decreased GS expression and activity in the leaves of HGPC genotypes and did not affect GS in the leaves of LGPC genotypes. Finally, no changes in GS and soluble protein content occurred at the filling stage in the caryopses of all analyzed genotypes.

  7. Variable salinity responses of 12 alfalfa genotypes and comparative expression analyses of salt-response genes

    Science.gov (United States)

    Sandhu, Devinder; Cornacchione, Monica V.; Ferreira, Jorge F. S.; Suarez, Donald L.

    2017-01-01

    Twelve alfalfa genotypes that were selected for biomass under salinity, differences in Na and Cl concentrations in shoots and K/Na ratio were evaluated in this long-term salinity experiment. The selected plants were cloned to reduce genetic variability within each genotype. Salt tolerance (ST) index of the genotypes ranged from 0.39 to 1. The most salt-tolerant genotypes SISA14-1 (G03) and AZ-90ST (G10), the top performers for biomass, exhibited the least effect on shoot number and height. SISA14-1 (G03) accumulated low Na and Cl under salinity. Most genotypes exhibited a net reduction in shoot Ca, Mg, P, Fe, and Cu, while Mn and Zn increased under salinity. Salinity reduced foliar area and stomatal conductance; while net photosynthetic rate and transpiration were not affected. Interestingly, salinity increased chlorophyll and antioxidant capacity in most genotypes; however neither parameter correlated well to ST index. Salt-tolerant genotypes showed upregulation of the SOS1, SOS2, SOS3, HKT1, AKT1, NHX1, P5CS1, HSP90.7, HSP81.2, HSP71.1, HSPC025, OTS1, SGF29 and SAL1 genes. Gene expression analyses allowed us to classify genotypes based on their ability to regulate different components of the salt tolerance mechanism. Pyramiding different components of the salt tolerance mechanism may lead to superior salt-tolerant alfalfa genotypes. PMID:28225027

  8. 叉头框蛋白 M1在乳腺癌的进展及治疗耐药中的作用%The role of FoxM1 in the development and treatment of breast cancer

    Institute of Scientific and Technical Information of China (English)

    李蕙颖(综述); 耿敬姝(审校)

    2016-01-01

    FoxM1 is a specific transcription factor related to proliferation .Previous studies have found that FoxM1 can enhance the proliferation ,metastasis and invasion of cancer cells ,and play a crucial role in canc-er.Recent studies indicate that the abnormal expression of FoxM 1 plays an important role in breast cancer ,and its overexpression is negatively correlated with the overall survival of patients .For the early diagnosis of breast canc-er,clinical prognosis and study on combination therapy provides a new direction .This article reviews the relation-ship between FoxM1 and breast cancer .%叉头框蛋白质M1(Forkhead box protein M1,FoxM1)是一种特异性的与增殖相关的转录因子。既往研究发现,FoxM1具有增强癌细胞增殖、转移和侵袭的功能,在肿瘤的发生发展中扮演着至关重要的角色。近年来研究表明,FoxM1的异常表达在乳腺癌的发生及发展中起着重要的作用,且其过表达与肿瘤患者的总生存期的关系呈负相关,为乳腺癌的早期诊断、临床预后及联合治疗提供了新的研究方向,本文就FoxM1与乳腺癌的关系做一综述。

  9. Assessment of the association between GSTM1 null genotype and risk of type 2 diabetes.

    Science.gov (United States)

    Yi, Ran; Liu, Bin; Dong, Qi

    2013-06-01

    Many studies have investigated the association between Glutathione S-Transferase M1 (GSTM1) null genotype and risk of diabetes mellitus, but the impact of GSTM1 null genotype on diabetes mellitus is unclear owing to the obvious inconsistence among those studies. This study aimed to quantify the strength of association between GSTM1 null genotype and risk of diabetes mellitus. We searched the PubMed, Embase and Wangfang databases for studies relating the association between GSTM1 null genotype and risk of diabetes mellitus. We estimated summary odds ratio (OR) with their 95 % confidence interval (95 % CI) to assess the association. Subgroup analyses were performed by type of diabetes and ethnicity. 10 case-control studies with 7, 054 subjects were included into this meta-analysis. Meta-analysis of total 10 studies showed GSTM1 null genotype was associated increased risk of diabetes mellitus (OR = 1.59, 95 % CI 1.14-2.22, P = 0.007). Subgroup analyses by type of diabetes mellitus suggested GSTM1 null genotype was associated increased risk of type 2 diabetes (OR = 1.90, 95 % CI 1.37-2.64, P null genotype and increased risk of type 2 diabetes. The cumulative meta-analyses showed a trend of obvious association between GSTM1 null genotype and risk of type 2 diabetes as information accumulated. No evidence of publication bias was observed. Thus, evidence from current meta-analysis suggests an association between GSTM1 null genotype and risk of type 2 diabetes.

  10. Influence of genotyping error in linkage mapping for complex traits – an analytic study

    Directory of Open Access Journals (Sweden)

    van Houwelingen Hans C

    2008-08-01

    Full Text Available Abstract Background Despite the current trend towards large epidemiological studies of unrelated individuals, linkage studies in families are still thoroughly being utilized as tools for disease gene mapping. The use of the single-nucleotide-polymorphisms (SNP array technology in genotyping of family data has the potential to provide more informative linkage data. Nevertheless, SNP array data are not immune to genotyping error which, as has been suggested in the past, could dramatically affect the evidence for linkage especially in selective designs such as affected sib pair (ASP designs. The influence of genotyping error on selective designs for continuous traits has not been assessed yet. Results We use the identity-by-descent (IBD regression-based paradigm for linkage testing to analytically quantify the effect of simple genotyping error models under specific selection schemes for sibling pairs. We show, for example, that in extremely concordant (EC designs, genotyping error leads to decreased power whereas it leads to increased type I error in extremely discordant (ED designs. Perhaps surprisingly, the effect of genotyping error on inference is most severe in designs where selection is least extreme. We suggest a genomic control for genotyping errors via a simple modification of the intercept in the regression for linkage. Conclusion This study extends earlier findings: genotyping error can substantially affect type I error and power in selective designs for continuous traits. Designs involving both EC and ED sib pairs are fairly immune to genotyping error. When those designs are not feasible the simple genomic control strategy that we suggest offers the potential to deliver more robust inference, especially if genotyping is carried out by SNP array technology.

  11. Epidemiological and Clinical Features of Hepatitis B Virus Genotypes among Immigrants in Southern Italy

    Directory of Open Access Journals (Sweden)

    Gaetano Scotto

    2010-01-01

    Full Text Available Background/aims. This study aims to determine the distribution and clinical features of HBV-genotypes in a population of immigrants affected by HBV-infection. Methods. Between 01/2003 and 03/2009, 1623 immigrants were tested for HBV-infection. Biochemical and virological activities were determined in HBsAg-positive patients; HBV-genotypes were determined, by the INNO-LiPA HBV Genotyping, in the subjects with HBV DNA detectable. In every patient we evaluated the stage and classified the infection as inactive carrier, mild or moderate/severe chronic hepatitis, cirrhosis, and/or HCC. Results. Among the tested subjects, 191 (11.7% resulted HBsAg-positive, and in 144/191 (75.4% serum HBV-DNA was detectable. The genotype distribution was as follows: 45,13% genotype E, 18,1% genotype D, 15,3% genotype B, 13,2% genotype C, 4,9% genotype A, 3,5% mixed genotypes (A–D. The evaluation of liver disease degree showed that 24.6% patients were inactive carriers of HBV infection, 19.4% presented a immunotolerance phase, 34.5% had mild chronic hepatitis, 13.6% had a moderate/severe chronic hepatitis, 6.3% had cirrhosis, and 1.6% presented HCC. Conclusions. Our study evidences a high prevalence of HBV-infection in immigrants, and the potentiality of migratory flow in the introduction of genotype non-D hepatitis B virus. The Hepatitis B virus genotypes presented significant differences in epidemiological and clinical characteristics.

  12. FTO genotype and weight loss

    DEFF Research Database (Denmark)

    Livingstone, Katherine M; Celis-Morales, Carlos; Papandonatos, George D;

    2016-01-01

    OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURCES...... well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015969.......: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after...

  13. Two-mode clustering of genotype by trait and genotype by environment data

    NARCIS (Netherlands)

    Hageman, J.A.; Malosetti, M.; Eeuwijk, van F.A.

    2012-01-01

    In this paper, we demonstrate the use of two-mode clustering for genotype by trait and genotype by environment data. In contrast to two separate (one mode) clusterings on genotypes or traits/environments, two-mode clustering simultaneously produces homogeneous groups of genotypes and traits/environm

  14. The preparation of milkpowder contaminated with aflatoxin M1. Investigations of the homogeneity and stability of the product

    NARCIS (Netherlands)

    Egmond; H.P.van; Sizoo; E.A.

    1984-01-01

    Ten behoeve van BCR werd een hoeveelheid melkpoeder bereid, langs natuurlijke weg besmet met aflatoxine M1 op een niveau van ca. 1 mug/kg. Onderzoek naar de homogeniteit van het materiaal wees uit dat aflatoxine M1 homogeen verdeeld was over de geproduceerde melkpoeder. Voorts bleek dat beware

  15. Selection of common bean (Phaseolus vulgaris L.) genotypes using a genotype plus genotype x environment interaction biplot.

    Science.gov (United States)

    Corrêa, A M; Teodoro, P E; Gonçalves, M C; Santos, A; Torres, F E

    2016-08-05

    Recently, the genotype plus genotype x environment interaction (GGE) biplot methodology has been used to investigate genotype x environment interactions in several crop species, but has not been applied to the common bean (Phaseolus vulgaris L.) crop in Brazil. The aim of this study was to identify common bean genotypes that exhibit high grain yield and stability in the State of Mato Grosso do Sul, Brazil. We conducted 12 trials from 2000 to 2006 in the municipalities of Aquidauana and Dourados, and evaluated 13 genotypes in a randomized block design with three replications. Grain yield data were subjected to individual and joint analyses of variance. After analyzing the GE interaction, the adaptability and phenotypic stability of the common bean genotypes were analyzed using GGE biplot methodology. The genotypes EMGOPA-201, Xamego, and Aporé are recommended for growing in Mato Grosso do Sul, because they exhibited high grain yield and phenotypic stability.

  16. Nuclear export of the influenza virus ribonucleoprotein complex: Interaction of Hsc70 with viral proteins M1 and NS2.

    Science.gov (United States)

    Watanabe, Ken; Shimizu, Teppei; Noda, Saiko; Tsukahara, Fujiko; Maru, Yoshiro; Kobayashi, Nobuyuki

    2014-01-01

    The influenza virus replicates in the host cell nucleus, and the progeny viral ribonucleoprotein complex (vRNP) is exported to the cytoplasm prior to maturation. NS2 has a nuclear export signal that mediates the nuclear export of vRNP by the vRNP-M1-NS2 complex. We previously reported that the heat shock cognate 70 (Hsc70) protein binds to M1 protein and mediates vRNP export. However, the interactions among M1, NS2, and Hsc70 are poorly understood. In the present study, we demonstrate that Hsc70 interacts with M1 more strongly than with NS2 and competes with NS2 for M1 binding, suggesting an important role of Hsc70 in the nuclear export of vRNP.

