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Sample records for tissue kallikrein b1

  1. Identification, purification, and localization of tissue kallikrein in rat heart.

    OpenAIRE

    Xiong, W; Chen, L M; Woodley-Miller, C; Simson, J A; Chao, J

    1990-01-01

    A tissue kallikrein has been isolated from rat heart extracts by DEAE-Sepharose and aprotinin-affinity column chromatography. The purified cardiac enzyme has both N-tosyl-L-arginine methyl ester esterolytic and kinin-releasing activities, and displays parallelism with standard curves in a kallikrein radioimmunoassay, indicating it to have immunological identity with tissue kallikrein. The enzyme is inhibited by aprotinin, antipain, leupeptin and by high concentrations of soybean trypsin inhib...

  2. Critical role of tissue kallikrein in vessel formation and maturation : Implications for therapeutic revascularization

    NARCIS (Netherlands)

    Stone, O.A.; Richer, C.; Emanueli, C.; Weel, V. van; Quax, P.H.A.; Katare, R.; Kraenkel, N.; Campagnolo, P.; Barcelos, L.S.; Siragusa, M.; Sala-Newby, G.B.; Baldessari, D.; Mione, M.; Vincent, M.P.; Benest, A.V.; Al Haj Zen, A.; Gonzalez, J.; Bates, D.O.; Alhenc-Gelas, F.; Madeddu, P.

    2009-01-01

    OBJECTIVE : Human Tissue Kallikrein (hKLK1) overexpression promotes an enduring neovascularization of ischemic tissue, yet the cellular mechanisms of hKLK1-induced arteriogenesis remain unknown. Furthermore, no previous study has compared the angiogenic potency of hKLK1, with its loss of function

  3. A cytocidal tissue kallikrein isolated from mouse submandibular glands.

    Science.gov (United States)

    Murakami, K; Ikigai, H; Nagumo, N; Tomita, M; Shimamura, T

    1989-11-06

    A cytocidal factor against mouse thymocytes was purified from the submandibular glands of female BALB/c mice using Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. SDS-PAGE and amino acid sequence analysis revealed that the cytocidal factor was mouse glandular kallikrein (mGK)-6. mGK-6 showed an optimal enzyme activity at pH 10 and a cytocidal activity against thymocytes in a dose-dependent manner.

  4. Preclinical characterization of recombinant human tissue kallikrein-1 as a novel treatment for type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Tadeusz Kolodka

    Full Text Available Modulation of the kallikrein-kinin system (KKS has been shown to have beneficial effects on glucose homeostasis and several other physiological responses relevant to the progression of type 2 diabetes mellitus (T2D. The importance of bradykinin and its receptors in mediating these responses is well documented, but the role of tissue kallikrein-1, the protease that generates bradykinin in situ, is much less understood. We developed and tested DM199, recombinant human tissue kallikrein-1 protein (rhKLK-1, as a potential novel therapeutic for T2D. Hyperinsulinemic-euglycemic clamp studies suggest that DM199 increases whole body glucose disposal in non-diabetic rats. Single-dose administration of DM199 in obese db/db mice and ZDF rats, showed an acute, dose-dependent improvement in whole-body glucose utilization. Sub-acute dosing for a week in ZDF rats improved glucose utilization, with a concomitant rise in fasting insulin levels and HOMA1-%B scores. After cessation of sub-acute dosing, fasting blood glucose levels were significantly lower in ZDF rats during a drug wash-out period. Our studies show for the first time that DM199 administration results in acute anti-hyperglycemic effects in several preclinical models, and demonstrate the potential for further development of DM199 as a novel therapeutic for T2D.

  5. Discovery of novel transcripts of the human tissue kallikrein (KLK1) and kallikrein-related peptidase 2 (KLK2) in human cancer cells, exploiting Next-Generation Sequencing technology.

    Science.gov (United States)

    Adamopoulos, Panagiotis G; Kontos, Christos K; Scorilas, Andreas

    2018-03-31

    Tissue kallikrein, kallikrein-related peptidases (KLKs), and plasma kallikrein form the largest group of serine proteases in the human genome, sharing many structural and functional properties. Several KLK transcripts have been found aberrantly expressed in numerous human malignancies, confirming their prognostic or/and diagnostic values. However, the process of alternative splicing can now be studied in-depth due to the development of Next-Generation Sequencing (NGS). In the present study, we used NGS to discover novel transcripts of the KLK1 and KLK2 genes, after nested touchdown PCR. Bioinformatics analysis and PCR experiments revealed a total of eleven novel KLK transcripts (two KLK1 and nine KLK2 transcripts). In addition, the expression profiles of each novel transcript were investigated with nested PCR experiments using variant-specific primers. Since KLKs are implicated in human malignancies, qualifying as potential biomarkers, the quantification of the presented novel transcripts in human samples may have clinical applications in different types of cancer. Copyright © 2018. Published by Elsevier Inc.

  6. Structure and chromosomal localization of the human renal kallikrein gene

    International Nuclear Information System (INIS)

    Evans, B.A.; Yun, Z.X.; Close, J.A.

    1988-01-01

    Glandular kallikreins are a family of proteases encoded by a variable number of genes in different mammalian species. In all species examined, however, one particular kallikrein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. This kallikrein is found in the kidney, pancreas, and salivary gland, showing a unique pattern of tissue-specific expression relative to other members of the family. The authors have isolated a genomic clone carrying the human renal kallikrein gene and compared the nucleotide sequence of its promoter region with those of the mouse renal kallikrein gene and another mouse kallikrein gene expressed in a distinct cell type. They find four sequence elements conserved between renal kallikrein genes from the two species. They have also shown that the human gene is localized to 19q13, a position analogous to that of the kallikrein gene family on mouse chromosome 7

  7. Tissue kallikrein protects neurons from hypoxia/reoxygenation-induced cell injury through Homer1b/c.

    Science.gov (United States)

    Su, Jingjing; Tang, Yuping; Zhou, Houguang; Liu, Ling; Dong, Qiang

    2012-11-01

    Previous studies have demonstrated that human tissue kallikrein (TK) gene delivery protects against mouse cerebral ischemia/reperfusion (I/R) injury through bradykinin B2 receptor (B2R) activation. We have also reported that exogenous TK administration can suppress glutamate- or acidosis-induced neurotoxicity through the extracellular signal-regulated kinase1/2 (ERK1/2) pathway. To further explore the neuroprotection mechanisms of TK, in the present study we performed immunoprecipitation analysis and identified a scaffolding protein Homer1b/c using MALDI-TOF MS analysis. Here, we tested the hypothesis that TK reduces cell injury induced by oxygen and glucose deprivation/reoxygenation (OGD/R) through activating Homer1b/c. We found that TK increased the expression of Homer1b/c in a concentration- and time-dependent manner. Moreover, TK facilitated the translocation of Homer1b/c to the plasma membrane under OGD/R condition by confocal microscope assays. We also observed that overexpression of Homer1b/c showed the neuroprotection against OGD/R-induced cell injury by enhancing cell survival, reducing LDH release, caspase-3 activity and cell apoptosis. However, the knockdown of Homer1b/c by small interfering RNA showed the opposite effects, indicating that Homer1b/c had protective effects against OGD/R-induced neuronal injury. More interestingly, TK exerted its much more significantly neuroprotective effects after Homer1b/c overexpression, whereas it exerted its reduced effects after Homer1b/c knockdown. In addition, TK pretreatment increased the phosphorylation of the ERK1/2 and Akt-GSK3β through Homer1b/c activation. The beneficial effects of Homer1b/c were abolished by the ERK1/2 or PI3K antagonist. Therefore, we propose novel signaling mechanisms involved in the anti-hypoxic function of TK through activation of Homer1b/c-ERK1/2 and Homer1b/c-PI3K-Akt signaling pathways. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. DISTRIBUTION Of AFLATOXIN B1 FROM POULTRY FEED TO DIFFERENT BODY TISSUES OF BROILERS

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    Farida Begum, A. Rehman1, G. Maliha and J. Nuzhat

    2001-07-01

    Full Text Available This study was carried out to know the distribution of aflatoxin B1 In various edible tissues of broilers from poultry feed at the stage of marketing. For this purpose liver, kidney, dressed meat and poultry feed of the representative flocks were collected and oven dried. The aflatoxin B1 contents of the samples were .e; determined through thin layer chromatography, The data thus collected were statistically analyzed and the results showed that the aflatoxin B1 level was higher (P<0.01 in liver as compared to kidneys and meat.

  9. Plasma extravasation mediated by lipopolysaccharide-induction of kinin B1 receptors in rat tissues

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    Paulo Roberto Wille

    2001-01-01

    Full Text Available The present study was performed to: (a evaluate the effects of kinin B1 (Sar{D-Phe8}-des-Arg9-BK; 10 nmol/kg and B2 (bradykinin (BK; 10 nmol/kg receptor agonists on plasma extravasation in selected rat tissues; (b determine the contribution of a lipopolysaccharide (LPS (100 μ g/kg to the effects triggered by B1 and B2 agonists; and (c characterize the selectivity of B1 ({Leu8}desArg9-BK; 10 nmol/kg and B2 (HOE 140; 10 nmol/kg antagonists as inhibitors of this kinin-induced phenomenon. B1 and B2 agonists were shown to increase plasma extravasation in the duodenum, ileum and also in the urinary bladder of the rat. LPS pretreatment enhanced the plasma extravasation mediated only by the B1 agonist in the duodenum, ileum, trachea, main and segmentar bronchi. These effects were prevented by the B1. but not the B2 antagonist. In normal rats, the B2 antagonist inhibited the effect of B2 agonist in all the tissues analyzed. However, in LPS-treated rats, the B2 antagonist was ineffective in the urinary bladder.

  10. Immunochemical Studies of Plasma Kallikrein

    Science.gov (United States)

    Bagdasarian, Andranik; Lahiri, Biswajit; Talamo, Richard C.; Wong, Pat; Colman, Robert W.