  17. F-box protein FBXL2 inhibits gastric cancer proliferation by ubiquitin-mediated degradation of forkhead box M1.

    Science.gov (United States)

    Li, Liang-qing; Pan, Dun; Chen, Hui; Zhang, Lin; Xie, Wen-jun

    2016-02-01

    F-box/LRR-repeat protein 2 (FBXL2), a component of Skp-Cullin-F box (SCF) ubiquitin E3 ligase, has been shown to inhibit tumorigenesis by targeting and ubiquitinating several oncoproteins. However, its role in gastric cancer remains poorly understood. Here, by tandem mass spectrometry, we show that FBXL2 interacts with forkhead box M1 (FoxM1) transcription factor. As a result, FBXL2 promotes ubiquitination and degradation of FoxM1 in gastric cancer cells. Furthermore, overexpression of FBXL2 inhibits, while its deficiency promotes cell proliferation and invasion. Expression levels of cell-cycle regulators (Cdc25B and p27), which are down-stream target effectors of FoxM1, are also regulated by FBXL2. Therefore, our results uncover a previous unknown network involving FBXL2 and FoxM1 in the regulation of gastric cancer growth.

  18. Targeting Rac1 signaling inhibits streptococcal M1 protein-induced CXC chemokine formation, neutrophil infiltration and lung injury.

    Directory of Open Access Journals (Sweden)

    Songen Zhang

    Full Text Available Infections with Streptococcus pyogenes exhibit a wide spectrum of infections ranging from mild pharyngitis to severe Streptococcal toxic shock syndrome (STSS. The M1 serotype of Streptococcus pyogenes is most commonly associated with STSS. In the present study, we hypothesized that Rac1 signaling might regulate M1 protein-induced lung injury. We studied the effect of a Rac1 inhibitor (NSC23766 on M1 protein-provoked pulmonary injury. Male C57BL/6 mice received NSC23766 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Treatment with NSC23766 decreased M1 protein-induced neutrophil infiltration, edema formation and tissue injury in the lung. M1 protein challenge markedly enhanced Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Rac1 activity had no effect on M1 protein-induced expression of Mac-1 on neutrophils. However, Rac1 inhibition markedly decreased M1 protein-evoked formation of CXC chemokines in the lung. Moreover, NSC23766 completely inhibited M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. We conclude that these novel results suggest that Rac1 signaling is a significant regulator of neutrophil infiltration and CXC chemokine production in the lung. Thus, targeting Rac1 activity might be a potent strategy to attenuate streptococcal M1 protein-triggered acute lung damage.

  19. Contamination profile of aflatoxin M1 residues in milk supply chain of Sindh, Pakistan

    Directory of Open Access Journals (Sweden)

    Sana Jawaid

    2015-01-01

    Full Text Available Aflatoxin M1 (AFM1 is a potent carcinogen, teratogen and mutagen found in the milk when lactating animals consume feed contaminated with aflatoxin B1 (AFB1. In the present study, the contamination of AFM1 was evaluated in the milk supply chain of the province of Sindh, Pakistan. For the broader profiling of targeted toxin, enzyme-linked immunosorbent assay (ELISA was used for the determination of AFM1 in both branded and non-branded milk samples. The results showed that 96.43% of samples (81 out of 84 were contaminated with AFM1 in the range of 0.01–0.76 μg/L. The average contamination level was 0.38 μg/L. The determined values of AFM1 in the collected milk samples were above the standard limit of the European Commission while 70% of the samples exceeded levels established by United States regulations. According to these results, the estimated daily intake of AFM1 for adults was determined as 3.1 ng/kg of body weight per day.

  20. Aflatoxin M1 levels in raw milk, pasteurised milk and infant formula

    Directory of Open Access Journals (Sweden)

    Sharaf S. Omar

    2016-06-01

    Full Text Available The incidence of contamination of aflatoxin M1 (AFM1 in milk samples collected from the Jordanian market was investigated by using the competitive enzyme linked immunosorbent assay (ELISA technique. A total of 175 samples were collected during 2014-2015. All tested samples were contaminated with various levels of AFM1 ranging from 9.71 to 288.68 ng/kg. The concentration of AFM1 in 66% of fresh milk samples was higher than the maximum tolerance limit accepted by the European Union (50 ng/kg and 23% higher than the maximum tolerance limit accepted by the US (500 ng/kg. Percentages of contaminated raw cow, sheep, goat and camel milk exceeding the European tolerance limit were 60, 85, 75 and 0%, respectively. Of AFM1 contaminated pasteurised cow milk samples, 12% exceeded the European tolerance limit with a range of contamination between 14.60 and 216.78 ng/kg. For infant formula samples, the average concentration of AFM1 was 120.26 ng/kg (range from 16.55 to 288.68 ng/kg, the concentration of AFM1 in 85% of infant formula samples was higher than the maximum tolerance limit accepted by the European Union and the US (25 ng/kg.

  1. Dose Measurements on the BION-M1 satellite applying passive detector packages

    Science.gov (United States)

    Stradi, Andrea; Berger, Thomas; Kodaira, Satoshi; Kubancak, Jan; Palfalvi, Jozsef K.; Ambrozova, Iva; Tolochek, Raisa; Shurshakov, Vyacheslav; Szabo, Julianna

    A passive detector package was developed in the past years in the Centre for Energy Research, Hungarian Academy of Science to detect cosmic ray particles, to determine their flux and dose. It consists of thermoluminescent detectors (TLD) and plastic solid state nuclear track detectors (SSNTD). In the frame of a scientific co-operation between the Institute for Biomedical Problems (IBMP) fourteen packages were flow within the new BION-M1 satellite program together with biological samples and detector packages from other participants. Two packages were located outside and the rest ones inside the recoverable capsule. Comparing to the previous BION and similar FOTON experiments, (all together 17 successful ones), this flight was a “champion” with the highest altitude (575 km), orbital inclination (64.9°) and flight duration (30 days). The external exposure provided a unique possibility to study not only the elevated level of cosmic rays but also the behavior of the detector packages in extreme circumstances as low temperature and pressure. The paper will summarize the construction of the detector packages, the calibration and evaluation processes, as well as, the linear energy transfer (LET) spectra, the absorbed dose and the mean quality factor. These quantities will be compared taking into consideration their location inside and outside the capsule and to the results of other participants. Also some comparison of results to the previous BION and FOTON flights and contemporary measurements on the ISS will be presented.

  2. Development of an Electrochemical Biosensor for the Detection of Aflatoxin M1 in Milk

    Directory of Open Access Journals (Sweden)

    Jean-Louis Marty

    2010-10-01

    Full Text Available We have developed an electrochemical immunosensor for the detection of ultratrace amounts of aflatoxin M1 (AFM1 in food products. The sensor was based on a competitive immunoassay using horseradish peroxidase (HRP as a tag. Magnetic nanoparticles coated with antibody (anti-AFM1 were used to separate the bound and unbound fractions. The samples containing AFM1 were incubated with a fixed amount of antibody and tracer [AFM1 linked to HRP (conjugate] until the system reached equilibrium. Competition occurs between the antigen (AFM1 and the conjugate for the antibody. Then, the mixture was deposited on the surface of screen-printed carbon electrodes, and the mediator [5-methylphenazinium methyl sulphate (MPMS] was added. The enzymatic response was measured amperometrically. A standard range (0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, 0.3, 0.4 and 0.5 ppb of AFM1-contaminated milk from the ELISA kit was used to obtain a standard curve for AFM1. To test the detection sensitivity of our sensor, samples of commercial milk were supplemented at 0.01, 0.025, 0.05 or 0.1 ppb with AFM1. Our immunosensor has a low detection limit (0.01 ppb, which is under the recommended level of AFM1 [0.05 µg L-1 (ppb], and has good reproducibility.

  3. DETECTION OF AFLATOXIN M1 IN BULK-TANK MILK AND SHEEP CHEESE

    Directory of Open Access Journals (Sweden)

    F. Cossu

    2011-01-01

    Full Text Available The Aflatoxin M1 (AFM1 content in 118 bulk-tank sheep milk samples was evaluated using an ELISA commercial kit. During a lactation, three bulk-tank milk samples were collected from each of 40 semi-extensive farms, selected on the basis of high level of concentrate supplementation as risk factor for exposure to Aflatoxin B1 (AFB1. The AFM1 content was also determined in 38 sheep cheese samples collected from a dairy plant where the farms enrolled in the survey shipped the milk. In the three sampling the concentrate supplementation recorded in the farms ranged between (mean±sd 492.2±257.7 and 397.7±214.3. AFM1 was detected in 1 bulk-tank sheep milk sample (0.8% at concentrations as little as 5.2 ng/L while in 117 it was not detectable (<5 ng/L. AFM1 was also detected in 5 (13.2% out of 38 samples of ripened sheep cheese at levels (mean±sd of 58.1±7.8 ng/Kg. A very low AFM1 content in bulk mik and cheese was observed, as the result of the implementation of good agricultural and good farming practices.

  4. Microwave Emission of Supra-arcade Structure associated with M1.6 Limb Flare

    CERN Document Server

    Kim, Sujin; Shibasaki, Kiyoto; Reznikova, Veronika

    2012-01-01

    We have investigated a supra-arcade structure, associated with an M1.6 flare, which occurred on the south-east limb on 4th of November 2010. It is observed in microwaves at 17 GHz with the Nobeyama Radioheliograph (NoRH), soft X-rays in the range of 8-20 keV with the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI), and EUV with the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO). As reported by Reeves & Golub (2011), the supra-arcade structure is observed predominantly in the AIA 131 {\\AA} channel, which contains a hot 11 MK component from Fe XIX (Boerner et al. 2011). While this hot flare plasma lasts over the decay phase of the flare, it shows some interesting characteristics in microwaves and soft X-rays: 1) In the supra-arcade structure, the brightness temperature (TB) of the microwave emission increases gradually up to 2\\times10^4 K, and 2) two soft X-ray sources appear: one cospatial with the supra-arcade structure and another above the post-flare arcade...

  5. Green pigment from Bacillus cereus M(1)(16) (MTCC 5521): production parameters and antibacterial activity.

    Science.gov (United States)

    Banerjee, Debopam; Chatterjee, Sandipan; Banerjee, U C; Guha, Arun K; Ray, Lalitagauri

    2011-07-01

    A bacterial strain, Bacillus cereus M(1)(16) (MTCC 5521), isolated and identified in our laboratory produces a green pigment when grown in nutrient broth at stationary condition. Optimum fermentation parameters for maximum pigment production are pH 7.0, temperature 30°C, time of incubation 72 h and inoculum volume 1% from 20 h grown cell suspension. Magnesium ion enhances pigment production whereas calcium and zinc ions inhibit the process. The pigment is better extracted from the fermented broth with chloroform in comparison with diethyl ether, ethyl acetate, and butanol. The extracted crude pigment consists of three fractions as revealed from thin layer chromatogram on silica gel GF254 using ethyl acetate and hexane (1:1) solvent system. The major fraction C(3) shows antibacterial activity against different gram positive bacteria. The proposed structure of C(3) is 9-methyl-1,4,5,8-tetra-azaphenanthrene obtained by elemental analysis, GC-MS, and NMR spectra studies.

  6. Development of ultrasensitive direct chemiluminescent enzyme immunoassay for determination of aflatoxin M1 in milk.

    Science.gov (United States)

    Vdovenko, Marina M; Lu, Chuan-Chen; Yu, Feng-Yih; Sakharov, Ivan Yu

    2014-09-01

    A direct competitive chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) for detecting aflatoxin M1 (AFM1) was developed. To improve the sensitivity of the assay, a mixture of 3-(10'-phenothiazinyl)-propane-1-sulfonate (SPTZ) and 4-morpholinopyridine (MORPH) was used to enhance peroxidase-induced CL. The concentrations of the coating anti-AFM1 antibody and the conjugate of AFB1 with horseradish peroxidase the conditions of the chemiluminescent assay were varied to optimise the condition of the chemiluminescent assay. The lower detection limit values and dynamic working range of CL-ELISA of AFM1 were 0.001 ng mL(-1) and 0.002-0.0075 ng mL(-1), respectively. A 20-fold dilution of milk samples prevented a matrix effect of the milk and allowed measurement of AFM1 at concentrations below than the maximum acceptable limit. Values of recovery within and between assays were 81.5-117.6% and 86-110.6%, respectively. The results of using the developed CL-ELISA to analyse samples of six brands of milk that were purchased in Taiwan revealed that AFM1 was absent from all studied samples.

  7. Enzyme-assisted extraction for the HPLC determination of aflatoxin M1 in cheese.

    Science.gov (United States)

    Pietri, Amedeo; Fortunati, Paola; Mulazzi, Annalisa; Bertuzzi, Terenzio

    2016-02-01

    The extraction of aflatoxin M1 (AFM1) from cheese is generally carried out using chlorinated organic solvents. In this study, two innovative methods were developed, based on an enzyme-assisted (EA) extraction using proteolytic enzymes (pepsin or pepsin-pancreatin). After purification through an immunoaffinity column, AFM1 is determined by HPLC-FLD. A comparison between the new EA methods and an established chloroform (CH) method was carried out on 24 cheese samples. The results showed that the extraction efficiency of the EA methods was independent of ripening time of cheese, whereas the CH method was not able to fully recover AFM1 from ripened cheeses. The simpler (pepsin) of the two methods has been adopted by our laboratory for routine analysis of AFM1 in cheese. In comparison with the CH method, the pepsin-HCl (P-HCl) method is simpler, avoiding solvent evaporation, dissolution and partition in a separating funnel; moreover, it gives higher recoveries, comparable LOD and LOQ and more accurate results.

  8. Cloning and Expression of Bile Salt Hydrolase Gene from Lactobacillus plantarum M1-UVS29

    Institute of Scientific and Technical Information of China (English)

    Yu Chang-qing; Li Rong

    2015-01-01

    We cloned and expressed bile salt hydrolase gene ofLactobacillus plantarum M1-UVS29 inLactococcus lactis NZ9000 successfully. Gene-specific primers for amplification ofL. plantarum bsh were designed by using sequence which availabled from GenBank. The production of PCR amplicon was confirmed by sequencing and cloned into pMD18-T vector, and then recombined into expression vector pNZ8148 and yielding vector pNZ8148-BSH. pNZ8148-BSH was transferred intoLactococcus lactis NZ9000. Sequencing indicated that the clonedbsh fragment contained 995 nucleotides, and shared 99.3% sequence homology withbsh gene fromL. plantarum MBUL10. Clonedbsh fragment was successfully transduced into NICE expression system and confirmed by PCR and restriction digest. Recombinant BSH protein was analyzed by SDS-PAGE. The molecular weight of BSH protein was approximately 37 ku. Activity of the expressed protein was 0.77 µmol• min-1. The successfully expressed proteins by genetic engineering technology made the function of lactic acid bacteria be abundant and laid the foundation for further researches into cholesterol-lowering lactic acid bacterium food and probiotics.

  9. Purification and characterization of virginiamycin M1 reductase from Streptomyces virginiae.

    Science.gov (United States)

    Suzuki, N; Lee, C K; Nihira, T; Yamada, Y

    1998-11-01

    Virginiamycin M1 (VM1), produced by Streptomyces virginiae, is a polyunsaturated macrocyclic lactone antibiotic belonging to the virginiamycin A group. S. virginiae possesses an activity which stereospecifically reduces a 16-carbonyl group of VM1, resulting in antibiotically inactive 16R-dihydroVM1. The corresponding VM1 reductase was purified to homogeneity from crude extracts of S. virginiae in five steps, with 5,650-fold purification and 23% overall yield. The N-terminal amino acid sequence was determined to be MAIKLVIA. The purified enzyme showed an apparent Mr of 73,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an Mr of 280,000 by native molecular sieve high-performance liquid chromatography, indicating the tetrameric nature of the native enzyme. NADPH served as a coenzyme for the reduction, with a Km value of 0.13 mM, but NADH did not support the reaction, even at a concentration of 5 mM, indicating the NADPH-specific nature of the enzyme. The Km for VM1 was determined to be 1.5 mM in the presence of 2 mM NADPH. In the reverse reaction, only 16R-dihydroVM1, not the 16S-epimer, served as a substrate, with a less than 0.1% overall reaction rate compared to that of the forward reaction, confirming that the VM1 reductase participates solely in VM1 inactivation in vivo.

  10. Monitoring of aflatoxin M1 in raw cow milk in Croatia during winter 2015

    Directory of Open Access Journals (Sweden)

    Nina Bilandžić

    2016-01-01

    Full Text Available A total of 548 raw milk samples were collected in the western, central and eastern regions of Croatia during February and March 2015. Aflatoxin M1 (AFM1 concentrations were quantified by the enzyme immunoassay method. The method limits of detection (LOD and quantification (LOQ were 22.2 and 34.2 ng/kg, respectively. The mean AFM1 levels measured in the three regions were (ng/kg as follows: western 3.69, central 3.11 and eastern 4.14. In total, the 548 samples analysed concentrations were below the LOD value and accordingly below the European Union maximum residue level (EU MRL of 50 ng/kg. The results suggest an absence of use of contaminated with aflatoxin B1 supplementary feedstuff for lactating cows in winter 2015. Such results might be related to the improved storage conditions for feed as well as to the enhanced and more stringent feed control system for mycotoxins in Croatia.

  11. [Cytogenetic investigations of bone marrow cells from mice exposed onboard biosatellite "Bion-M1"].

    Science.gov (United States)

    Dorozhkina, O V; Ivanov, A A

    2015-01-01

    The results of studying the mitotic activities and chromosomal aberrations in bone marrow cells from C57/BL6N mice with the help of the anaphase technique in 12 hours after completion of the 30-day "Bion-M1" mission and ground-based experiment using flight equipment are presented. A statistically reliable decline of the mitotic activity (0.74%) was found in cells taken from the space flown animals. In the ground-based experiment, a statistically reliable downward trend in proliferative activity (1.37%) was revealed after the comparison with groups of vivarium control (1.46-1.53%). In both experiments mice increased the number of initial mitotic phases (prophase + metaphase) relative to the sum of anaphases and telophases. The number of aberrant mitoses grew reliably in the group of flight animals by 29.7%, whereas in the ground-based experiment an upward trend was insignificant as their number increased up to 2.3% only. In the vivarium controls aberrant mitoses constituted 1.75-1.8%. An increase in chromosomal aberrations was largely due to such abnormalities as fragments. These findings seem to have been a result of summation of the effects of radiation and other stressful factors in space flight.

  12. THE M/M/1 QUEUE WITH WORKING VACATIONS AND VACATION INTERRUPTIONS

    Institute of Scientific and Technical Information of China (English)

    Jihong LI; Naishuo TIAN

    2007-01-01

    In this paper,we study the M/M/1 queue with working vacations and vacation interruptions.The working vacation is introduced recently,during which the server can still provide service on the original ongoing work at a lower rate.Meanwhile,we introduce a new policy:the server can come back from the vacation to the normal working level once some indices of the system,such as the number of customers,achieve a certain value in the vacation period.The server may come back from the vacation without completing the vacation.Such policy is called vacation interruption.We connect the above mentioned two policies and assume that if there are customers in the system after a service completion during the vacation period,the server will come back to the normal working level.In terms of the quasi birth and death process and matrix-geometric solution method,we obtain the distributions and the stochastic decomposition structures for the number of customers and the waiting time and provide some indices of systems.

  13. Seasonal patterns of aflatoxin M1 contamination in commercial pasteurised milk from different areas in Thailand.

    Science.gov (United States)

    Suriyasathaporn, Witaya; Nakprasert, Watinee

    2012-01-01

    Aflatoxin M1 (AFM1) levels were determined in pasteurised milk from five commercial trademarks produced in different areas in Thailand. One hundred and twenty milk samples were collected from local markets in Chiang Mai province, Thailand, to evaluate AFM1 concentrations using immunoaffinity columns and high-performance liquid chromatography with fluorescence detection. The overall median AFM1 level was 0.023 µg L(-1) ranging from 0.004 to 0.293 µg L(-1). All trademarks had average AFM1 concentrations lower than 0.05 µg L(-1), with those in Trademarks 3 to 5 being higher than Trademarks 1 and 2 (P < 0.01). All trademarks had different seasonal patterns of AFM1, even though operating in the same area. However, only Trademark 3 showed significant differences of AFM1 levels between seasons. The results suggested that farm management factors, rather than environment factors, were likely to be the main cause of AFM1 contamination in dairy products.

  14. Rapid and specific gray matter changes in M1 induced by balance training.

    Science.gov (United States)

    Taubert, Marco; Mehnert, Jan; Pleger, Burkhard; Villringer, Arno

    2016-06-01

    Training-induced changes in cortical structure can be observed non-invasively with magnetic resonance imaging (MRI). While macroscopic changes were found mainly after weeks to several months of training in humans, imaging of motor cortical networks in animals revealed rapid microstructural alterations after a few hours of training. We used MRI to test the hypothesis of immediate and specific training-induced alterations in motor cortical gray matter in humans. We found localized increases in motor cortical thickness after 1h of practice in a complex balancing task. These changes were specific to motor cortical effector representations primarily responsible for balance control in our task (lower limb and trunk) and these effects could be confirmed in a replication study. Cortical thickness changes (i) linearly increased across the training session, (ii) occurred independent of alterations in resting cerebral blood flow and (iii) were not triggered by repetitive use of the lower limbs. Our findings show that motor learning triggers rapid and specific gray matter changes in M1.

  15. Occurrence of aflatoxin M1 in raw milk of five dairy species in Ahvaz, Iran.

    Science.gov (United States)

    Rahimi, E; Bonyadian, M; Rafei, M; Kazemeini, H R

    2010-01-01

    During November 2007 to December 2008, 311 samples of raw milk from cow, water buffalo, camel, sheep, and goat were collected in the Ahvaz (southwest Iran). All of the samples were analyzed for presence of aflatoxin M1 (AFM1) by competitive ELISA technique. AFM1 was found in 42.1% of the samples by average concentration of 43.3+/-43.8 ng/kg. The incidence rates of AFM1 in raw cow, water buffalo, camel, sheep, and goat milks were, 78.7%, 38.7%, 12.5%, 37.3%, and 27.1%, respectively. The concentration of AFM1 in all of the samples were lower than Iranian national standard and FDA limit (500 ng/l), but in 36% of raw cow milk, 8% water buffalo milk, 3.9% sheep milk, and 5.7% raw goat milk samples were higher than maximum tolerance limit accepted by European union/Codex Alimentarius Commission (50 ng/l). The results showed that the milk of camel, goat, and sheep is safe respect to AFM1 contamination in this area.

  16. Repeatability of ellipsometric data in cholera toxin G M1-ELISA structures

    Science.gov (United States)

    Castro, Leon G.; Thompson, Daniel W.; Tiwald, Thomas; Berberov, Emil M.; Woollam, John A.