    1974-01-01

    A monospecific antibody against human plasma kallikrein has been prepared in rabbits with kallikrein further purified to remove gamma globulins. The antisera produced contained antikallikrein and also anti-IgG, in spite of only 8% contamination of kallikrein preparation with IgG. The latter antibody was removed by adsorption of antisera with either Fletcher factor-deficient plasma or with purified IgG. Both kallikrein and prekallikrein (in plasma) cross-react with the antibody with no apparent difference between the precipitation arcs developed during immunoelectrophoresis and no significant difference in reactivity when quantified by radial immunodiffusion. Kallikrein antibody partially inhibits the esterolytic and fully inhibits the proteolytic activity of kallikrein. In addition, the antibody inhibits the activation of prekallikrein, as measured by esterase or kinin release. The magnitude of the inhibition is related to the molecular weight of the activator used. Thus, for the four activators tested, the greatest inhibition is observed with kaolin and factor XIIA, while large activator and the low molecular weight prekallikrein activators are less inhibited. With the kallikrein antibody, the incubation of kallikrein with either plasma or partially purified C1 esterase inactivator results in a new precipitin arc, as detected by immunoelectrophoresis. This finding provides physical evidence for the interaction of the enzyme and inhibitor. No new arc could be demonstrated between kallikrein and α2-macroglobulin, or α1-antitrypsin, although the concentration of free kallikrein antigen decreases after interaction with the former inhibitor. By radial immunodiffusion, plasma from healthy individuals contained 103±13 μg/ml prekallikrein antigen. Although in mild liver disease, functional and immunologic kallikrein are proportionally depressed, the levels of prekallikrein antigen in plasma samples from patients with severe liver disease remains 40% of normal, while

  11. Testing an aflatoxin B1 gene signature in rat archival tissues.

    Science.gov (United States)

    Merrick, B Alex; Auerbach, Scott S; Stockton, Patricia S; Foley, Julie F; Malarkey, David E; Sills, Robert C; Irwin, Richard D; Tice, Raymond R

    2012-05-21

    Archival tissues from laboratory studies represent a unique opportunity to explore the relationship between genomic changes and agent-induced disease. In this study, we evaluated the applicability of qPCR for detecting genomic changes in formalin-fixed, paraffin-embedded (FFPE) tissues by determining if a subset of 14 genes from a 90-gene signature derived from microarray data and associated with eventual tumor development could be detected in archival liver, kidney, and lung of rats exposed to aflatoxin B1 (AFB1) for 90 days in feed at 1 ppm. These tissues originated from the same rats used in the microarray study. The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue. The qPCR FFPE liver results were compared to the original liver microarray data and to qPCR results using RNA from fresh frozen liver. Archival liver paraffin blocks yielded 30 to 50 μg of degraded RNA that ranged in size from 0.1 to 4 kB. qPCR results from FFPE and fresh frozen liver samples were positively correlated (p ≤ 0.05) by regression analysis and showed good agreement in direction and proportion of change with microarray data for 11 of 14 genes. All 14 transcripts could be amplified from FFPE kidney RNA except the glutamate receptor gene Grin2c; however, only Abcb1b was significantly upregulated from control. Abundant constitutive transcripts, S18 and β-actin, could be amplified from lung FFPE samples, but the narrow RNA size range (25-500 bp length) prevented consistent detection of target transcripts. Overall, a discrete gene signature derived from prior transcript profiling and representing cell cycle progression, DNA damage response, and xenosensor and detoxication pathways was successfully applied to archival liver and kidney by qPCR and indicated that gene expression changes in response to subchronic AFB1 exposure occurred predominantly in the liver, the primary target for AFB1-induced

  12. Cloning and tissue expression of cytochrome P450 1B1 and 1C1 ...

    African Journals Online (AJOL)

    Cytochrome P450 1 (CYP1) is widely used as an indicator of exposure to environmental contaminants. In the study, two full-length complementary DNAs encode for CYP1B1 and CYP1C1 were cloned from medaka liver exposed to 500 ppb β-naphthoflavone for 24 h. CYP1B1, having 1984 bp, contains an open reading ...

  13. Radioimmunoassay of human urinary kallikrein

    International Nuclear Information System (INIS)

    Goering, W.

    1980-01-01

    Using a human urinary kallikrein, purified by means of Trasylol sepharose, it has been possible to develop a radioimmunoassay of kallikrein capable of detecting the substance down to a concentration of 0.5 ng/ml. The specific activity of the tracer labelled with 125-iodine using the Chloramine-T method was 30-70 nCi/ng of kallikrein. The antiserum titres for the antikallikrein serum were 1:20.000 up to 1:50.000. Human urine, submandibular and parotid salivae as well as pancreatic secretion in this RIA reacted in the same manner as the kallikrein standard solution. The kallikrein content in urine, as determined by the RIA was between 0 and 300 ng/ml, in the saliva between 400 and 2.000 ng/ml, and in the pancreatic juice between 300 and 12.000 ng/ml. Using human serum, only an incomplete immunological cross-reaction could be achieved. In human liquor as well as in animal preparation, no cross-reacting substances could be detected. (orig.) [de

  14. The Long-Term Outcome Comparison of Different Time-Delayed Kallikrein Treatments in a Mouse Cerebral Ischemic Model

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    Yaohui Ni

    2018-01-01

    Full Text Available Delayed administration of kallikrein after cerebral infarction can improve neurological function. However, the appropriate kallkrein treatment time after ischemic stroke has not been illuminated. In this study, we compared the long-term outcome among three kallikrein therapeutic regimens starting at different time points following mouse cerebral ischemia. Furthermore, the protective mechanisms involving neurogenesis, angiogenesis, and AKT-GSK3β-VEGF signaling pathway were analyzed. Human tissue kallikrein was injected through the tail vein daily starting at 8 h, 24 h, or 36 h after right middle cerebral artery occlusion (MCAO until the 28th day. Three therapeutic regimens all protected against neurological dysfunction, but kallikrein treatment starting at 8 h after MCAO had the best efficacy. Additionally, kallikrein treatment at 8 h after MCAO significantly enhanced cell proliferation including neural stem cell and induced differentiation of neural stem cell into mature neuron. Kallikrein treatment starting at 8 h also promoted more angiogenesis than other two treatment regimens, which was associated with AKT-GSK3β-VEGF signaling pathway. Thus, we confirm that three delayed kallikrein treatments provide protection against cerebral infarction and furthermore suggest that kallikrein treatment starting at 8 h had a better effect than that at 24 h and 36 h. These findings provide the experimental data contributing to better clinical application of exogenous kallikrein.

  15. Kallikrein-like amidase activity in renal ischemia and reperfusion

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    M.D. Carattino

    2000-05-01

    Full Text Available We assessed a kallikrein-like amidase activity probably related to the kallikrein-kinin system, as well as the participation of leukocyte infiltration in renal ischemia and reperfusion. Male C57BL/KSJmdb mice were subjected to 20 or 60 min of ischemia and to different periods of reperfusion. A control group consisted of sham-operated mice, under similar conditions, except for ischemia induction. Kallikrein-like amidase activity, Evans blue extravasation and myeloperoxidase activity were measured in kidney homogenates, previously perfused with 0.9% NaCl. Plasma creatinine concentration increased only in the 60-min ischemic group. After 20 min of ischemia and 1 or 24 h of reperfusion, no change in kallikrein-like amidase activity or Evans blue extravasation was observed. In the mice subjected to 20 min of ischemia, edema was evident at 1 h of reperfusion, but kidney water content returned to basal levels after 24 h of reperfusion. In the 60-min ischemic group, kallikrein-like amidase activity and Evans blue extravasation showed a similar significant increase along reperfusion time. Kallikrein-like amidase activity increased from 4 nmol PNA mg protein-1 min-1 in the basal condition to 15 nmol PNA mg protein-1 min-1 at 10 h of reperfusion. For dye extravasation the concentration measured was near 200 µg of Evans blue/g dry tissue in the basal condition and 1750 µg of Evans blue/g dry tissue at 10 h of reperfusion. No variation could be detected in the control group. A significant increase from 5 to 40 units of DAbs 655 nm g wet tissue-1 min-1 in the activity of the enzyme myeloperoxidase was observed in the 60-min ischemic group, when it was evaluated after 24 h of reperfusion. Histological analysis of the kidneys showed migration of polymorphonuclear leukocytes from the vascular bed to the interstitial tissue in the 60-min ischemic group after 24 h of reperfusion. We conclude that the duration of ischemia is critical for the development of damage

  16. Expression of kallikrein-related peptidase 7 is decreased in prostate cancer

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    Chong-Yu Zhang

    2015-02-01

    Full Text Available Recent evidence suggests that the human kallikrein 7 (KLK7 is differentially regulated in a variety of tumors. The aim of this study was to determine the expression of kallikrein-related peptidase 7 and KLK7 in our large collection of prostate samples. Between August 2000 and December 2012, 116 patients with histologically confirmed prostate cancer (PCa and 92 with benign prostate hyperplasia (BPH were recruited into the study. Using immunohistochemistry, quantitative reverse transcription polymerase chain reaction (RT-PCR and western blot, kallikrein-related peptidase 7 expression in BPH and PCa tissues was determined at the mRNA and protein levels. The relationships between kallikrein-related peptidase 7 mRNA expression and clinicopathological features were analyzed. A total of 64 of 92 (69.57% benign cases showed positive staining for KLK7 and 23 of 116 (19.83% malignant cases showed positive, the difference of KLK7 expression between PCa and BPH was statistically significant (P < 0.001. The expression level of kallikrein-related peptidase 7 mRNA was significantly decreased in PCa tissues compared with that in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 mRNA exhibited different expression patterns in terms of localization depending on pathological category of PCa. Similarly, our western immunoblot analyses demonstrated that the protein expression levels of KLK7 was lower in PCa than in BPH tissues and normal prostate tissue. Kallikrein-related peptidase 7 and KLK7 expression are down-regulated in PCa and lower expression of kallikrein-related peptidase 7 closely correlates with higher Gleason score and higher prostate-specific antigen level.

  17. Calibrated kallikrein generation in human plasma

    DEFF Research Database (Denmark)

    Biltoft, D; Sidelmann, J J; Olsen, L F

    2016-01-01

    generation method as a template. RESULTS: A suitable kallikrein specific fluorogenic substrate was identified (KM=0.91mM, kcat=19s(-1)), and kallikrein generation could be measured in undiluted plasma when silica was added as activator. Disturbing effects, including substrate depletion and the inner......-filter effect, however, affected the signal. These problems were corrected for by external calibration with α2-macroglobulin-kallikrein complexes. Selectivity studies of the substrate, experiments with FXII and PK depleted plasmas, and plasma with high or low complement C1-esterase inhibitor activity indicated...

  18. Prognostic significance of multiple kallikreins in high-grade astrocytoma

    International Nuclear Information System (INIS)

    Drucker, Kristen L.; Gianinni, Caterina; Decker, Paul A.; Diamandis, Eleftherios P.; Scarisbrick, Isobel A.

    2015-01-01

    Kallikreins have clinical value as prognostic markers in a subset of malignancies examined to date, including kallikrein 3 (prostate specific antigen) in prostate cancer. We previously demonstrated that kallikrein 6 is expressed at higher levels in grade IV compared to grade III astrocytoma and is associated with reduced survival of GBM patients. In this study we determined KLK1, KLK6, KLK7, KLK8, KLK9 and KLK10 protein expression in two independent tissue microarrays containing 60 grade IV and 8 grade III astrocytoma samples. Scores for staining intensity, percent of tumor stained and immunoreactivity scores (IR, product of intensity and percent) were determined and analyzed for correlation with patient survival. Grade IV glioma was associated with higher levels of kallikrein-immunostaining compared to grade III specimens. Univariable Cox proportional hazards regression analysis demonstrated that elevated KLK6- or KLK7-IR was associated with poor patient prognosis. In addition, an increased percent of tumor immunoreactive for KLK6 or KLK9 was associated with decreased survival in grade IV patients. Kaplan-Meier survival analysis indicated that patients with KLK6-IR < 10, KLK6 percent tumor core stained < 3, or KLK7-IR < 9 had a significantly improved survival. Multivariable analysis indicated that the significance of these parameters was maintained even after adjusting for gender and performance score. These data suggest that elevations in glioblastoma KLK6, KLK7 and KLK9 protein have utility as prognostic markers of patient survival. The online version of this article (doi:10.1186/s12885-015-1566-5) contains supplementary material, which is available to authorized users

  19. Increased synovial tissue NF-kappa B1 expression at sites adjacent to the cartilage-pannus junction in rheumatoid arthritis.