    2007-04-01

    The need for repeated measurements in a wide range of biological testing due to statistical variations is well known. In this paper, we discuss a specific example in which the measurement probe is a spectroscopic ellipsometer. Repeatable results are needed in a wide range of applications such as drug testing, immunoassays and other tests for disease, and fundamental biomaterial research. The present paper seeks to help reduce the non-meaningful causes of lack of repeatability by identifying a large number of externally controllable factors. Another goal of this work was to quantify the effects of many of these factors on ellipsometric measurements. By exploiting the sensitivity of spectroscopic ellipsometry to ultrathin layers, improved ways to detect and quantitatively differentiate biological events can be explored. This initial work was motivated from an interest to distinguish one disease from another or discern effects of one drug from another using the high surface sensitivity of spectroscopic ellipsometry. In this paper, we investigate the example biological system of cholera toxin (CT) in an ELISA structure with monosialoganglioside (G M1).

  17. Binding of aflatoxin M1 to different protein fractions in ovine and caprine milk.

    Science.gov (United States)

    Barbiroli, A; Bonomi, F; Benedetti, S; Mannino, S; Monti, L; Cattaneo, T; Iametti, S

    2007-02-01

    The affinity of aflatoxin M1 toward the main milk protein fractions in ewe and goat milk was investigated by using an ELISA. This study took into account the possible effects of common dairy processes such as ultrafiltration, acidic or rennet curding, and production of ricotta from acidic or rennet whey. Treatments that allowed the separation of casein from whey proteins under conditions that do not alter the physical or chemical status of the proteins (such as ultracentrifugation) were used as a reference. None of the treatments used in typical dairy processes caused significant release of the toxin, in spite of the relevant changes they induced in the interactions among proteins. Only the combined heat and acidic treatment used for production of ricotta cheese altered the structure of whey proteins to the point where they lost their ability to bind the toxin. This study also showed that, regardless of the physical state of the sample, a commercial electronic nose device, in combination with appropriate statistical tools, was able to discriminate among different levels of sample contamination.

  18. Nonlinear phase of the compressional m=1 diocotron instability: Saturation and analogy with geophysical fluid dynamics

    Science.gov (United States)

    Delzanno, G. L.; Finn, J. M.; Lapenta, G.

    2002-12-01

    The nonlinear dynamics of a Penning trap plasma, including the effect of the finite length and end curvature of the plasma column, is studied. A new cylindrical particle-in-cell code, called KANDINSKY, has been implemented by using a new interpolation scheme. The principal idea is to calculate the volume of each cell from a particle volume, in the same manner as is done for the cell charge. With this new method, the density is conserved along streamlines and artificial sources of compressibility are avoided. The code has been validated with a number of tests. The code is then used to compare the dynamics of three different models: the standard Euler or drift-Poisson model, the modified drift-Poisson model [J. Finn et al. Phys. Plasmas 6, 3744 (1999); Phys. Rev. Lett. 84, 2401 (2000)] with compressional effects, and the quasigeostrophic model of geophysical fluid dynamics in the limit of the γ-plane approximation. The results of this investigation show that Penning traps can be used to simulate geophysical fluids. Moreover, the results for the m=1 diocotron instability reproduce qualitatively the experiments [C. F. Driscoll, Phy. Rev. Lett. 64, 645 (1990); C. F. Driscoll et al. Phys. Fluids B 2, 1359 (1990)]: The instability turns the plasma "inside-out" resulting at the end in a stable, monotonic profile.

  19. Loss of Forkhead box M1 promotes erythropoiesis through increased proliferation of erythroid progenitors.

    Science.gov (United States)

    Youn, Minyoung; Wang, Nan; LaVasseur, Corinne; Bibikova, Elena; Kam, Sharon; Glader, Bertil; Sakamoto, Kathleen M; Narla, Anupama

    2017-05-01

    Forkhead box M1 (FOXM1) belongs to the forkhead/winged-helix family of transcription factors and regulates a network of proliferation-associated genes. Its abnormal upregulation has been shown to be a key driver of cancer progression and an initiating factor in oncogenesis. FOXM1 is also highly expressed in stem/progenitor cells and inhibits their differentiation, suggesting that FOXM1 plays a role in the maintenance of multipotency. However, the exact molecular mechanisms by which FOXM1 regulates human stem/progenitor cells are still uncharacterized. To understand the role of FOXM1 in normal hematopoiesis, human cord blood CD34(+) cells were transduced with FOXM1 short hairpin ribonucleic acid (shRNA) lentivirus. Knockdown of FOXM1 resulted in a 2-fold increase in erythroid cells compared to myeloid cells. Additionally, knockdown of FOXM1 increased bromodeoxyuridine (BrdU) incorporation in erythroid cells, suggesting greater proliferation of erythroid progenitors. We also observed that the defective phosphorylation of FOXM1 by checkpoint kinase 2 (CHK2) or cyclin-dependent kinases 1/2 (CDK1/2) increased the erythroid population in a manner similar to knockdown of FOXM1. Finally, we found that an inhibitor of FOXM1, forkhead domain inhibitor-6 (FDI-6), increased red blood cell numbers through increased proliferation of erythroid precursors. Overall, our data suggest a novel function of FOXM1 in normal human hematopoiesis. Copyright© Ferrata Storti Foundation.

  20. Detection of aflatoxin M1 in human breast milk and raw cow's milk in Istanbul, Turkey.

    Science.gov (United States)

    Keskin, Yaşar; Başkaya, Ruhtan; Karsli, Seher; Yurdun, Türkan; Ozyaral, Oğuz

    2009-04-01

    This survey was undertaken to determine the extent of aflatoxin M1 (AFM1) contamination in human breast milk and raw cow's milk in Istanbul, Turkey. Samples of human and raw cow's milk were collected randomly and analyzed for AFM1 using an enzyme-linked immunosorbent assay and high-performance liquid chromatography with fluorescence detection in which the samples were cleaned up with immunoaffinity columns. In this study, AFM, was detected in 8 (13.1%) of 61 human breast milk samples examined (mean +/- SD level, 5.68 +/- 0.62 ng/liter; range, 5.10 to 6.90 ng/liter) and 20 (33.3%) of 60 raw cow's milk samples examined (range, 5.40 to 300.20 ng/liter). Five (8.3%) of the positive raw cow's milk samples had AFM1 levels (153.52 +/- 100.60 ng/liter; range, 61.20 to 300.20 ng/liter) that were higher than the maximum tolerance limit (0.05 ppb) stipulated by regulations in Turkey and some other countries.

  1. Pancreatic Resections for Advanced M1-Pancreatic Carcinoma: The Value of Synchronous Metastasectomy

    Directory of Open Access Journals (Sweden)

    S. K. Seelig

    2010-01-01

    Materials and Methods. From January 1, 2004 to December, 2007 a total of 20 patients with pancreatic malignancies were retrospectively evaluated who underwent pancreatic surgery with synchronous resection of hepatic, adjacent organ, or peritoneal metastases for proven UICC stage IV periampullary cancer of the pancreas. Perioperative as well as clinicopathological parameters were evaluated. Results. There were 20 patients (9 men, 11 women; mean age 58 years identified. The primary tumor was located in the pancreatic head (n=9, 45%, in pancreatic tail (n=9, 45%, and in the papilla Vateri (n=2, 10%. Metastases were located in the liver (n=14, 70%, peritoneum (n=5, 25%, and omentum majus (n=2, 10%. Lymphnode metastases were present in 16 patients (80%. All patients received resection of their tumors together with metastasectomy. Pylorus preserving duodenopancreatectomy was performed in 8 patients, distal pancreatectomy in 8, duodenopancreatectomy in 2, and total pancreatectomy in 2. Morbidity was 45% and there was no perioperative mortality. Median postoperative survival was 10.7 months (2.6–37.7 months which was not significantly different from a matched-pair group of patients who underwent pancreatic resection for UICC adenocarcinoma of the pancreas (median survival 15.6 months; P=.1. Conclusion. Pancreatic resection for M1 periampullary cancer of the pancreas can be performed safely in well-selected patients. However, indication for surgery has to be made on an individual basis.

  2. First observation of the M1 transition $\\psi^\\prime\\to \\gamma\\eta_c^\\prime$

    CERN Document Server

    Ablikim, M; Ambrose, D J; An, F F; An, Q; An, Z H; Bai, J Z; Ban, Y; Becker, J; Berger, N; Bertani, M; Bian, J M; Boger, E; Bondarenko, O; Boyko, I; Briere, R A; Bytev, V; Cai, X; Calcaterra, A; Cao, G F; Chang, J F; Chelkov, G; Chen, G; Chen, H S; Chen, J C; Chen, M L; Chen, S J; Chen, Y; Chen, Y B; Cheng, H P; Chu, Y P; Cronin-Hennessy, D; Dai, H L; Dai, J P; Dedovich, D; Deng, Z Y; Denig, A; Denysenko, I; Destefanis, M; Ding, W M; Ding, Y; Dong, L Y; Dong, M Y; Du, S X; Fang, J; Fang, S S; Fava, L; Feldbauer, F; Feng, C Q; Ferroli, R B; Fu, C D; Fu, J L; Gao, Y; Geng, C; Goetzen, K; Gong, W X; Gradl, W; Greco, M; Gu, M H; Gu, Y T; Guan, Y H; Guo, A Q; Guo, L B; Guo, Y P; Han, Y L; Hao, X Q; Harris, F A; He, K L; He, M; He, Z Y; Held, T; Heng, Y K; Hou, Z L; Hu, H M; Hu, J F; Hu, T; Huang, B; Huang, G M; Huang, J S; Huang, X T; Huang, Y P; Hussain, T; Ji, C S; Ji, Q; Ji, X B; Ji, X L; Jia, L K; Jiang, L L; Jiang, X S; Jiao, J B; Jiao, Z; Jin, D P; Jin, S; Jing, F F; Kalantar-Nayestanaki, N; Kavatsyuk, M; Kuehn, W; Lai, W; Lange, J S; Leung, J K C; Li, C H; Li, Cheng; Li, Cui; Li, D M; Li, F; Li, G; Li, H B; Li, J C; Li, K; Li, Lei; Li, N B; Li, Q J; Li, S L; Li, W D; Li, W G; Li, X L; Li, X N; Li, X Q; Li, X R; Li, Z B; Liang, H; Liang, Y F; Liang, Y T; Liao, G R; Liao, X T; Liu, B J; Liu, B J; Liu, C L; Liu, C X; Liu, C Y; Liu, F H; Liu, Fang; Liu, Feng; Liu, H; Liu, H B; Liu, H H; Liu, H M; Liu, H W; Liu, J P; Liu, K Y; Liu, Kai; Liu, Kun; Liu, P L; Liu, S B; Liu, X; Liu, X H; Liu, Y; Liu, Y B; Liu, Z A; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H; Lu, G R; Lu, H J; Lu, J G; Lu, Q W; Lu, X R; Lu, Y P; Luo, C L; Luo, M X; Luo, T; Luo, X L; Lv, M; Ma, C L; Ma, F C; Ma, H L; Ma, Q M; Ma, S; Ma, T; Ma, X Y; Ma, Y; Maas, F E; Maggiora, M; Malik, Q A; Mao, H; Mao, Y J; Mao, Z P; Messchendorp, J G; Min, J; Min, T J; Mitchell, R E; Mo, X H; Morales, C Morales; Motzko, C; Muchnoi, N Yu; Nefedov, Y; Nicholson, C; Nikolaev, I B; Ning, Z; Olsen, S L; Ouyang, Q; Pacetti, S; Park, J W; Pelizaeus, M; Peng, H P; Peters, K; Ping, J L; Ping, R G; Poling, R; Prencipe, E; Pun, C S J; Qi, M; Qian, S; Qiao, C F; Qin, X S; Qin, Y; Qin, Z H; Qiu, J F; Rashid, K H; Rong, G; Ruan, X D; Sarantsev, A; Schaefer, B D; Schulze, J; Shao, M; Shen, C P; Shen, X Y; Sheng, H Y; Shepherd, M R; Song, X Y; Spataro, S; Spruck, B; Sun, D H; Sun, G X; Sun, J F; Sun, S S; Sun, X D; Sun, Y J; Sun, Y Z; Sun, Z J; Sun, Z T; Tang, C J; Tang, X; Thorndike, E H; Tian, H L; Toth, D; Ullrich, M; Varner, G S; Wang, B; Wang, B Q; Wang, K; Wang, L L; Wang, L S; Wang, M; Wang, P; Wang, P L; Wang, Q; Wang, Q J; Wang, S G; Wang, X F; Wang, X L; Wang, Y D; Wang, Y F; Wang, Y Q; Wang, Z; Wang, Z G; Wang, Z Y; Wei, D H; Weidenkaff, P; Wen, Q G; Wen, S P; Werner, M; Wiedner, U; Wu, L H; Wu, N; Wu, S X; Wu, W; Wu, Z; Xia, L G; Xiao, Z J; Xie, Y G; Xiu, Q L; Xu, G F; Xu, G M; Xu, H; Xu, Q J; Xu, X P; Xu, Y; Xu, Z R; Xue, F; Xue, Z; Yan, L; Yan, W B; Yan, Y H; Yang, H X; Yang, T; Yang, Y; Yang, Y X; Ye, H; Ye, M; Ye, M H; Yu, B X; Yu, C X; Yu, J S; Yu, L; Yu, S P; Yuan, C Z; Yuan, W L; Yuan, Y; Zafar, A A; Zallo, A; Zeng, Y; Zhang, B X; Zhang, B Y; Zhang, C C; Zhang, D H; Zhang, H H; Zhang, H Y; Zhang, J; Zhang, J G; Zhang, J Q; Zhang, J W; Zhang, J Y; Zhang, J Z; Zhang, L; Zhang, S H; Zhang, T R; Zhang, X J; Zhang, X Y; Zhang, Y; Zhang, Y H; Zhang, Y S; Zhang, Z P; Zhang, Z Y; Zhao, G; Zhao, H S; Zhao, J W; Zhao, K X; Zhao, Lei; Zhao, Ling; Zhao, M G; Zhao, Q; Zhao, S J; Zhao, T C; Zhao, X H; Zhao, Y B; Zhao, Z G; Zhemchugov, A; Zheng, B; Zheng, J P; Zheng, Y H; Zheng, Z P; Zhong, B; Zhong, J; Zhou, L; Zhou, X K; Zhou, X R; Zhu, C; Zhu, K; Zhu, K J; Zhu, S H; Zhu, X L; Zhu, X W; Zhu, Y M; Zhu, Y S; Zhu, Z A; Zhuang, J; Zou, B S; Zou, J H; Zuo, J X

    2012-01-01

    Using a sample of 106 million $\\psi^\\prime$ events collected with the BESIII detector at the BEPCII storage ring, we have made the first measurement of the M1 transition between the radially excited charmonium $S$-wave spin-triplet and the radially excited $S$-wave spin-singlet states: $\\psi^\\prime\\to\\gamma\\eta_c^\\prime$. Analyses of the processes $\\psi^\\prime\\to \\gamma\\eta_c^\\prime$ with $\\eta_c^\\prime\\to \\K_S^0 K\\pi$ and $K^+K^-\\pi^0$ gave an $\\eta_c^\\prime$ signal with a statistical significance of greater than 10 standard deviations under a wide range of assumptions about the signal and background properties. The data are used to obtain measurements of the $\\eta_c^\\prime$ mass ($M(\\eta_c^\\prime)=3637.6\\pm 2.9_\\mathrm{stat}\\pm 1.6_\\mathrm{sys}$ MeV/$c^2$), width ($\\Gamma(\\eta_c^\\prime)=16.9\\pm 6.4_\\mathrm{stat}\\pm 4.8_\\mathrm{sys}$ MeV), and the product branching fraction ($\\BR(\\psi^\\prime\\to \\gamma\\eta_c^\\prime)\\times \\BR(\\eta_c^\\prime\\to K\\bar K\\pi) = (1.30\\pm 0.20_\\mathrm{stat}\\pm 0.30_\\mathrm{sys})\\tim...

  3. The aflatoxin M1 crisis in the Serbian dairy sector: the year after.

    Science.gov (United States)

    Miocinovic, Jelena; Keskic, Tanja; Miloradovic, Zorana; Kos, Andrea; Tomasevic, Igor; Pudja, Predrag

    2017-03-01

    During the last 3 years, high aflatoxin M1 (AFM1) concentrations in milk and dairy products occurred in Serbia. It resulted in periodical change of the official regulations regarding maximum levels (MLs) of AFM1 as set by the Serbian Government. The aim of this study was to compare the occurrence of AFM1 in raw milk and dairy products during 2015 and also to determine whether there were some differences in AFM1 level among seasons. The AFM1 level exceeded the European Union ML in 29.3% of raw milk and 4.2% of milk product samples. The highest level of AFM1 in raw milk was found during the autumn season, while during the rest of the 2015, it was significantly lower. Although the improvement of dairy products safety was evident in 2015 when compared to 2013 and 2014, the cause of high concentrations in raw milk remained unresolved yet. This study indicates that dairy plants introduced control measures and refused reception of too high contaminated raw milk.

  4. Assessment of aflatoxin M1 in maternal breast milk in Eastern Turkey.

    Science.gov (United States)

    Atasever, Meryem; Yildirim, Yeliz; Atasever, Mustafa; Tastekin, Ayhan

    2014-04-01

    Breastfeeding may be considered as a risk factor for aflatoxin M1 (AFM1) exposure in early infancy. Hence, AFM1 levels in maternal breast milk (MBM) and the correlation between moldy cheese consumption of lactating mothers and infant exposure to AFM1 were investigated in this study. MBM samples from 73 lactating women randomly selected in hospitals located in Eastern Turkey were analysed for the presence of AFM1 using competitive ELISA. Out of 73 lactating mothers, 44 of them had the habit of cheese consumption (at least once a week), while remaining 29 had no such habit. AFM1 was detected in MBM of 18 out of 73 samples (24.6%); 12 MBM of 44 lactating mothers with moldy cheese consumption habit (27.2%) and 6 MBM of 29 mothers with no such habit (20.6%) with the range of 1.3-6.0 ng/l. None of the samples exceeded the limit set by EU and Turkish legislations. Moldy cheese consumption habit of lactating mothers exhibited no significant correlation with the presence of AFM1 in their milk (p>0.05). The results indicated that the relative risk of infant AFM1 exposure via MBM of moldy cheese consuming mother was not higher than MBM of mothers with no such habit.

  5. Medical students who decompress during the M-1 year outperform those who fail and repeat it: A study of M-1 students at the University of Illinois College of Medicine at Urbana-Champaign 1988–2000

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    Freund Gregory G

    2005-05-01

    Full Text Available Abstract Background All medical schools must counsel poor-performing students, address their problems and assist them in developing into competent physicians. The objective of this study was to determine whether students with academic deficiencies in their M-1 year graduate more often, spend less time to complete the curriculum, and need fewer attempts at passing USMLE Step 1 and Step 2 by entering the Decompressed Program prior to failure of the M-1 year than those students who fail the M-1 year and then repeat it. Method The authors reviewed the performance of M-1 students in the Decompressed Program and compared their outcomes to M-1 students who failed and fully repeated the M-1 year. To compare the groups upon admission, t-Tests comparing the Cognitive Index of students and MCAT scores from both groups were performed. Performance of the two groups after matriculation was also analyzed. Results Decompressed students were 2.1 times more likely to graduate. Decompressed students were 2.5 times more likely to pass USMLE Step 1 on the first attempt than the repeat students. In addition, 46% of those in the decompressed group completed the program in five years compared to 18% of the repeat group. Conclusion Medical students who decompress their M-1 year prior to M-1 year failure outperform those who fail their first year and then repeat it. These findings indicate the need for careful monitoring of M-1 student performance and early intervention and counseling of struggling students.

  6. Helicobacter pylori genotyping from positive clotests in patients with duodenal ulcer

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    Mattar Rejane

    2000-01-01

    Full Text Available Even though the seroprevalence of H. pylori may be high in the normal population, a minority develops peptic ulcer. Colonization of the gastric mucosa by more pathogenic vacA strains of H. pylori seems to be associated with enhanced gastric inflammation and duodenal ulcer. H. pylori genotyping from positive CLOtests was developed to determine the vacA genotypes and cagA status in 40 duodenal ulcer patients and for routine use. The pathogenic s1b/ m1/ cagA genotype was the most frequently occurring strain (17/42.5%; only two (5% patients presented the s2/ m2 genotype, the less virulent strain. Multiple strains were also detected in 17 (42.5% patients. Multiple strains of H. pylori colonizing the human stomach have been underestimated, because genotyping has been performed from cultures of H. pylori. We concluded that genotyping of H. pylori from a positive CLOtest had the advantages of reducing the number of biopsies taken during endoscopy, eliminating the step of culturing H. pylori, and assuring the presence of H. pylori in the specimen being processed.

  7. Progress in genotyping of Chlamydia trachomatis

    Institute of Scientific and Technical Information of China (English)

    Xia Yong; Xiong Likuan

    2014-01-01

    Objective To review the common genotyping techniques of Chlamydia trachomatis in terms of their principles,characteristics,applications and limitations.Data sources Data used in this review were mainly from English literatures of PubMed database.The search terms were "Chlamydia trachomatis" and "genotyping".Meanwhile,data from World Health Organization were also cited.Study selection Original articles and reviews relevant to present review's theme were selected.Results Different genotyping techniques were applied on different occasions according to their characteristics,especially in epidemiological studies worldwide,which pushed the study of Chlamydia trachomatis forward greatly.In addition,summaries of some epidemiological studies by genotyping were also included in this work for reference and comparison.Conclusions A clear understanding of common genotyping techniques could be helpful to genotype C.trachomatis more appropriately and effectively.Furthermore,more studies on the association of genotypes of Ch/amydia trachomatis with clinical manifestations should be performed.

  8. Changed gene expression in subjects with schizophrenia and low cortical muscarinic M1 receptors predicts disrupted upstream pathways interacting with that receptor.

    Science.gov (United States)

    Scarr, E; Udawela, M; Thomas, E A; Dean, B

    2016-11-01

    We tested the hypothesis that, compared with subjects with no history of psychiatric illness (controls), changes in gene expression in the dorsolateral prefrontal cortex from two subgroups of subjects with schizophrenia, one with a marked deficit in muscarinic M1 receptors (muscarinic receptor-deficit schizophrenia (MRDS)), would identify different biochemical pathways that would be affected by their aetiologies. Hence, we measured levels of cortical (Brodmann area 9) mRNA in 15 MRDS subjects, 15 subjects with schizophrenia but without a deficit in muscarinic M1 receptors (non-MRDS) and 15 controls using Affymetrix Exon 1.0 ST arrays. Levels of mRNA for 65 genes were significantly different in the cortex of subjects with MRDS and predicted changes in pathways involved in cellular movement and cell-to-cell signalling. Levels of mRNA for 45 genes were significantly different in non-MRDS and predicted changes in pathways involved in cellular growth and proliferation as well as cellular function and maintenance. Changes in gene expression also predicted effects on pathways involved in amino acid metabolism, molecular transport and small-molecule biochemistry in both MRDS and non-MRDS. Overall, our data argue a prominent role for glial function in MRDS and neurodevelopment in non-MRDS. Finally, the interactions of gene with altered levels of mRNA in the cortex of subjects with MRDS suggest many of their affects will be upstream of the muscarinic M1 receptor. Our study gives new insight into the molecular pathways affected in the cortex of subjects with MRDS and supports the notion that studying subgroups within the syndrome of schizophrenia is worthwhile.Molecular Psychiatry advance online publication, 1 November 2016; doi:10.1038/mp.2016.195.