    NARCIS (Netherlands)

    Benito, M.J.; Murphy, E.P.; Berg, W.B. van den; Fitzgerald, O.; Bresnihan, B.

    2004-01-01

    OBJECTIVE: To compare the expression of the Rel/NF-kappa B subunits, NF-kappa B1 (p50) and RelA (p65), in paired synovial tissue samples selected from sites adjacent to and remote from the cartilage-pannus junction (CPJ) in patients with inflammatory arthritis. METHODS: Synovial tissue was selected

  20. Effect of focal irradiation on plasma kallikrein activity in tumor bearing rats

    International Nuclear Information System (INIS)

    Makoyo, P.O.Z.R.; West, W.L.

    1977-01-01

    The activated plasma kallikrein from tumor bearing rats before and after focal irradiation of the hind limbs was measured by the hydrolysis of 0.015M N-(p-toluene sulfonyl)-L arginine methyl ester (TAME). Blood was collected from abdominal aorta of rats anesthetized with diethyl ether into plastic tubes containing 1 volume of 3.8 percent sodium citrate for each 9 volumes. Plasma was isolated by centrifugation (2000 g) at 4 0 C. Small pieces of minced tumor tissue were inserted in a trochar and inoculated in the hind limbs of the rats. Morris hepatomas 7777 and 3924A were transplanted subcutaneously over the hind legs while Walker 256 tumor was transplanted intramuscularly in the hind limbs. Plasma kallikrein (μm TAME utilized/ml/hr) was decreased in three different groups of tumor bearing rats: Walker tumor from 207 +- 34 to 114 +- 30 Hepatoma 7777 from 219 +- 13 to 106 +- 3 and Hepatoma 3924A from 227 +- 7 to 133 +- 5. Two hours after focal irradiation (1000 R) plasma kallikrein decreased further in Walker tumor and hepatoma 7777 to 55 +- 5 and 96 +- 3.6 respectively. The plasma of tumor bearing rats becomes deficient in kallikrein at about the time metastases may be identified. The acute fall in plasma kallikrein is consistent with the overall stress mechanism

  1. Lack of plasma kallikrein-kinin system cascade in teleosts.

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    Marty Kwok-Shing Wong

    Full Text Available The kallikrein-kinin system (KKS consists of two major cascades in mammals: "plasma KKS" consisting of high molecular-weight (HMW kininogen (KNG, plasma kallikrein (KLKB1, and bradykinin (BK; and "tissue KKS" consisting of low molecular-weight (LMW KNG, tissue kallikreins (KLKs, and [Lys(0]-BK. Some components of the KKS have been identified in the fishes, but systematic analyses have not been performed, thus this study aims to define the KKS components in teleosts and pave a way for future physiological and evolutionary studies. Through a combination of genomics, molecular, and biochemical methods, we showed that the entire plasma KKS cascade is absent in teleosts. Instead of two KNGs as found in mammals, a single molecular weight KNG was found in various teleosts, which is homologous to the mammalian LMW KNG. Results of molecular phylogenetic and synteny analyses indicated that the all current teleost genomes lack KLKB1, and its unique protein structure, four apple domains and one trypsin domain, could not be identified in any genome or nucleotide databases. We identified some KLK-like proteins in teleost genomes by synteny and conserved domain analyses, which could be the orthologs of tetrapod KLKs. A radioimmunoassay system was established to measure the teleost BK and we found that [Arg(0]-BK is the major circulating form instead of BK, which supports that the teleost KKS is similar to the mammalian tissue KKS. Coincidently, coelacanths are the earliest vertebrate that possess both HMW KNG and KLKB1, which implies that the plasma KKS could have evolved in the early lobe-finned fish and descended to the tetrapod lineage. The co-evolution of HMW KNG and KLKB1 in lobe-finned fish and early tetrapods may mark the emergence of the plasma KKS and a contact activation system in blood coagulation, while teleosts may have retained a single KKS cascade.

  2. Plasminogen-independent initiation of the pro-urokinase activation cascade in vivo. Activation of pro-urokinase by glandular kallikrein (mGK-6) in plasminogen-deficient mice

    DEFF Research Database (Denmark)

    List, K; Jensen, Ole Nørregaard; Bugge, T H

    2000-01-01

    )-antitrypsin. We suggest that mouse glandular kallikrein mGK-6 is an activator of pro-uPA in the mouse urinary tract in vivo. Since this kallikrein is expressed in a number of tissues and also occurs in plasma, it can also be considered a candidate for a physiological pro-uPA activator in other locations....

  3. Adipose tissue PCB levels and CYP1B1 and COMT genotypes in relation to breast cancer risk in postmenopausal Danish women

    DEFF Research Database (Denmark)

    Bräuner, Elvira V; Loft, Steffen; Wellejus, Anja

    2014-01-01

    these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk....... When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We...

  4. Development of a radioimmunoassay for pig pancreatic kallikrein and its application in physiological studies

    International Nuclear Information System (INIS)

    Fink, E.; Guettel, C.; Seifert, J.

    1978-01-01

    A RIA for pig pancreatic kallikrein has been developed. Purified kallikrein was labelled with 125 I. The use of radioimmunoassays in investigating the intestinal absorption of pig pancreas kallikrein is dealt with. (VJ) [de

  5. Development of a radioimmunoassay for pig pancreatic kallikrein

    Energy Technology Data Exchange (ETDEWEB)

    Fink, E; Guettel, C [Muenchen Univ. (Germany, F.R.). Chirurgische Klinik

    1978-07-01

    A radioimmunoassay for the determination of pig pancreatic kallikrein was developed. The chloramine-T method was employed for the labelling of the antigen with /sup 125/I. The assay allows the determination of kallikrein in concentrations as low as 0.4 ..mu..g/l. Pig urinary and pig submandibular kallikreins are indistinguishable from pig pancreatic kallikrein by the assay. No cross reactivity was observed for bovine trypsin and chymotrypsin, porcine trypsin and kallikreins of guinea pig submandibular glands and guinea pig coagulation glands. Because of the high specificity of the assay, which is not attainable with conventional assays based on the enzymatic activity, the radioimmunoassay is highly suited for investigations into the physiological role and the pharmacological mechanism of action of pig glandular kallikreins.

  6. What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

    Institute of Scientific and Technical Information of China (English)

    Maria; da; Graa; Naffah-Mazzacoratti; Telma; Luciana; Furtado; Gouveia; Priscila; Santos; Rodrigues; Simōes; Sandra; Regina; Perosa

    2014-01-01

    The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.

  7. Characterization of elements of the kallikrein-kinin system in rainbow trout (Salmo gairdneri)

    International Nuclear Information System (INIS)

    Lipke, D.W.

    1988-01-01

    Elements of kallikrein-kinin system (KKS) are found in anamniotic vertebrates, however, research has failed to substantiate the presence of a KKS in these animals. This research was conducted to verify the presence of elements of the KKS in rainbow trout. Trout branchial angiotensin-converting enzyme (ACE, kininase II) was similar to mammalian ACE in many physical, chemical and kinetic parameters. Angiotensin-converting enzyme-like activity (ACELA) was also demonstrated in the most primitive vertebrates. ACELA was consistently found in vertebrate respiratory tissues and was prevalent in salt and water exchanging organs. 3 H-bradykinin, perfused through the trout gill was not metabolized, as demonstrated by high voltage paper electrophoresis. However, trout gills extracted and retained approximately 40% of the 3 H-bradykinin perfused into the branchial vasculature. Gill tissue homogenates metabolized both 3 H-bradykinin and the vasoactive substance produced by incubating trout plasma with glandular kallikrein

  8. Inhibition of plasma kallikrein-kinin system to alleviate renal injury and arthritis symptoms in rats with adjuvant-induced arthritis.

    Science.gov (United States)

    Zhu, Jie; Wang, Hui; Chen, Jingyu; Wei, Wei

    2018-04-01

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Impairment of kidney functions in RA was observed. However, the mechanism of kidney injury of RA has not been clear. Plasma kallikrein-kinin system (KKS) was involved in inflammatory processes in kidney disease. This study aimed to explore the role of plasma KKS in immune reactions and kidney injury of RA. The paw of AA rats appeared to be swelling and redness, the arthritis index was significantly increased on the 18, 21 and 24 d after injection and secondary inflammation in multi-sites was observed. Kidney dysfunction accompanied with inflammatory cell infiltration, tubular epithelial cell mitochondrial swelling and vacuolar degeneration, renal glomerular foot process fusions and glomerular basement membrane thickening were observed in AA rats. The expressions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (Kim-1) in kidney of AA rats were increased. In addition, expressions of BK, PK, B1R and B2R in the renal tissue of AA rats were up-regulated. Pro-inflammatory cytokines IL-2, IFN-γ and TNF-α were increased and anti-inflammatory cytokines IL-4 and IL-10 were low in kidney. Plasma kallikrein (PK) inhibitor PKSI-527 attenuated arthritis signs and renal damage, and inhibited BK, PK, B1R and B2R expressions. The protein expressions of P38, p-P38 and p-JNK and IFN-γ and TNF-α were inhibited by PKSI-527. These findings demonstrate that plasma KKS activation contributed to the renal injury of AA rats through MAPK signaling pathway. Plasma KKS might be a potential target for RA therapy.

  9. Kallikrein and Renin in the Membrane Fractions of the Rat Kidney.

    Science.gov (United States)

    1980-05-23

    fraction. PM-kallikrein re- leased a kinin, cleaved the peptide substrate, S-2266 and a radio-labeled arginine ester. The ester was also hydrolyzed by renal...more by activators of kallikrein, e.g. by phospholipase A/, lyso- lecithin and melittin. Low sodium diet increased the activity of kallikrein in the...peptide substrate, S-2266 and a radio- labeled arginine ester. The ester was also hydrolyzed by renal enzymes other than kallikrein. PM-kallikrein was

  10. Toxicokinetics of fumonisin B1 in turkey poults and tissue persistence after exposure to a diet containing the maximum European tolerance for fumonisins in avian feeds.

    Science.gov (United States)

    Tardieu, Didier; Bailly, Jean-Denis; Skiba, Fabien; Grosjean, François; Guerre, Philippe

    2008-09-01

    The kinetic of fumonisin B1 (FB1) after a single IV and oral dose, and FB1 persistence in tissue were investigated in turkey poults by HPLC after purification of samples on columns. After IV administration (single-dose: 10mg FB1/kg bw), serum concentration-time curves were best described by a three-compartment open model. Elimination half-life and mean residence time of FB1 were 85 and 52min, respectively. After oral administration (single-dose: 100mg FB1/kg bw) bioavailability was 3.2%; elimination half-life and mean residence time were 214 and 408min, respectively. Clearance of FB1 was 7.6 and 7.5ml/min/kg for IV and oral administration, respectively. Twenty-four hours after the administration of FB1 by the intravenous route, liver and kidney contained the highest levels of FB1 in tissues, level in muscle was low or below the limit of detection (LD, 13microg/kg). The persistence of FB1 in tissue was also studied after administration for 9 weeks of a feed that contained 5, 10 and 20mg FB1+FB2/kg diet. Eight hours after the last intake of 20mg FB1+FB2/kg feed (maximum recommended concentration of fumonisins established by the EU for avian feed), hepatic and renal FB1 concentrations were 119 and 22microg/kg, level in muscles was below the LD.

  11. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    Energy Technology Data Exchange (ETDEWEB)

    Aburto, Andrés [Program of M.Sc., Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Barría, Agustín [School of Biochemistry, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Cárdenas, Areli [Ph.D. Program, Faculty of Sciences, Universidad Austral de Chile, Valdivia (Chile); Carpio, Daniel; Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia (Chile); Burgos, Maria E. [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile); Ardiles, Leopoldo, E-mail: leopoldoardiles@gmail.com [Department of Nephrology, Faculty of Medicine, Universidad Austral de Chile, Valdivia (Chile)

    2014-10-15

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity.

  12. Pre-stimulation of the kallikrein system in cisplatin-induced acute renal injury: An approach to renoprotection

    International Nuclear Information System (INIS)

    Aburto, Andrés; Barría, Agustín; Cárdenas, Areli; Carpio, Daniel; Figueroa, Carlos D.; Burgos, Maria E.; Ardiles, Leopoldo

    2014-01-01

    Antineoplastic treatment with cisplatin is frequently complicated by nephrotoxicity. Although oxidative stress may be involved, the pathogenic mechanisms responsible for renal damage have not been completely clarified. In order to investigate the role of the renal kinin system in this condition, a group of rats was submitted to high potassium diet to stimulate the synthesis and excretion of tissue kallikrein 1 (rKLK1) previous to an intraperitoneal injection of 7 mg/kg cisplatin. A significant reduction in lipoperoxidation, evidenced by urinary excretion of malondialdehyde and renal immunostaining of hidroxy-nonenal, was accompanied by a decline in apoptosis. Coincident with these findings we observed a reduction in the expression of renal KIM-1 suggesting that renoprotection may be occurring. Stimulation or indemnity of the renal kinin system deserves to be evaluated as a complementary pharmacological measure to diminish cisplatin nephrotoxicity. - Highlights: • Mechanisms of cisplatin-induced-renal damage have not been completely clarified. • Cisplatin induces oxidative stress and apoptosis. • The renal kallikrein-kinin system is protective in experimental acute renal damage. • Kallikrein stimulation reduces oxidative stress and apoptosis induced by cisplatin. • Protection of the kallikrein-kinin system may reduce cisplatin toxicity

  13. Crystallization and preliminary crystallographic studies of human kallikrein 7, a serine protease of the multigene kallikrein family

    Energy Technology Data Exchange (ETDEWEB)

    Fernández, Israel S. [Departamento de Ciencia de Proteínas, Centro de Investigaciones Biológicas-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain); Ständker, Ludger [Departamento de Ciencia de Proteínas, Centro de Investigaciones Biológicas-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain); Hannover Medical School, Center of Pharmacology, 30625 Hannover (Germany); Forssmann, Wolf-Georg [Hannover Medical School, Center of Pharmacology, 30625 Hannover (Germany); Giménez-Gallego, Guillermo; Romero, Antonio, E-mail: romero@cib.csic.es [Departamento de Ciencia de Proteínas, Centro de Investigaciones Biológicas-CSIC, Ramiro de Maeztu 9, 28040 Madrid (Spain)

    2007-08-01

    The cloning, expression, purification and crystallization of recombinant human kallikrein 7, directly synthesized in the active form in E. coli, is described. Diffraction data were collected to 2.8 Å resolution from native crystals. Human kallikreins are a group of serine proteases of high sequence homology whose genes are grouped as a single cluster at chromosome 19. Although the physiological roles of kallikreins are generally still unknown, members of the kallikrein family have been clearly implicated in pathological situations such as cancer and psoriasis. Human kallikrein 7 (hK7) has been shown to be involved in pathological keratinization, psoriasis and ovarian cancer. In order to gain insight into the molecular structure of this protein, hK7 was crystallized after recombinant production in its folded and active form using a periplasmic secretion vector in Escherichia coli. The crystals belonged to the rhombohedral space group H32 and diffracted to 2.8 Å. The phase problem was solved by molecular replacement using the mouse kallikrein-related protein neuropsin. Completion of the model and structure refinement are under way.

  14. Tissue persistence of fumonisin B1 in ducks and after exposure to a diet containing the maximum European tolerance for fumonisins in avian feeds.

    Science.gov (United States)

    Tardieu, Didier; Bailly, Jean-Denis; Benlashehr, Imad; Auby, Alienor; Jouglar, Jean-Yves; Guerre, Philippe

    2009-12-10

    Toxicity and persistence of fumonisin B1 (FB1) in liver, kidney and muscle were investigated in ducks fed 5, 10 and 20mg FB1+FB2/kg feed during force-feeding. Mortality and signs of toxicity were only obtained with 20mg/kg, whereas an increased Sa/So ratio was observed from 5mg/kg on. Persistence of FB1 was only found in liver (16 and 20 microg FB1/kg liver in ducks fed 10 and 20 mg FB1+FB2/kg feed, respectively). Toxicokinetic studies were conducted by the intravenous route (IV, single dose: 10mg FB1/kg body weight) and the oral route (single dose: 100mg FB1/kg body weight), in growing ducks and in ducks during force-feeding. After IV administration, serum concentration-time curves were described by a two-compartment open model. Elimination half-life and mean residence time of FB1 were 26 and 24 min, respectively, clearance was 19.3 ml/min/kg. After oral administration, bioavailability, elimination half-life, mean residence time and clearance varied during force-feeding and growth from 2-2.3%, 71-80 min, 200-188 min, 16.7-17 ml/min/kg, respectively. Taken together these results demonstrate that the risk of persistence of FB1 in ducks after force-feeding is very low, Sa/So being a good biomarker which increases before signs of toxicity and risk of persistence of FB1 in tissue (limit of detection 13 microg/kg).

  15. Vitamin B1

    Science.gov (United States)

    ... Prize Alfred Nobel's Life and Work Teachers' Questionnaire Vitamin B1 - About The Chicken Farm educational game and ... the game window. Reading: "Christian Eijkman, Beriberi and Vitamin B1" - Who was Eijkman and why did he ...

  16. Enhancement of lymphocyte proliferation by mouse glandular kallikrein.

    Science.gov (United States)

    Hu, Z Q; Murakami, K; Ikigai, H; Shimamura, T

    1992-03-01

    Mouse glandular kallikrein (mGK) strongly enhanced the spontaneous and mitogen-induced proliferation of lymphocytes. Both blast formation and 3H-TdR incorporation were dose-dependently enhanced at the same time many cells were killed. The enhancing activity was independent of EGF, because EGF-binding proteins (mGK-9 in mGK-6,9 mixture and mGK-13), renal kallikrein (mGK-6) and human kallikrein all displayed the same enhancement. A serine proteinase inhibitor, diisopropyl fluorophosphate, could block the enhancement by mGK. The new function suggests that mGK is important in the immune system as a regulatory molecule.

  17. Is the renal kallikrein-kinin system a factor that modulates hypercalciuria?

    Directory of Open Access Journals (Sweden)

    Armando Luis Negri

    2017-01-01

    Full Text Available Renal tubular calcium reabsorption is one of the principal factors that determine serum calcium concentration and calcium excretion. Calcium excretion is regulated by the distal convoluted tubule and connecting tubule, where the epithelial calcium channel TRPV5 can be found, which limits the rate of transcellular calcium transport. The dynamic presence of the TRPV5 channel on the surface of the tubular cell is mediated by an endosomal recycling process. Different intrarenal factors are involved in calcium channel fixation in the apical membrane, including the anti-ageing hormone klotho and tissue kallikrein (TK. Both proteins are synthesised in the distal tubule and secreted in the tubular fluid. TK stimulates active calcium reabsorption through the bradykinin receptor B2 that compromises TRPV5 activation through the protein kinase C pathway. TK-deficient mice show hypercalciuria of renal origin comparable to that seen in TRPV5 knockout mice. There is a polymorphism with loss of function of the human TK gene R53H (allele H that causes a marked decrease in enzymatic activity. The presence of the allele H seems to be common at least in the Japanese population (24%. These individuals have a tendency to greater calcium and sodium excretion in urine that is more evident during furosemide infusion. Future studies should analyse if manipulating the renal kallikrein-kinin system can correct idiopathic hypercalciuria with drugs other than thiazide diuretics.

  18. Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan Sulfate Proteoglycans

    OpenAIRE

    Motta, Guacyara; Tersariol, Ivarne L. S.

    2017-01-01

    Human plasma kallikrein-kinin system proteins are related to inflammation through bradykinin. In the proximity of its target cells, high molecular weight kininogen (H-kininogen) is the substrate of plasma kallikrein, which releases bradykinin from H-kininogen. Heparan sulfate proteoglycans (HSPGs) play a critical role in either recruiting kinin precursors from the plasma, or in the assembly of kallikrein-kinin system components on the cell surface. Furthermore, HSPGs mediate the endocytosis a...

  19. Morpho-functional differences at tissue level in some radents of arid zone: common vole and laboratory mouse C57B1 differing in radioresistance

    International Nuclear Information System (INIS)

    Popova, M.F.; Bulyakova, N.V

    1987-01-01

    An assumption is made, that mechanisms of physiological regenration of the investigation tissues in rodents of arid zones, located in different continents, differ in principle. Physiological regeneration in Rhombomys opimus and meriones unguiculatis inhabiting the Kara Kum desert and the Baikal region mainly occurs in the results of intracellular repair and in Dipodomus merriamy from Mexican Sonora desert - to a great extent by way of intensive cell division and replacement of cellular populations by other ones. The reason for the different detected lies most probably in different ways of evolution of these animals

  20. CYP7B1

    DEFF Research Database (Denmark)

    Roos, P; Svenstrup, K; Danielsen, E R

    2014-01-01

    UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids. Clinica......UNLABELLED: The SPG5A subtype of Hereditary Spastic Paraplegia (HSP) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the CYP7B1 gene, which encodes a steroid cytochrome P450 7α-hydroxylase. This enzyme provides the primary metabolic route for neurosteroids.......945_947 dupGGC p.A316AA). CONCLUSION: SPG5A could be characterized as a predominantly pure HSP. MRS showing elevated mI/Cr ratio in the white matter may be indicative of SPG5A....