  9. Cytosolic Pellino-1-Mediated K63-Linked Ubiquitination of IRF5 in M1 Macrophages Regulates Glucose Intolerance in Obesity

    Directory of Open Access Journals (Sweden)

    Donghyun Kim

    2017-07-01

    Full Text Available IRF5 is a signature transcription factor that induces M1 macrophage polarization. However, little is known regarding cytosolic proteins that induce IRF5 activation for M1 polarization. Here, we report the interaction between ubiquitin E3 ligase Pellino-1 and IRF5 in the cytoplasm, which increased nuclear translocation of IRF5 by K63-linked ubiquitination in human and mouse M1 macrophages. LPS and/or IFN-γ increased Pellino-1 expression, and M1 polarization was attenuated in Pellino-1-deficient macrophages in vitro and in vivo. Defective M1 polarization in Pellino-1-deficient macrophages improved glucose intolerance in mice fed a high-fat diet. Furthermore, macrophages in adipose tissues from obese humans exhibited increased Pellino-1 expression and IRF5 nuclear translocation compared with nonobese subjects, and these changes are associated with insulin resistance index. This study demonstrates that cytosolic Pellino-1-mediated K63-linked ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in obesity, suggesting a cytosolic mediator function of Pellino-1 in TLR4/IFN-γ receptor-IRF5 axis during M1 polarization.

  10. Inhibition of M1 macrophage activation in adipose tissue by berberine improves insulin resistance.

    Science.gov (United States)

    Ye, Lifang; Liang, Shu; Guo, Chao; Yu, Xizhong; Zhao, Juan; Zhang, Hao; Shang, Wenbin

    2016-12-01

    Insulin resistance is associated with a chronic inflammation in adipose tissue which is propagated by a phenotypic switch in adipose tissue macrophage (ATM) polarization. This study aimed to investigate whether berberine, the major alkaloid of rhizoma coptidis, can improve insulin resistance through inhibiting ATM activation and inflammatory response in adipose tissue. High-fat-diet induced obese mice were administered oral with berberine (50mg/kg/day) for 14days. ATMs were analysed using FACS and insulin resistance was evaluated. Expressions of pro-inflammatory cytokines and activation of inflammatory pathways were detected. The chemotaxis of macrophages was measured. Glucose consumption and insulin signalling of adipocytes were examined. Berberine significantly decreased F4/80(+)/CD11c(+)/CD206(-) cells in the stromal vascular fraction from adipose tissue and improved glucose tolerance in obsess mice. In addition, berberine reduced the elevated levels of serum TNF-α, IL-6 and MCP-1 and the expressions of TNF-α, IL-6 and MCP-1 and attenuated the phosphorylation of JNK and IKKβ and the expression of NF-κB p65 in the obese adipose tissue, Raw264.7 macrophages and 3T3-L1 adipocytes, respectively. The phosphorylation of IRS-1 (Ser307) was inhibited by berberine in adipose tissue and cultured adipocytes. The phosphorylation of AKT (Ser473) was increased in berberine-treated adipose tissue. Conditioned medium from adipocytes treated with berberine reduced the number of infiltrated macrophages. Berberine partly restored the impaired glucose consumption and the activation of IRS-1 (Ser307) in adipocytes induced by the activation of macrophages. Our findings imply that berberine improves insulin resistance by inhibiting M1 macrophage activation in adipose tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Transport of Aflatoxin M1 in human intestinal Caco-2/TC7 cells

    Directory of Open Access Journals (Sweden)

    Francesca eCaloni

    2012-06-01

    Full Text Available Aflatoxin M1 (AFM1 is a hydroxylated metabolite of aflatoxin B1 (AFB1. After it is formed, it is secreted in the milk of mammals.Despite the potential risk of human exposure to AFM1, data reported in literature on the metabolism, toxicity and bioavailability of this molecule are limited and out of date. The aim of the present research was to study the absorption profile of AFM1 and possible damage to tight junctions of the intestinal Caco-2/TC7 clone grown on microporous filter supports. These inserts allowed for the separation of the apical and basolateral compartments which correspond to the in vivo lumen and the interstitial space/vascular systems of intestinal mucosa respectively.In this study, the Caco-2/TC7 cells were treated with different AFM1 concentrations (10-10,000 ng/kg for short (40 minutes and long periods of time (48 hours. The AFM1 influx/efflux transport and effects on tight junctions were evaluated by measuring trans-epithelial electrical resistance and observing tight junction protein (Zonula occludens-1 and occludin localization.The results showed that: i when introduced to the apical and basolateral compartments, AFM1 was poorly absorbed by the Caco-2/TC7 cells but its transport across the cell monolayer occurred very quickly (Papp value of 105.10 ± 7.98 cm/s x 10-6. ii The integrity of tight junctions was not permanently compromised after exposure to the mycotoxin. Viability impairment or barrier damage did not occur either.The present results contribute to the evaluation of human risk exposure to AFM1, although the AFM1 transport mechanism need to be clarified.

  12. NST and IRIS multi-wavelength observations of an M1.0 class solar flare

    Science.gov (United States)

    Vargas Domínguez, Santiago; Sadykov, Viacheslav; Kosovichev, Alexander; Sharykin, Ivan; Struminsky, Alexei; Zimovets, Ivan

    2015-08-01

    Although solar flares are the most energetic events in the Solar System and have direct impact in the interplanetary space and ultimately in our planet, there are still many unresolved issues concerning their generation, the underlying processes of particle acceleration involved, the effect at different layer in the solar atmosphere, among others. This work presents new coordinated observations from the New Solar Telescope (NST) and the space telescope IRIS that acquired simultaneous observations of an M1.0 class flare occurred on 12 June, 2014 in active region NOAA 12087. NST filtergrams using the TiO filter, together with chromospheric data from the Halpha line allow us to study the evolution of the event from the first signs of the intensification of the intensity in the region. We focused on a small portion where the intensity enhancement in Halpha (blue and red wings) seems to be triggered, and discovered a rapid expansion of a flux-rope structure near the magnetic neutral line, in the sequence of high-resolution photospheric images. IRIS observations evidenced strong emission of the chromospheric and transition region lines during the flare. Jet-like structures are detected before the initiation of the flare in chromospheric lines and strong non-thermal emission in the transition region at the beginning of the impulsive phase. Evaporation flows with velocities up to 50 km/s occurred in the hot chromospheric plasma. We interpreted the result in terms of the “gentle” evaporation that occurs after accelerated particles heat the chromosphere.

  13. Aflatoxin M1 contamination of human breast milk in Isfahan, Iran

    Science.gov (United States)

    Jafarian-Dehkordi, Abbas; Pourradi, Nasibeh

    2013-01-01

    Background: During the last decades there has been great attention paid to aflatoxins. They are highly toxic, immunosuppressive, mutagenic, teratogenic, and carcinogenic compounds. Aflatoxin M1 (AFM1), a hydroxylated metabolite of aflatoxin B1 (AFB1), is formed in the liver and excreted into the breast milk. It is considered to cause certain hygienic risks for infant health. The aim of this study was to evaluate the presence of the AFM1 in the breast milk using AFM1 in milk as a biomarker for exposure to aflatoxin B1 and determine the level of AFM1 contamination in the lactating mothers in Isfahan, Iran. Materials and Methods: This study was carried out on 80 lactating women randomly selected from two urban health centers. Mother's milk samples and information on food intake were collected from the participants using structured food-frequency questionnaire. Breast milk samples were tested for AFM1 by a competitive ELISA technique. Results: Our findings showed that only one sample was contaminated with AFM1 with concentrations of 6.8 ng/L. However, the AFM1 level in this sample was lower than the maximum tolerable limit (25 ng/L) accepted by the European Communities and Codex Alimentarius. Conclusion: Although the concentration of AFM1 in none of the samples was higher than the acceptable level, the presence of AFM1 in only one of them confirms the need for developing strategies to reduce exposure to aflatoxin in foods and to carry out biological monitoring of aflatoxins as a food quality control measure routinely. PMID:24524032

  14. Deletion of Forkhead Box M1 transcription factor from respiratory epithelial cells inhibits pulmonary tumorigenesis.

    Directory of Open Access Journals (Sweden)

    I-Ching Wang

    Full Text Available The Forkhead Box m1 (Foxm1 protein is induced in a majority of human non-small cell lung cancers and its expression is associated with poor prognosis. However, specific requirements for the Foxm1 in each cell type of the cancer lesion remain unknown. The present study provides the first genetic evidence that the Foxm1 expression in respiratory epithelial cells is essential for lung tumorigenesis. Using transgenic mice, we demonstrated that conditional deletion of Foxm1 from lung epithelial cells (epFoxm1(-/- mice prior to tumor initiation caused a striking reduction in the number and size of lung tumors, induced by either urethane or 3-methylcholanthrene (MCA/butylated hydroxytoluene (BHT. Decreased lung tumorigenesis in epFoxm1(-/- mice was associated with diminished proliferation of tumor cells and reduced expression of Topoisomerase-2alpha (TOPO-2alpha, a critical regulator of tumor cell proliferation. Depletion of Foxm1 mRNA in cultured lung adenocarcinoma cells significantly decreased TOPO-2alpha mRNA and protein levels. Moreover, Foxm1 directly bound to and induced transcription of the mouse TOPO-2alpha promoter region, indicating that TOPO-2alpha is a direct target of Foxm1 in lung tumor cells. Finally, we demonstrated that a conditional deletion of Foxm1 in pre-existing lung tumors dramatically reduced tumor growth in the lung. Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2alpha expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy.

  15. BION-M 1: First continuous blood pressure monitoring in mice during a 30-day spaceflight

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Popova, Anfisa; Lloret, Jean-Christophe; Aubry, Patrick; Borovik, Anatoliy; Tsvirkun, Daria; Vinogradova, Olga; Ilyin, Eugeniy; Gauquelin-Koch, Guillemette; Gharib, Claude; Custaud, Marc-Antoine

    2017-05-01

    Animals are an essential component of space exploration and have been used to demonstrate that weightlessness does not disrupt essential physiological functions. They can also contribute to space research as models of weightlessness-induced changes in humans. Animal research was an integral component of the 30-day automated Russian biosatellite Bion-M 1 space mission. The aim of the hemodynamic experiment was to estimate cardiovascular function in mice, a species roughly 3000 times smaller than humans, during prolonged spaceflight and post-flight recovery, particularly, to investigate if mice display signs of cardiovascular deconditioning. For the first time, heart rate (HR) and blood pressure (BP) were continuously monitored using implantable telemetry during spaceflight and recovery. Decreased HR and unchanged BP were observed during launch, whereas both HR and BP dropped dramatically during descent. During spaceflight, BP did not change from pre-flight values. However, HR increased, particularly during periods of activity. HR remained elevated after spaceflight and was accompanied by increased levels of exercise-induced tachycardia. Loss of three of the five mice during the flight as a result of the hardware malfunction (unrelated to the telemetry system) and thus the limited sample number constitute the major limitation of the study. For the first time BP and HR were continuously monitored in mice during the 30-day spaceflight and 7-days of post-flight recovery. Cardiovascular deconditioning in these tiny quadruped mammals was reminiscent of that in humans. Therefore, the loss of hydrostatic pressure in space, which is thought to be the initiating event for human cardiovascular adaptation in microgravity, might be of less importance than other physiological mechanisms. Further experiments with larger number of mice are needed to confirm these findings.

  16. Aflatoxin B1 and M1 Degradation by Lac2 from Pleurotus pulmonarius and Redox Mediators

    Science.gov (United States)

    Loi, Martina; Fanelli, Francesca; Zucca, Paolo; Liuzzi, Vania C.; Quintieri, Laura; Cimmarusti, Maria T.; Monaci, Linda; Haidukowski, Miriam; Logrieco, Antonio F.; Sanjust, Enrico; Mulè, Giuseppina

    2016-01-01

    Laccases (LCs) are multicopper oxidases that find application as versatile biocatalysts for the green bioremediation of environmental pollutants and xenobiotics. In this study we elucidate the degrading activity of Lac2 pure enzyme form Pleurotus pulmonarius towards aflatoxin B1 (AFB1) and M1 (AFM1). LC enzyme was purified using three chromatographic steps and identified as Lac2 through zymogram and LC-MS/MS. The degradation assays were performed in vitro at 25 °C for 72 h in buffer solution. AFB1 degradation by Lac2 direct oxidation was 23%. Toxin degradation was also investigated in the presence of three redox mediators, (2,2′-azino-bis-[3-ethylbenzothiazoline-6-sulfonic acid]) (ABTS) and two naturally-occurring phenols, acetosyringone (AS) and syringaldehyde (SA). The direct effect of the enzyme and the mediated action of Lac2 with redox mediators univocally proved the correlation between Lac2 activity and aflatoxins degradation. The degradation of AFB1 was enhanced by the addition of all mediators at 10 mM, with AS being the most effective (90% of degradation). AFM1 was completely degraded by Lac2 with all mediators at 10 mM. The novelty of this study relies on the identification of a pure enzyme as capable of degrading AFB1 and, for the first time, AFM1, and on the evidence that the mechanism of an effective degradation occurs via the mediation of natural phenolic compounds. These results opened new perspective for Lac2 application in the food and feed supply chains as a biotransforming agent of AFB1 and AFM1. PMID:27563923

  17. Testing GxG interactions between coinfecting microbial parasite genotypes within hosts

    Directory of Open Access Journals (Sweden)

    Rebecca D Schulte

    2014-05-01

    Full Text Available Host-parasite interactions represent one of the strongest selection pressures in nature. They are often governed by genotype-specific (GxG interactions resulting in host genotypes that differ in resistance and parasite genotypes that differ in virulence depending on the antagonist’s genotype. Another type of GxG interactions, which is often neglected but which certainly influences host-parasite interactions, are those between coinfecting parasite genotypes. Mechanistically, within-host parasite interactions may range from competition for limited host resources to cooperation for more efficient host exploitation. The exact type of interaction, i.e. whether competitive or cooperative, is known to affect life-history traits such as virulence. However, the latter has been shown for chosen genotype combinations only, not considering whether the specific genotype combination per se may influence the interaction (i.e. GxG interactions. Here, we want to test for the presence of GxG interactions between coinfections of the bacterium Bacillus thuringiensis infecting the nematode Caenorhabditis elegans by combining two non-pathogenic and five pathogenic strains in all possible ways. Furthermore, we evaluate whether the type of interaction, reflected by the direction of virulence change of multiple compared to single infections, is genotype-specific. Generally, we found no indication for GxG interactions between non-pathogenic and pathogenic bacterial strains, indicating that virulence of pathogenic strains is equally affected by both non-pathogenic strains. Specific genotype combinations, however, differ in the strength of virulence change, indicating that the interaction type between coinfecting parasite strains and thus the virulence mechanism is specific for different genotype combinations. Such interactions are expected to influence host-parasite interactions and to have strong implications for coevolution.

  18. Disturbed mitochondrial function restricts glutamate uptake in the human Müller glia cell line, MIO-M1

    DEFF Research Database (Denmark)

    Vohra, Rupali; Gurubaran, Iswariyaraja Sridevi; Henriksen, Ulrik Birk

    2017-01-01

    Using the human Müller cell line, MIO-M1, the aim was to study the impact of mitochondrial inhibition in Müller glia through antimycin A treatment. MIO-M1 cell survival, levels of released lactate, mitochondrial function, and glutamate uptake were studied in response to mitochondrial inhibition...... inhibition caused impaired glutamate uptake and decreased mRNA expression of the glutamate transporter, EAAT1. Over all, we show important roles of mitochondrial activity in MIO-M1 cell function and survival....

  19. Myeloid-specific Rictor deletion induces M1 macrophage polarization and potentiates in vivo pro-inflammatory response to lipopolysaccharide.

    Directory of Open Access Journals (Sweden)

    William T Festuccia

    Full Text Available The phosphoinositide-3-kinase (PI3K/protein kinase B (Akt axis plays a central role in attenuating inflammation upon macrophage stimulation with toll-like receptor (TLR ligands. The mechanistic target of rapamycin complex 2 (mTORC2 relays signal from PI3K to Akt but its role in modulating inflammation in vivo has never been investigated. To evaluate the role of mTORC2 in the regulation of inflammation in vivo, we have generated a mouse model lacking Rictor, an essential mTORC2 component, in myeloid cells. Primary macrophages isolated from myeloid-specific Rictor null mice exhibited an exaggerated response to TLRs ligands, and expressed high levels of M1 genes and lower levels of M2 markers. To determine whether the loss of Rictor similarly affected inflammation in vivo, mice were either fed a high fat diet, a situation promoting chronic but low-grade inflammation, or were injected with lipopolysaccharide (LPS, which mimics an acute, severe septic inflammatory condition. Although high fat feeding contributed to promote obesity, inflammation, macrophage infiltration in adipose tissue and systemic insulin resistance, we did not observe a significant impact of Rictor loss on these parameters. However, mice lacking Rictor exhibited a higher sensitivity to septic shock when injected with LPS. Altogether, these results indicate that mTORC2 is a key negative regulator of macrophages TLR signalling and that its role in modulating inflammation is particularly important in the context of severe inflammatory challenges. These observations suggest that approaches aimed at modulating mTORC2 activity may represent a possible therapeutic approach for diseases linked to excessive inflammation.

  20. Genotype by sex and genotype by age interactions with sedentary behavior: the Portuguese Healthy Family Study.

    Directory of Open Access Journals (Sweden)

    Daniel M V Santos

    Full Text Available Sedentary behavior (SB expression and its underlying causal factors have been progressively studied, as it is a major determinant of decreased health quality. In the present study we applied Genotype x Age (GxAge and Genotype x Sex (GxSex interaction methods to determine if the phenotypic expression of different SB traits is influenced by an interaction between genetic architecture and both age and sex. A total of 1345 subjects, comprising 249 fathers, 327 mothers, 334 sons and 325 daughters, from 339 families of The Portuguese Healthy Family Study were included in the analysis. SB traits were assessed by means of a 3-d physical activity recall, the Baecke and IPAQ questionnaires. GxAge and GxSex interactions were analyzed using SOLAR 4.0 software. Sedentary behaviour heritability estimates were not always statistically significant (p>0.05 and ranged from 3% to 27%. The GxSex and GxAge interaction models were significantly better than the single polygenic models for TV (min/day, EEsed (kcal/day, personal computer (PC usage and physical activty (PA tertiles. The GxAge model is also significantly better than the polygenic model for Sed (min/day. For EEsed, PA tertiles, PC and Sed, the GxAge interaction was significant because the genetic correlation between SB environments was significantly different from 1. Further, PC and Sed variance heterogeneity among distinct ages were observed. The GxSex interaction was significant for EEsed due to genetic variance heterogeneity between genders and for PC due to a genetic correlation less than 1 across both sexes. Our results suggest that SB expression may be influenced by the interactions between genotype with both sex and age. Further, different sedentary behaviors seem to have distinct genetic architectures and are differentially affected by age and sex.

  1. Evidence of a M1-muscarinic GPCR homolog in unicellular eukaryotes: featuring Acanthamoeba spp bioinformatics 3D-modelling and experimentations.

    Science.gov (United States)

    Baig, Abdul Mannan; Ahmad, H R

    2017-06-01

    Acetylcholine affects the target cellular function via muscarinic and nicotinic cholinergic receptors that are seen to exist in humans. Both the cholinergic receptors are G-protein coupled receptors (GPCRs) that perform cardinal functions in humans. Anti-muscarinic drugs, particularly the ones that target M1 subtype (mAChR1), have consistently shown to kill unicellular pathogenic eukaryotes like Acanthamoeba spp. As the M1 receptor subtype has not been reported to be expressed in the above protist, the presence of an ancient form of the M1 muscarinic receptor was inferred. Bioinformatic tools and experimental assays were performed to establish the presence of a ligand-binding site. A search for sequence homology of amino acids of human M1 receptor failed to uncover an equivalent ligand-binding site on Acanthamoeba, but structural bioinformatics showed a hypothetical protein L8HIA6 to be a receptor homolog of the human mAChR1. Immunostaining with an anti-mAChR1 antibody showed cellular staining. Growth assays showed proliferation and lethal effects of exposure to mAChR1 agonist and antagonist respectively. With the recent authentication of human mAChR1 structure and its addition to the database, it was possible to discover its structural analog in Acanthamoeba; which could explain the effects of anticholinergics observed in the past on Acanthamoeba spp. The discovery of a receptor homolog of human mAChR1 on Acanthamoeba with future studies planned to show its expression and binding to cholinergic agonist and antagonist would help clarify its role in the biology of this protist pathogen.

  2. Competitive ability of black common bean genotypes with weeds

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    Gilcimar Adriano Vogt

    2013-10-01

    Full Text Available The morpho-physiologic characteristics of common bean plants can affect their competitive ability with weeds. The objective of this work was to evaluate the competitive ability of black bean genotypes with weeds. An experiment was carried out in the 2010/11 cropping season in Papanduva, SC, southern Brazil, in order to verify the variability of some plant characteristics among genotypes of common bean. The randomized block design was used, with four replications. Seven cultivars underwent the treatments: BRS Campeiro, CHP 01-238, CHP 01-239, Diamante Negro, BRS Supremo, BRS Valente, IPR Uirapuru, FTS Soberano, IPR Graúna, IPR Tiziu e IAC Diplomata. At 6, 14, 18, 25 and 32 days after emergence (DAE were evaluated plant height, ground cover by common bean plants, dry biomass of stems and leaves, and grain yield. In the 2011/12 cropping season the same cultivars were grown in the presence or absence of weeds, adopting similar methodology to the 2010/11. The losses of grain yield in black common bean genotypes due to weed interference ranged from 30.8% to 54.9%. There was a positive correlation between yield reduction promoted by the weed infestation and dry biomass produced by the weeds. In addition, there was a positive correlation between percentage of yield reduction due to the weed infestation and grain yield without weed interference. The characteristics evaluated did not estimate the competitive ability of black common bean genotypes with weeds.