  1. Kallistatin Ameliorates Influenza Virus Pathogenesis by Inhibition of Kallikrein-Related Peptidase 1-Mediated Cleavage of Viral Hemagglutinin

    Science.gov (United States)

    Leu, Chia-Hsing; Yang, Mei-Lin; Chung, Nai-Hui; Huang, Yen-Jang; Su, Yu-Chu; Chen, Yi-Cheng; Lin, Chia-Cheng; Shieh, Gia-Shing; Chang, Meng-Ya; Wang, Shainn-Wei; Chang, Yao; Chao, Julie; Chao, Lee

    2015-01-01

    Proteolytic cleavage of the hemagglutinin (HA) of influenza virus by host trypsin-like proteases is required for viral infectivity. Some serine proteases are capable of cleaving influenza virus HA, whereas some serine protease inhibitors (serpins) inhibit the HA cleavage in various cell types. Kallikrein-related peptidase 1 (KLK1, also known as tissue kallikrein) is a widely distributed serine protease. Kallistatin, a serpin synthesized mainly in the liver and rapidly secreted into the circulation, forms complexes with KLK1 and inhibits its activity. Here, we investigated the roles of KLK1 and kallistatin in influenza virus infection. We show that the levels of KLK1 increased, whereas those of kallistatin decreased, in the lungs of mice during influenza virus infection. KLK1 cleaved H1, H2, and H3 HA molecules and consequently enhanced viral production. In contrast, kallistatin inhibited KLK1-mediated HA cleavage and reduced viral production. Cells transduced with the kallistatin gene secreted kallistatin extracellularly, which rendered them more resistant to influenza virus infection. Furthermore, lentivirus-mediated kallistatin gene delivery protected mice against lethal influenza virus challenge by reducing the viral load, inflammation, and injury in the lung. Taking the data together, we determined that KLK1 and kallistatin contribute to the pathogenesis of influenza virus by affecting the cleavage of the HA peptide and inflammatory responses. This study provides a proof of principle for the potential therapeutic application of kallistatin or other KLK1 inhibitors for influenza. Since proteolytic activation also enhances the infectivity of some other viruses, kallistatin and other kallikrein inhibitors may be explored as antiviral agents against these viruses. PMID:26149981

  2. B1 Aerogels

    DEFF Research Database (Denmark)

    Duer, Karsten; Svendsen, Sv Aa Højgaard

    1996-01-01

    , engineering and architectural basis which will support the appropriate use of aerogels in windows, solar collectors and passive solar applications, with the aim of saving or producing thermal energy for use in buildings".This objective is in very good agreement with the general scope of task 18 but where Task...... of aerogel as a material for window applications3. Construction of an aerogel DGU and measurement of key performance parameters. The goal for the aerogel DGU was to reach a Total Solar Energy Transmittance above 0.75 and a U-value below 0.5 W/m²K. These are values that can not be simultaneously reached......The report summarizes the work that has been carried out within the project "B1 AEROGELS" as a part of the IEA SH&CP Task 18 "Advanced Glazing and Associated Materials For Solar And Building Applications".By providing at the same time thermal insulation and transparency the silica aerogel is a very...

  3. aflatoxina b1

    Directory of Open Access Journals (Sweden)

    A. Valdivia

    2004-01-01

    Full Text Available Con el objetivo de probar que la suplementación dietética de ácido elágico (AE o N-Acetilcisteína (NAC en pollos de engorda, atenúa los efectos de una intoxicación aguda por la aflatoxina B1 (AFB1, se intoxicaron con AFB1 pura, tres grupos de diez pollos cada uno (3.0 mb/kg pc, IP. Otros tres grupos recibieron solamente el vehículo (aceite de maíz 2.0 ml/kg pc, IP. Cuatro días antes se administró un alimento testigo, o bien, la misma dieta adicionada con AE (2.5 g/kg o NAC (200 mg/kg pc/6 h. A las 24 horas de la administración de AFB1, se cuantificaron las concentraciones hepáticas de glutatión (GSH, de actividad enzimática específica de la transferasa de glutatión (GST, alanina aminotransferasa, aspartato aminotransferasa y de proteínas hepáticas totales. Los resultados mostraron que NAC atenúa el impacto negativo de la AFB1 sobre el crecimiento corporal y al igual que AE, incrementa la GST y revierte parcialmente los efectos de AFB1 sobre GSH, lo cual sugiere que ambas sustancias pudieran conferir un efecto protector de las aves

  4. Induction of CYP1A1, CYP1A2, and CYP1B1 mRNAs by nitropolycyclic aromatic hydrocarbons in various human tissue-derived cells: chemical-, cytochrome P450 isoform-, and cell-specific differences

    Energy Technology Data Exchange (ETDEWEB)

    Iwanari, M.; Nakajima, M.; Yokoi, T. [Div. of Drug Metabolism, Kanazawa Univ., Kanazawa (Japan); Kizu, R.; Hayakawa, K. [Lab. of Hygienic Chemistry, Kanazawa Univ., Kanazawa (Japan)

    2002-06-01

    Nitropolycyclic aromatic hydrocarbons (NPAHs) are found in diesel exhaust and ambient air. NPAHs as well as polycyclic aromatic hydrocarbons (PAHs) are known to have mutagenicity, carcinogenicity, and endocrine-disruptive effects. In the present study, the inducibility of the human cytochrome P450-1 (CYP1) family by NPAHs was compared with those produced by their parent PAHs and some reductive metabolites, amino-PAHs. Furthermore, to investigate the differences in the inducibility of the CYP1 family in human tissues, various human tissue-derived cell lines, namely HepG2 (hepatocellular carcinoma), ACHN (renal carcinoma), A549 (lung carcinoma), MCF-7 (breast carcinoma), LS-180 (colon carcinoma), HT-1197 (bladder carcinoma), HeLa (cervix of uterus adenocarcinoma), OMC-3 (ovarian carcinoma), and NEC14 (testis embryonal carcinoma), were treated with NPAHs, PAHs, or amino-PAHs. The mRNA levels of CYP1A1, CYP1A2, and CYP1B1 were determined with reverse transcription-polymerase chain reaction (RT-PCR). The cell lines were classified into two groups: CYP1 inducible cell lines, comprising HepG2, MCF-7, LS-180, and OMC-3 cells, and CYP1 non-inducible cell lines, comprising ACHN, A549, HT-1197, HeLa, and NEC14 cells. In inducible cell lines, the induction profile of chemical specificity was similar for CYP1A1, CYP1A2, and CYP1B1, although the extent of induction differed among the cell lines and for the CYP isoforms. Pyrene, 1-nitropyrene, 1-aminopyrene, 1,3-, 1,6-, and 1,8-dinitropyrenes slightly induced CYP1 mRNAs, but 1,3-dinitropyrene produced a 6-fold induction of CYP1A1 mRNA in MCF-7 cells. 2-Nitrofluoranthene and 3-nitrofluoranthene exhibited stronger inducibility than fluoranthene in the inducible cell lines. 6-Nitrochrysene induced CYP1 mRNAs to the same extent or more potently than chrysene. The induction potencies of 6-nitrobenzo[a]pyrene and 7-nitrobenz[a]anthracene were weaker than those of their parents benzo[a]pyrene and benz[a]anthracene, respectively. This

  5. Kinin B1 Receptor Promotes Neurogenic Hypertension Through Activation of Centrally Mediated Mechanisms.

    Science.gov (United States)

    Sriramula, Srinivas; Lazartigues, Eric

    2017-12-01

    Hypertension is associated with increased activity of the kallikrein-kinin system. Kinin B1 receptor (B1R) activation leads to vasoconstriction and inflammation. Despite evidence supporting a role for the B1R in blood pressure regulation, the mechanisms by which B1R could alter autonomic function and participate in the pathogenesis of hypertension remain unidentified. We sought to explore whether B1R-mediated inflammation contributes to hypertension and investigate the molecular mechanisms involved. In this study, we tested the hypothesis that activation of B1R in the brain is involved in the pathogenesis of hypertension, using the deoxycorticosterone acetate-salt model of neurogenic hypertension in wild-type and B1R knockout mice. Deoxycorticosterone acetate-salt treatment in wild-type mice led to significant increases in B1R mRNA and protein levels and bradykinin levels, enhanced gene expression of carboxypeptidase N supporting an increase in the B1R ligand, associated with enhanced blood pressure, inflammation, sympathoexcitation, autonomic dysfunction, and impaired baroreflex sensitivity, whereas these changes were blunted or prevented in B1R knockout mice. B1R stimulation was further shown to involve activation of the ASK1-JNK-ERK1/2 and NF-κB pathways in the brain. To dismiss potential developmental alterations in knockout mice, we further used B1R blockade selectively in the brain of wild-type mice. Supporting the central origin of this mechanism, intracerebroventricular infusion of a specific B1R antagonist, attenuated the deoxycorticosterone acetate-salt-induced increase in blood pressure in wild-type mice. Our data provide the first evidence of a central role for B1R-mediated inflammatory pathways in the pathogenesis of deoxycorticosterone acetate-salt hypertension and offer novel insights into possible B1R-targeted therapies for the treatment of neurogenic hypertension. © 2017 American Heart Association, Inc.

  6. The link between high-fat meals and postprandial activation of blood coagulation factor VII possibly involves kallikrein

    DEFF Research Database (Denmark)

    Larsen, L F; Marckmann, P; Bladbjerg, Else-Marie

    2000-01-01

    Contrary to low-fat meals, high-fat meals are known to cause postprandial factor VII (FVII) activation, but the mechanism is unknown. To study the postprandial FVII activation in detail, 18 young men consumed in randomized order high-fat or low-fat test meals. Fasting and non-fasting blood samples...... that triglyceride-rich lipoproteins may activate prokallikrein. Neither plasma triglycerides nor kallikrein and activated FVII were statistically associated. This may suggest that additional factors are involved in the postprandial FVII activation. No clear evidence for a role of tissue factor expression...... by monocytes, factor XII or insulin in postprandial FVII activation was observed. Tissue factor pathway inhibitor and prothrombin fragment 1+2, a marker of thrombin generation, were not affected postprandially after either the high-fat or the low-fat meals. Our findings indicate that triglyceride...

  7. Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer

    Science.gov (United States)

    Zheng, Jun; Zhang, Ding; Liu, Wei; Zheng, Wei Hong; Li, Xiao Song; Yao, Ru Cheng; Wang, Fangyu; Liu, Sen; Tan, Xiao

    2018-01-01

    Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease. PMID:29560118

  8. Activation of Membrane-Bound Kallikrein and Renin in the Kidney.

    Science.gov (United States)

    1980-05-23

    included repeated washings with hypotonic buffer. Kallikrein activity in the PM fraction (PM-kallikrein) averaged 1.81 nmol of S-2266 hydrolyzed per min...thousand Fig. 1 times more active than lysolecithin on a molar basis. Lecithin and arachidonic acid were active only at a much higher concentration...taglandin E2 (11), arachidonic acid or lecithin . However, melittin, on a molar basis, was about three orders of magnitude more potent than

  9. Excess antibody immunoassays for rat glandular kallikreins. Measurement of kallikrein from different organs in the presence of cross-reacting antigens

    International Nuclear Information System (INIS)

    Johansen, L.; Oerstavik, T.B.; Holck, M.; Nustad, K.