  3. Potential antioxidant response to coffee — A matter of genotype?

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    Ute Hassmann

    2014-12-01

    Full Text Available In a human intervention study, coffee combining natural green coffee bean constituents and dark roast products was identified as a genotype-dependent inducer of the Nrf2/ARE pathway, significantly affecting Nrf2 gene expression and downstream GST1A1 and UGT1A1 gene transcription. The observed transcriptional changes correlated with the presence of specific Nrf2 genotypes suggesting their influence on both Nrf2 and subsequent ARE-dependent GST1A1 and UGT1A1 transcription. While the presence of the −653 SNP seems to be advantageous, resulting in higher Nrf2, GST1A1 and UGT1A1 gene transcription following coffee consumption, in contrast, the presence of the −651 SNP significantly down-regulated the response to the study coffee. Furthermore, the presence of the B/B genotype in GST1A1 along with the frequency of the [TA]6/6 and [TA]7/7 polymorphisms in UGT1A1 appeared to significantly increase sensitivity toward coffee-induced gene transcription. This data suggests that when examining the role of the Nrf2/ARE pathway in the regulation of antioxidative and chemopreventive phase II efficacy, individual genotypes should be included when considering the potency of bioactive food/food constituents and their therapeutic potential.

  4. ACE Gene DD Genotype Association with Obesity in Pakistani Population

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    Amara Javaid

    2011-05-01

    Full Text Available The renin-angiotensin system (RAS has an established role in pathogenesis of metabolic etiologies. Angiotensin converting enzyme (ACE is an important component of RAS that may influence metabolic outcomes in adipose tissue. The deletion “D allele”, of ACE gene I/D (insertion/deletion polymorphism has been shown to be associated with rise in the serum level of ACE. This study is designed to correlate the association between ACE gene I/D polymorphism and obesity in adult population of Pakistan. Our study included 535 individuals; 147 normal with body mass index (BMI 19-24.9, 183 overweight (BMI 26-29.9 and 205 obese (BMI > 30. The individuals were genotyped for ACE gene I/D polymorphism. The ratio of ACE gene II and ID genotypes were not significantly different among normal, overweight and obese individuals. However, the DD genotype in normal, overweight and obese individuals was 12.9%, 18.0% and 28.8% respectively. DD genotype is significantly high (P = 0.002 in obese than in overweight and normal individuals. Thus the results of this study may suggest a possible association of the D allele in adipogenesis and adipocyte metabolism by affecting the ACE plasma level.

  5. Morphological and physiological characterization of different genotypes of faba bean under heat stress

    Science.gov (United States)

    Siddiqui, Manzer H.; Al-Khaishany, Mutahhar Y.; Al-Qutami, Mohammed A.; Al-Whaibi, Mohamed H.; Grover, Anil; Ali, Hayssam M.; Al-Wahibi, Mona Suliman

    2015-01-01

    Heat stress (HS) is the major constraint to crop productivity worldwide. The objective of the present experiment was to select the tolerant and sensitive genotype(s) on the basis of morpho-physiological and biochemical characteristics of ten Vicia faba genotypes. These genotypes were as follows: Zafar 1, Zafar 2, Shebam 1, Makamora, Espan, Giza Blanka, Giza 3, C4, C5 and G853. The experimental work was undertaken to study the effects of different levels of temperature (control, mild, and modest) on plant height (PH) plant−1, fresh weight (FW) and dry weight (DW) plant−1, area leaf−1, content of leaf relative water (RWC), proline content (Pro) and total chlorophyll (Total Chl), electrolyte leakage (EL), malondialdehyde level (MDA), hydrogen peroxide (H2O2), and activities of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) enzymes. HS significantly affected growth performance of all genotypes. However, the magnitude of reduction in genotypes ‘C5’ was relatively low, possibly due to its better antioxidant activities (CAT, POD and SOD), and accumulation of Pro and Total Chl, and leaf RWC. In the study, ‘C5’ was noted to be the most HS tolerant and ‘Espan’ most HS sensitive genotypes. It was concluded that the heat-tolerant genotypes may have better osmotic adjustment and protection from free radicals by increasing the accumulation of Pro content with increased activities of antioxidant enzyme. PMID:26288573

  6. Assessing the effects of ambient ozone in China on snap bean genotypes by using ethylenediurea (EDU).

    Science.gov (United States)

    Yuan, Xiangyang; Calatayud, Vicent; Jiang, Lijun; Manning, William J; Hayes, Felicity; Tian, Yuan; Feng, Zhaozhong

    2015-10-01

    Four genotypes of snap bean (Phaseolus vulgaris L.) were selected to study the effects of ambient ozone concentration at a cropland area around Beijing by using 450 ppm of ethylenediurea (EDU) as a chemical protectant. During the growing season, the 8h (9:00-17:00) average ozone concentration was very high, approximately 71.3 ppb, and AOT40 was 29.0 ppm.h. All genotypes showed foliar injury, but ozone-sensitive genotypes exhibited much more injury than ozone-tolerant ones. Compared with control, EDU significantly alleviated foliar injury, increased photosynthesis rate and chlorophyll a fluorescence, Vcmax and Jmax, and seed and pod weights in ozone-sensitive genotypes but not in ozone-tolerant genotypes. EDU did not significantly affect antioxidant contents in any of the genotypes. Therefore, EDU effectively protected sensitive genotypes from ambient ozone damage, while protection on ozone-tolerant genotypes was limited. EDU can be regarded as a useful tool in risk assessment of ambient ozone on food security.

  7. Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk.

    Science.gov (United States)

    Joseph, Michael A; Moysich, Kirsten B; Freudenheim, Jo L; Shields, Peter G; Bowman, Elise D; Zhang, Yueshang; Marshall, James R; Ambrosone, Christine B

    2004-01-01

    Cruciferous vegetables contain anticarcinogenic isothiocyanates (ITCs), particularly the potent sulforaphane, which may decrease risk of prostate cancer through induction of phase II enzymes, including glutathione S-transferases (GSTs). We evaluated this hypothesis in a population-based, case-control study of prostate cancer, including 428 men with incident prostate cancer and 537 community controls. An in-person interview included an extensive food-frequency questionnaire. Genotyping for deletions in GSTM1 and GSTT1 was performed in a subset of men who provided blood. Intakes of cruciferous vegetables and of broccoli, the greatest source of sulforaphane, were associated with decreased prostate cancer risk at all levels above the lowest consumers [adjusted 4th quartile odds ratio (OR)=0.58; 95% confidence interval (CI)=0.38, 0.89, and 0.72 (95% CI=0.49, 1.06)], respectively. In relation to genotypes, there was a nonsignificant increase in risk with the GSTT1 null genotype (OR=1.51; 95% CI=0.98, 2.31) but no effects of GSTM1 genotype. However, men with GSTM1-present genotype and high broccoli intake had the greatest reduction in risk (OR=0.49; 95% CI=0.27, 0.89). Our findings provide evidence that two or more servings per month of cruciferous vegetables may reduce risk of prostate cancer, especially among men with GSTM1-present alleles, and are consistent with a role of dietary ITCs as chemopreventive agents against prostate cancer.

  8. Tracklines of Multichannel Seismics Survey Collected During USGS Cruise M1-98-GM (GOM98LINE.SHP)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Shapefile showing tracklines of Multichannel Seismics Survey Collected During USGS Cruise M1-98-GM. This cruise was to the Mississippi Canyon region of the Gulf of...

  9. Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M1 exhibits improved potency against MRSA.

    Science.gov (United States)

    Hoang, N H; Huong, N L; Shrestha, A; Sohng, J K; Yoon, Y J; Park, J W

    2013-11-01

    A newly reduced macrocyclic lactone antibiotic streptogramin A, 5,6-dihydrovirginiamycin M1 was created by feeding virginiamycin M1 into a culture of recombinant Streptomyces venezuelae. Its chemical structure was spectroscopically elucidated, and this streptogramin A analogue showed twofold higher antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) compared with its parent molecule virginiamycin M1. Docking studies using the model of streptogramin A acetyltransferase (VatA) suggested that the newly generated analogue binds tighter with overall lower free energy compared with the parent molecule virginiamycin M1. This hypothesis was validated experimentally through the improvement of efficacy of the new analogue against MRSA strains. The biotransformation approach presented herein could have a broad application in the production of reduced macrocyclic molecules.

  10. Complete genome sequence of Streptococcus pyogenes M1 476, isolated from a patient with streptococcal toxic shock syndrome.

    Science.gov (United States)

    Miyoshi-Akiyama, Tohru; Watanabe, Shinya; Kirikae, Teruo

    2012-10-01

    Here, we report the completely annotated genome sequence of Streptococcus pyogenes M1 476 isolated from a patient with streptococcal toxic shock syndrome (STSS) during pregnancy. The genome sequence will provide new insights into the mechanisms underlying STSS.

  11. Complete Genome Sequence of Streptococcus pyogenes M1 476, Isolated from a Patient with Streptococcal Toxic Shock Syndrome

    OpenAIRE

    Miyoshi-Akiyama, Tohru; WATANABE, Shinya; Kirikae, Teruo

    2012-01-01

    Here, we report the completely annotated genome sequence of Streptococcus pyogenes M1 476 isolated from a patient with streptococcal toxic shock syndrome (STSS) during pregnancy. The genome sequence will provide new insights into the mechanisms underlying STSS.

  12. Aflatoxin M1 in samples of "minas" cheese commercialized in the city of Belo Horizonte - Minas Gerais/Brazil Aflotoxina M1 em amostras de queijo "minas" comercializada na cidade de Belo Horizonte - Minas Gerais/ Brasil

    Directory of Open Access Journals (Sweden)

    Guilherme PRADO

    2000-12-01

    Full Text Available Milk products such as cheeses may be contaminated by aflatoxin M1 when dairy cattle have consumed feeds contaminated with aflatoxin B1. Samples of "Minas" cheeses (fresh, canastra and standard were collected by the Inspection Service in the Mercado Central in Belo Horizonte city, Minas Gerais - Brazil. A purified extract was obtained by extraction with dichloromethane followed by a washing with n-hexane and immunoaffinity column purification. The quantification of aflatoxin M1 was done by high performance liquid chromatography (HPLC using a fluorescence detector. Recoveries were about 75%. In 56 of the 75 samples (74.7%, the presence of aflatoxin M1 was detected in concentrations ranging between 0.02 and 6.92ng/g of cheese. In the positive cases ( > or = 0.02ng/g the mean contamination level of aflatoxin M1 was 0.08ng/g in fresh cheese, 0.36ng/g in canastra cheese and 0.62ng/g in standard cheese. No aflatoxin M1 maximum tolerance level in cheese has been established in Brazil.Produtos derivados de leite, como queijo, podem estar contaminados com aflatoxina M1 quando o gado leiteiro consome ração contaminada com aflatoxina B1. Amostras de queijo "Minas" ( frescal, canastra e padrão foram coletados pela Vigilância Sanitária de Minas Gerais - Brasil. Foi obtido um extrato purificado através de extração com diclorometano, seguido de lavagem com n-hexano e purificação em coluna de imunoafinidade. A quantificação da aflatoxina M1 foi feita por cromatografia líquida de alta eficiência (CLAE usando detetor de fluorescência. Os valores de recuperação foram em torno de 75%. A presença de aflatoxina M1 foi detectada em 56 das 75 amostras (74,7% e a faixa de concentração observada foi 0,02 a 6,92ng/g de queijo. Dentre os valores positivos ( > ou = 0,02ng/g a média de contaminação de aflatoxina M1 foi 0,08ng/g para queijo frescal, 0,36ng/g para queijo canastra e 0,62ng/g para queijo padrão. O Brasil não apresenta nível de toler