    1983-01-01

    An immunoradiometric assay has previously been developed for measurement of rat glandular kallikrein. In the present paper, further studies on the specificity and sensitivity of the method are described. Problems of interference of immunologically cross-reacting antigens were overcome by proper preabsorption of the antibody. A method was thus established in which enzymatic activity of the immunoreactive kallikrein could be measured even in the presence of enzymes sharing immunological determinants and substrate specificity with kallikrein. Two variants of the immunoradiometric assay have been evaluated. A simplified version with simultaneous addition of all reagents gave results equal to those obtained in the original assay. A further modification with delayed addition of the solid-phase antibody, gave considerable improvement in assay sensitivity. (Auth.)

  10. Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

    Directory of Open Access Journals (Sweden)

    Gozzo A.J.

    2003-01-01

    Full Text Available Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates reduced (1.2 to 3.0 times the catalytic efficiency of kallikrein (in a nanomolar range on the hydrolysis of plasminogen (0.3 to 1.8 µM and increased (1.9 to 7.7 times the enzyme efficiency in factor XII (0.1 to 10 µM activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times kallikrein inhibition by antithrombin (1.4 µM, while chondroitin 4- and 6-sulfates reduced it (1.3 times. Heparin and heparan sulfate increased (1.4 times the enzyme inhibition by the C1-inhibitor (150 nM.

  11. Development of a UPLC-FLD Method for Detection of Aflatoxin B1 and M1 in Animal Tissue to Study the Effect of Curcumin on Mycotoxin Clearance Rates

    Directory of Open Access Journals (Sweden)

    Xiaoxu Cui

    2017-09-01

    Full Text Available Aflatoxin B1 (AFB1 and its metabolite aflatoxin M1 (AFM1 are well-known carcinogens for humans and animals health. In this study, an ultra-high performance liquid chromatography linked with fluorescence detection (UPLC-FLD method was optimized and validated. In addition, we investigated for the first time, the influence of curcumin on residue depletion of AFB1 and AFM1 in liver, kidney, and muscle tissues of broiler chickens and estimated a necessary clearance time required for AFB1 and AFM1 residues. The results showed that the average recoveries of AFB1 varied in liver, kidney, and muscles between 82.32–85.56, 85.34–88.45, and 84.88–89.73% respectively, while the average recoveries of AFM1 in liver, kidney, and muscles varied between 92.17–95.03, 94.12–97.21, and 95.32–98.51%, respectively. The detection limit of aflatoxin B1 was 0.008 ng/ml, while for aflatoxin M1 was 0.003 ng/ml. The limit of quantification (LOQ for AFB1 and AFM1 was 0.02 and 0.01 ng/ml, respectively. Clearance time for AFB1 and AFM1 residues were analyzed in two experimental groups of broilers. One group fed with dietary AFB1 (5.0 mg/kg feed and other with curcumin+AFB1 diet (curcumin; 300 mg/kg feed, AFB1; 5.0 mg/kg feed. AFB1 and AFM1 residues clearance time was calculated based on LOQ using withdrawal time calculation software (WT1.4. Clearance time analyzed for AFB1 ranged from 11 to 19 days and for AFM1 ranged from 10 to 12 days at 95% confidence level. Interestingly, curcumin supplementation in the diet reduced the clearance time of AFM1 in liver and kidney but not in muscle tissues. Conclusively, the developed method can be appropriately used for the quality control testing of commercial broiler-meat processing companies, food manufacturers, and quality control laboratories.

  12. 3H-thymidine autoradiographic study of cell proliferation and the influence of isoproterenol and kallikrein in various cell populations of the gastrointestinal tract in animal experiments

    International Nuclear Information System (INIS)

    Albrecht, S.

    1981-01-01

    Morphological studies were carried out with the aim of studying cell proliferation in various tissues (stable and epithelial tissues) of the gastrointestinal tract. The cells were studied by 3 H thymidine autoradiography in the normal age cycle and under the influence of kallikrein or isoproterenol. Epithelial cells and smooth muscle cells of the forestomach, stomach, small intestine and colon were investigated and, in the case of the stomach, also connective-tissue cells of the mucotic stroma. Counts across the total epithelial thickness yielded similar results for the oesophagus and the forestomach. A count of 1000 cells per animal was found to yield representative information on a defined type of cell. Kallikrein was not found to have a constant mitosis-promoting effect. Isoproterenol caused the labelling index to increase or to decrease; in higher concentrations, it increased the proliferation rate in all cell types. In male animals, the labelling indices of connective-tissue cells of the gastric mucosa were significantly higher than in female animals. (orig./MG) [de

  13. Transcriptome reveals the overexpression of a kallikrein gene cluster (KLK1/3/7/8/12) in the Tibetans with high altitude-associated polycythemia.

    Science.gov (United States)

    Li, Kang; Gesang, Luobu; Dan, Zeng; Gusang, Lamu

    2017-02-01

    High altitude-associated polycythemia (HAPC) is a very common disease. However, it the disease is still unmanageable and the related molecular mechanisms remain largely unclear. In the present study, we aimed to explore the molecular mechanisms responsible for the development of HAPC using transcriptome analysis. Transcriptome analysis was conducted in 3 pairs of gastric mucosa tissues from patients with HAPC and healthy residents at a similar altitude. Endoscopy and histopathological analyses were used to examine the injury to gastric tissues. Molecular remodeling was performed for the interaction between different KLK members and cholesterol. HAPC was found to lead to morphological changes and pathological damage to the gastric mucosa of patients. A total of 10,304 differentially expressed genes (DEGs) were identified. Among these genes, 4,941 DEGs were upregulated, while 5,363 DEGs were downregulated in the patients with HAPC (fold change ≥2, P17-fold. All the members had high-score binding cholesterol, particularly for the polymers of KLK7. The kallikrein gene cluster (KLK1/3/7/8/12) is on chromosome 19q13.3-13.4. The elevated levels of KLK1, KLK3, KLK7, KLK8 and KLK12 may be closely associated with the hypertension, inflammation, obesity and other gastric injuries associated with polycythemia. The interaction of KLKs and cholesterol maybe play an important role in the development of hypertension. The findings of the present study revealed that HAPC induces gastric injury by upregulating the kallikrein gene cluster (KLK1/3/7/8/12), which can bind cholesterol and result in kallikrein hypertension. These findings provide some basic information for understanding the molecular mechanisms responsible for HAPC and HAPC-related diseases.

  14. Characterization of kallikrein-related peptidase 4 glycosylations.

    Science.gov (United States)

    Yamakoshi, Yasuo; Yamakoshi, Fumiko; Hu, Jan C-C; Simmer, James P

    2011-12-01

    Kallikrein-related peptidase 4 (KLK4) is a glycosylated serine protease that functions in the maturation (hardening) of dental enamel. Pig and mouse KLK4 contain three potential N-glycosylation sites. We isolated KLK4 from developing pig and mouse molars and characterized their N-glycosylations. N-glycans were enzymatically released by digestion with N-glycosidase F and fluorescently labeled with 2-aminobenzoic acid. Normal-phase high-performance liquid chromatography (NP-HPLC) revealed N-glycans with no, or with one, two, or three sialic acid attachments in pig KLK4 and with no, or with one or two sialic acid attachments in mouse KLK4. The labeled N-glycans were digested with sialidase to generate the asialo N-glycan cores that were fractionated by reverse-phase HPLC, and their retention times were compared with similarly labeled glycan standards. The purified cores were characterized by mass spectrometric and monosaccharide composition analyses. We determined that pig and mouse KLK4 have NA2 and NA2F biantennary N-glycan cores. The pig triantennary core is NA3. The mouse triantennary core is NA3 with a fucose connected by an α1-6 linkage, indicating that it is attached to the first N-acetyglucosamine (NA3F). We conclude that pig KLK4 has NA2, NA2F, and NA3 N-glycan cores with no, or with one, two, or three sialic acids. Mouse KLK4 has NA2, NA2F, and NA3F N-glycan cores with no, or with one or two sialic acids. © 2011 Eur J Oral Sci.

  15. Radioimmunoassay of glandular kallikrein in human plasma after partial purification by immunoaffinity column

    International Nuclear Information System (INIS)

    Nishimura, Kazutaka; Inoue, Yoshikazu; Kokubu, Tatsuo

    1987-01-01

    Glandular kallikrein in human plasma was partially purified by immunoaffinity column and was measured by a radioimmunoassay (RIA). Plasma was diluted with an equal volume of 10 mmol/l sodium phosphate buffer, pH 7.4, containing 0.9% NaCl (PBS) and was applied to an immunoaffinity column from which glandular kallikrein was eluted with 3 mol/l NaSCN (20 ml). The enzymic fraction was concentrated with an Amicon PM 10 filter and dialyzed against PBS. The final recovery of the enzyme was 51.6 ± 1.6%, determined by using [ 125 I]kallikrein. The usable range of the standard curve covered 2.5-100 ng/tube. The coefficient of variation within the series was 5.9%, and the coefficient of variation between the series was 7.6%. In healthy controls, the plasma content of glandular kallikrein was 1.36 ± 0.39 ng/ml. In patients with acute pancreatitis, the plasma concentration was 8.02 ± 6.15 ng/ml, significantly different from the control group. (Auth.)

  16. Arginine-esterase activity of kallikrein in the sera of whole-body irradiated rats and guinea-pigs

    Energy Technology Data Exchange (ETDEWEB)

    Pouckova, P; Pospisil, J; Dienstbier, Z [Karlova Univ., Prague (Czechoslovakia). Biofyzikalni Ustav

    1977-09-01

    In whole-body irradiated rats (800 R=LDsub(50/30)) and guinea pigs (300 R=LDsub(50/30)) changes were investigated in the arginine esterase activity of kallikrein in native serum as well as in serum exposed to contact with a clay suspension. From the values obtained the activity of prekallikrein was calculated. While in the rat serum significant changes in the arginine esterase activity of kallikrein were found, in the guinea pig serum the kallikrein activity did not change markedly. The activity of prekallikrein immediately after irradiation assumes a similar course in both types of laboratory animals while during later intervals a reverse pattern was observed.

  17. Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan Sulfate Proteoglycans

    Directory of Open Access Journals (Sweden)

    Guacyara Motta

    2017-07-01

    Full Text Available Human plasma kallikrein-kinin system proteins are related to inflammation through bradykinin. In the proximity of its target cells, high molecular weight kininogen (H-kininogen is the substrate of plasma kallikrein, which releases bradykinin from H-kininogen. Heparan sulfate proteoglycans (HSPGs play a critical role in either recruiting kinin precursors from the plasma, or in the assembly of kallikrein-kinin system components on the cell surface. Furthermore, HSPGs mediate the endocytosis and activation of H-kininogen and plasma prekallikrein. In the presence of HSPGs (Chinese hamster ovary cell, CHO-K1, wild type cells both heparin and heparan sulfate strongly inhibit the H-kininogen interaction with the cell membrane. H-kininogen is internalized in endosomal acidic vesicles in CHO-K1 but not in CHO-745 cells (mutant cells deficient in glycosaminoglycan biosynthesis. The endocytosis process is lipid raft-mediated and is dependent on caveolae. Both types of CHO cells do not internalize bradykinin-free H-kininogen. At pH 7.35, bradykinin is released from H-kininogen on the surface of CHO-745 cells only by serine proteases; however, in CHO-K1 cells either serine or cysteine proteases are found to be involved. The CHO-K1 cell lysate contains different kininogenases. Plasma prekallikrein endocytosis in CHO-K1 cells is independent of H-kininogen, and also prekallikrein is not internalized by CHO-745 cells. Plasma prekallikrein cleavage/activation is independent of glycosaminoglycans but plasma kallikrein formation is more specific on H-kininogen assembled on the cell surface through glycosaminoglycans. In this mini-review, the importance of HSPGs in the regulation of plasma kallikrein-kinin system proteins is shown.

  18. The Kallikrein-Kinin System in Bartter's Syndrome and Its Response to Prostaglandin Synthetase Inhibition

    Science.gov (United States)

    Vinci, Joseph M.; Gill, John R.; Bowden, Robert E.; Pisano, John J.; Izzo, Joseph L.; Radfar, Nazam; Taylor, Addison A.; Zusman, Randall M.; Bartter, Frederic C.; Keiser, Harry R.

    1978-01-01

    The kallikrein-kinin system was characterized in seven patients with Bartter's syndrome on constant metabolic regimens before, during, and after treatment with prostaglandin synthetase inhibitors. Patients with Bartter's syndrome had high values for plasma bradykinin, plasma renin activity (PRA), urinary kallikrein, urinary immunoreactive prostaglandin E excretion, and urinary aldosterone; urinary kinins were subnormal and plasma prekallikrein was normal. Treatment with indomethacin or ibuprofen which decreased urinary immunoreactive prostaglandin E excretion by 67%, decreased mean PRA (patients recumbent) from 17.3±5.3 (S.E.M.) ng/ml per h to 3.3±1.1 ng/ml per h, mean plasma bradykinin (patients recumbent) from 15.4±4.4 ng/ml to 3.9±0.9 ng/ml, mean urinary kallikrein excretion from 24.8±3.2 tosyl-arginine-methyl ester units (TU)/day to 12.4±2.0 TU/day, but increased mean urinary kinin excretion from 3.8±1.3 μg/day to 8.5±2.5 μg/day. Plasma prekallikrein remained unchanged at 1.4 TU/ml. Thus, with prostaglandin synthetase inhibition, values for urinary kallikrein and kinin and plasma bradykinin returned to normal pari passu with changes in PRA, in aldosterone, and in prostaglandin E. The results suggest that, in Bartter's syndrome, prostaglandins mediate the low urinary kinins and the high plasma bradykinin, and that urinary kallikrein, which is aldosterone dependent, does not control kinin excretion. The high plasma bradykinin may be a cause of the pressor hyporesponsiveness to angiotensin II which characterizes the syndrome. PMID:96139

  19. Rhodium. Suppl. Vol. B1

    International Nuclear Information System (INIS)

    Griffith, W.P.; Jehn, H.; McCleverty, J.A.; Raub, C.J.; Robinson, S.D.

    1982-01-01

    The present rhodium vol. B1 is concerned largely with linary compounds and coordination complexes of this important metal, which is used either alone or in alloy form for fabrication of other materials or for heterogeneous catalysis. In first two chapters are devoted for hydrides, oxides, ternary and quaternary oxorhodates. Third chapter is on different type of complexes with nitrogen. From chapter four to seven is on halogen complexes with this metal. Next chapters are on sulphides, sulphoxide and sulphito complexes, sulphates and sulphato complexes, selenides and tellurides, borides, borane complexes, carbides, carbonato, cyno, fulminato and thiocyanato complexes. Finally, silicide, phosphides, phosphito and arsenides are treated over here. (AB)

  20. Desmoglein 2 is a substrate of kallikrein 7 in pancreatic cancer

    International Nuclear Information System (INIS)

    Ramani, Vishnu C; Hennings, Leah; Haun, Randy S

    2008-01-01

    In a previous report we have demonstrated that the chymotryptic-like serine protease kallikrein 7 (KLK7/hK7) is overexpressed in pancreatic cancer. In normal skin, hK7 is thought to participate in skin desquamation by contributing in the degradation of desmosomal components, such as desmogleins. Thus, the ability of hK7 to degrade desmogleins was assessed and the effect of hK7 expression on desmoglein 2 was examined in cultured pancreatic cancer cells. The expression of Dsg1, Dsg2, and Dsg3 in pancreatic tissues was examined by immunohistochemistry and their expression in two pancreatic cancer cell lines, BxPC-3 and Panc-1, was determined by western blot analysis. The ability of hK7 to degrade Dsg1 and Dsg2 was investigated using in vitro degradation assays. BxPC-3 cells stably transfected to overexpress hK7 were used to examine the effect of hK7 on cell-surface resident Dsg2. The levels of immunoreactive Dsg1 and Dsg2 were reduced in pancreatic adenocarcinomas compared with both normal pancreatic and chronic pancreatitis tissues. Among the desmosomal proteins examined, Dsg2 exhibited robust expression on the surface of BxPC-3 cells. When hK7 was overexpressed in this cell line, there was a significant increase in the amount of soluble Dsg2 released into the culture medium compared with vector-transfected control cells. A reduction in the amount of the cell adhesion components Dsg1 and Dsg2 in pancreatic tumors suggests that loss of these desmosomal proteins may play a role in pancreatic cancer invasion. Using in vitro degradation assays, both Dsg1 and Dsg2 could be readily proteolyzed by hK7, which is overexpressed in pancreatic adenocarcinomas. The enforced expression of hK7 in BxPC-3 cells that express significant amounts of Dsg2 resulted in a marked increase in the shedding of soluble Dsg2, which is consistent with the notion that aberrant expression of hK7 in pancreatic tumors may result in diminished cell-cell adhesion and facilitate tumor cell invasion

  1. Plasma kallikrein enhances platelet aggregation response by subthreshold doses of ADP.

    Science.gov (United States)

    Ottaiano, Tatiana F; Andrade, Sheila S; de Oliveira, Cleide; Silva, Mariana C C; Buri, Marcus V; Juliano, Maria A; Girão, Manoel J B C; Sampaio, Misako U; Schmaier, Alvin H; Wlodawer, Alexander; Maffei, Francisco H A; Oliva, Maria Luiza V

    2017-04-01

    Human plasma kallikrein (huPK) potentiates platelet responses to subthreshold doses of ADP, although huPK itself, does not induce platelet aggregation. In the present investigation, we observe that huPK pretreatment of platelets potentiates ADP-induced platelet activation by prior proteolysis of the G-protein-coupled receptor PAR-1. The potentiation of ADP-induced platelet activation by huPK is mediated by the integrin α IIb β 3 through interactions with the KGD/KGE sequence motif in huPK. Integrin α IIb β 3 is a cofactor for huPK binding to platelets to support PAR-1 hydrolysis that contributes to activation of the ADP signaling pathway. This activation pathway leads to phosphorylation of Src, AktS 473 , ERK1/2, and p38 MAPK, and to Ca 2+ release. The effect of huPK is blocked by specific antagonists of PAR-1 (SCH 19197) and α IIb β 3 (abciximab) and by synthetic peptides comprising the KGD and KGE sequence motifs of huPK. Further, recombinant plasma kallikrein inhibitor, rBbKI, also blocks this entire mechanism. These results suggest a new function for huPK. Formation of plasma kallikrein lowers the threshold for ADP-induced platelet activation. The present observations are consistent with the notion that plasma kallikrein promotes vascular disease and thrombosis in the intravascular compartment and its inhibition may ameliorate cardiovascular disease and thrombosis. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  2. An interaction of renin-angiotensin and kallikrein-kinin systems contributes to vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro studies.

    Directory of Open Access Journals (Sweden)

    Graziela S Ceravolo

    Full Text Available The kallikrein-kinin and renin-angiotensin systems interact at multiple levels. In the present study, we tested the hypothesis that the B1 kinin receptor (B1R contributes to vascular hypertrophy in angiotensin II (ANG II-induced hypertension, through a mechanism involving reactive oxygen species (ROS generation and extracellular signal-regulated kinase (ERK1/2 activation. Male Wistar rats were infused with vehicle (control rats, 400 ng/Kg/min ANG II (ANG II rats or 400 ng/Kg/min ANG II plus B1 receptor antagonist, 350 ng/Kg/min des-Arg(9-Leu(8-bradykinin (ANGII+DAL rats, via osmotic mini-pumps (14 days or received ANG II plus losartan (10 mg/Kg, 14 days, gavage - ANG II+LOS rats. After 14 days, ANG II rats exhibited increased systolic arterial pressure [(mmHg 184 ± 5.9 vs 115 ± 2.3], aortic hypertrophy; increased ROS generation [2-hydroxyethidium/dihydroethidium (EOH/DHE: 21.8 ± 2.7 vs 6.0 ± 1.8] and ERK1/2 phosphorylation (% of control: 218.3 ± 29.4 vs 100 ± 0.25]. B1R expression was increased in aortas from ANG II and ANG II+DAL rats than in aortas from the ANG II+LOS and control groups. B1R antagonism reduced aorta hypertrophy, prevented ROS generation (EOH/DHE: 9.17 ± 3.1 and ERK1/2 phosphorylation (137 ± 20.7% in ANG II rats. Cultured aortic vascular smooth muscle cells (VSMC stimulated with low concentrations (0.1 nM of ANG II plus B1R agonist exhibited increased ROS generation, ERK1/2 phosphorylation, proliferating-cell nuclear antigen expression and [H3]leucine incorporation. At this concentration, neither ANG II nor the B1R agonist produced any effects when tested individually. The ANG II/B1R agonist synergism was inhibited by losartan (AT1 blocker, 10 µM, B1R antagonist (10 µM and Tiron (superoxide anion scavenger, 10 mM. These data suggest that B1R activation contributes to ANG II-induced aortic hypertrophy. This is associated with activation of redox-regulated ERK1/2 pathway that controls aortic smooth muscle cells growth

  3. Effect of an esterified glucomannan on laying hens exposed to combined mycotoxins (aflatoxin B1, zearalenone and fumonisin B1)

    OpenAIRE

    A. Zaghini; A. Altafini; M. Simioli; L. Rizzi

    2011-01-01

    Mycotoxin toxicity depends on species, exposure time, age, sex, health and possible synergistic effects of other mycotoxins present in feed. In poultry, aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are associated with poor growth performance, lowered feed utilization efficiency, liver damage and immunosuppression; metabolites may persist in tissues and eggs. Exposure of mature hens to zearalenone (ZEN) apparently does not cause adverse effects, but ZEN residues and α and β zearalenol...

  4. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis

    OpenAIRE

    Ren, Decheng; Zhou, Yingjiang; Morris, David; Li, Minghua; Li, Zhiqin; Rui, Liangyou

    2007-01-01

    SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (α, β, γ, and/or δ) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1β was specifically expressed in neural tissue in SH2B1-tran...

  5. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis.

    Science.gov (United States)

    Ren, Decheng; Zhou, Yingjiang; Morris, David; Li, Minghua; Li, Zhiqin; Rui, Liangyou

    2007-02-01

    SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (alpha, beta, gamma, and/or delta) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1beta was specifically expressed in neural tissue in SH2B1-transgenic (SH2B1(Tg)) mice. SH2B1(Tg) mice were crossed with SH2B1-knockout (SH2B1(KO)) mice to generate SH2B1(TgKO) mice expressing SH2B1 only in neural tissue but not in other tissues. Systemic deletion of the SH2B1 gene resulted in metabolic disorders in SH2B1(KO) mice, including hyperlipidemia, leptin resistance, hyperphagia, obesity, hyperglycemia, insulin resistance, and glucose intolerance. Neuron-specific restoration of SH2B1beta not only corrected the metabolic disorders in SH2B1(TgKO) mice, but also improved JAK2-mediated leptin signaling and leptin regulation of orexigenic neuropeptide expression in the hypothalamus. Moreover, neuron-specific overexpression of SH2B1 dose-dependently protected against high-fat diet-induced leptin resistance and obesity. These observations suggest that neuronal SH2B1 regulates energy balance, body weight, peripheral insulin sensitivity, and glucose homeostasis at least in part by enhancing hypothalamic leptin sensitivity.

  6. 34 CFR 5b.1 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... maintained by the Department, including but not limited to the individual's education, financial transactions... 34 Education 1 2010-07-01 2010-07-01 false Definitions. 5b.1 Section 5b.1 Education Office of the Secretary, Department of Education PRIVACY ACT REGULATIONS § 5b.1 Definitions. As used in this part: (a...

  7. 7 CFR 15b.1 - Purpose.

    Science.gov (United States)

    2010-01-01

    ... FEDERAL FINANCIAL ASSISTANCE General Provisions § 15b.1 Purpose. The purpose of this part is to implement... 7 Agriculture 1 2010-01-01 2010-01-01 false Purpose. 15b.1 Section 15b.1 Agriculture Office of the... receiving Federal financial assistance. ...

  8. 15 CFR 8b.1 - Purpose.

    Science.gov (United States)

    2010-01-01

    ... of handicap in any program or activity receiving Federal financial assistance. The purpose of this... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Purpose. 8b.1 Section 8b.1 Commerce... HANDICAPPED IN FEDERALLY ASSISTED PROGRAMS OPERATED BY THE DEPARTMENT OF COMMERCE General Provisions § 8b.1...

  9. Expression and localization of tissue factor pathway inhibitor-2 in normal and atherosclerotic human vessels

    NARCIS (Netherlands)

    Crawley, James T. B.; Goulding, David A.; Ferreira, Valérie; Severs, Nicholas J.; Lupu, Florea

    2002-01-01

    Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type, serine protease inhibitor with inhibitory activity toward activated factor XI, plasma kallikrein, plasmin, certain matrix metalloproteinases, and the tissue factor:activated factor VII complex. In this study, we investigated TFPI-2

  10. A study on the possibility of production of aflatoxin B1 in saffron

    Directory of Open Access Journals (Sweden)

    Abbas Mohammadi

    2017-06-01

    Full Text Available Saffron is the most important medicinal plants in the Khorasan Razavi and South Khorasan provinces, Iran. Aspergillus species can infect saffron tissues during harvesting, storage and transportation. Aflatoxin B1 is one of the important carcinogenic mycotoxin which is produced by Aspergillus species in saffron tissues. This study was carried out in order to investigate the production of aflatoxin B1 in saffron tissues from farm to food by TLC chromatography during the year 2015. Wet and dry saffron tissues and rice grains (with and without saffron extract were inoculated with Aspergillus flavus spore suspensions. Production of Aflatoxin B1 in inoculated tissues was investigated by the TLC chromatography method. The results showed that the wet leaves and rice grains were infected with Aspergillus species very quickly. However, this process was very slow in dry tissues. Aflatoxin B1 was detected in all of the tested samples. The amounts of Aflatoxin B1 in the wet saffron tissues and rice grains were more than those found in dry tissues and saffron rice, respectively. The amount of Aflatoxin B1 had a direct correlation with moisture in the environment and the tissues. The contamination of the tissues and production of AflatoxinB1 were increased with increasing the amount of moisture. The results showed that the packaging of saffron before complete drying of its tissue or storing it in conditions with high humidity can increase the risk of infection with the Aspergillus species and production of Aflatoxin B1 in them. Based on our data, saffron can reduce Aspergillus infection and aflatoxin B1 production but not inhibit it. Saffron extract reduces Aspergillus infection and Aflatoxin B1 production in food and grains.

  11. 45 CFR 73b.1 - Scope.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Scope. 73b.1 Section 73b.1 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION DEBARMENT OR SUSPENSION OF FORMER EMPLOYEES... officer or employee of the Department, including former and retired officers of the commissioned corps of...

  12. Study of the components of renin-angiotensinaldosterone system and KalliKrein -Kinin system in normal pregnancy

    International Nuclear Information System (INIS)

    Abreu Fagundes, V.G. de.

    1984-01-01

    The alterations in the renin-angiotensin-aldosterone system and Kallikrein-Kinin system were studied. The possible interferences of these systems on the arterial pressure and on the evolution of normal pregnancy were presented in the following situations: when the pregnant change from dorsal decumbency to left lateral decumbency and to orthostatic position. (M.A.C.) [pt

  13. Renal Kallikrein Activation and Renoprotection after Dual Blockade of Renin-Angiotensin System in Diet-Induced Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Xia Zou

    2015-01-01

    Full Text Available Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN. Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF- β and α-smooth muscle action (SMA. Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P<0.05. Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response.

  14. Reactivity of alpha 1-antitrypsin mutants against proteolytic enzymes of the kallikrein-kinin, complement, and fibrinolytic systems

    NARCIS (Netherlands)

    Patston, P.A.; Roodi, N.; Schifferli, J.A.; Bischoff, Rainer; Courtney, M.; Schapira, M.

    1990-01-01

    Increased extracellular proteolysis because of unregulated activation of blood coagulation, complement, and fibrinolysis is observed in thrombosis, shock, and inflammation. In the present study, we have examined whether the plasma kallikrein-kinin system, the classical pathway of complement, and the

  15. CYP1B1 expression, a potential risk factor for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Erdmann, Christine A.; Russell, Marion

    2001-05-31

    CYP1B1 expression in non-tumor breast tissue from breast cancer patients and cancer-free individuals was determined to test the hypothesis that high CYP1B1 expression is a risk factor for breast cancer. Large interindividual variations in CYP1B1 expression were found with CYP1B1 levels notably higher in breast cancer patients than cancer-free individuals. The results indicate that CYP1B1 might play a role in breast cancer either through increased PAH activation or through metabolism of endogenous estrogen to a carcinogenic derivative.

  16. MR fingerprinting with simultaneous B1 estimation.

    Science.gov (United States)

    Buonincontri, Guido; Sawiak, Stephen J

    2016-10-01

    MR fingerprinting (MRF) can be used for quantitative estimation of physical parameters in MRI. Here, we extend the method to incorporate B1 estimation. The acquisition is based on steady state free precession MR fingerprinting with a Cartesian trajectory. To increase the sensitivity to the B1 profile, abrupt changes in flip angle were introduced in the sequence. Slice profile and B1 effects were included in the dictionary and the results from two- and three-dimensional (3D) acquisitions were compared. Acceleration was demonstrated using retrospective undersampling in the phase encode directions of 3D data exploiting redundancy between MRF frames at the edges of k-space. Without B1 estimation, T2 and B1 were inaccurate by more than 20%. Abrupt changes in flip angle improved B1 maps. T1 and T2 values obtained with the new MRF methods agree with classical spin echo measurements and are independent of the B1 field profile. When using view sharing reconstruction, results remained accurate (error Reson Med 76:1127-1135, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  17. Improving virtual screening predictive accuracy of Human kallikrein 5 inhibitors using machine learning models.

    Science.gov (United States)

    Fang, Xingang; Bagui, Sikha; Bagui, Subhash

    2017-08-01

    The readily available high throughput screening (HTS) data from the PubChem database provides an opportunity for mining of small molecules in a variety of biological systems using machine learning techniques. From the thousands of available molecular descriptors developed to encode useful chemical information representing the characteristics of molecules, descriptor selection is an essential step in building an optimal quantitative structural-activity relationship (QSAR) model. For the development of a systematic descriptor selection strategy, we need the understanding of the relationship between: (i) the descriptor selection; (ii) the choice of the machine learning model; and (iii) the characteristics of the target bio-molecule. In this work, we employed the Signature descriptor to generate a dataset on the Human kallikrein 5 (hK 5) inhibition confirmatory assay data and compared multiple classification models including logistic regression, support vector machine, random forest and k-nearest neighbor. Under optimal conditions, the logistic regression model provided extremely high overall accuracy (98%) and precision (90%), with good sensitivity (65%) in the cross validation test. In testing the primary HTS screening data with more than 200K molecular structures, the logistic regression model exhibited the capability of eliminating more than 99.9% of the inactive structures. As part of our exploration of the descriptor-model-target relationship, the excellent predictive performance of the combination of the Signature descriptor and the logistic regression model on the assay data of the Human kallikrein 5 (hK 5) target suggested a feasible descriptor/model selection strategy on similar targets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Tissue

    Directory of Open Access Journals (Sweden)

    David Morrissey

    2012-01-01

    Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

  19. Effect of pancreatic kallikrein combined with magnesium sulfate therapy on disease severity of patients with severe preeclampsia

    Directory of Open Access Journals (Sweden)

    Yi Yang

    2016-10-01

    Full Text Available Objective: To study the clinical effect of pancreatic kallikrein combined with magnesium sulfate therapy on severe preeclampsia. Methods: A total of 47 patients with severe preeclampsia treated in our hospital from May 2013 to October 2015 were retrospectively analyzed, patients who received pancreatic kallikrein combined with magnesium sulfate therapy were selected as observation group, patients who received magnesium sulfate therapy were selected as control group, and then blood pressure level, renal function, uterine artery and umbilical artery blood flow state, and hypoxia indexes in serum and placenta were compared between two groups. Results: After treatment, systolic pressure and diastolic pressure levels as well as serum CysC level and 24 h urine protein level of observation group were significantly lower than those of control group, the uterine artery and umbilical artery S/ D and PI were significantly lower than those of control group, PIGF and NO levels in serum as well as Xiap and Survivin levels in placenta were significantly higher than those of control group, and sVEGFR1 level in serum as well as Caspase-3 and Caspase-7 levels in placenta was significantly lower than those of control group. Conclusions: Pancreatic kallikrein combined with magnesium sulfate therapy can alleviate the disease severity, lower blood pressure and vascular resistance, and improve renal function and the apoptosis caused by placental hypoxia in patients with severe preeclampsia.

  20. The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models.

    Science.gov (United States)

    Brito, Marlon V; de Oliveira, Cleide; Salu, Bruno R; Andrade, Sonia A; Malloy, Paula M D; Sato, Ana C; Vicente, Cristina P; Sampaio, Misako U; Maffei, Francisco H A; Oliva, Maria Luiza V

    2014-05-01

    The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Imbalance of kallikrein-kinin system in chronic pancreatitis combined with obesity and results of its comprehensive correction

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    L.S. Babinets

    2017-11-01

    Full Text Available Background. Chronic pancreatitis is one of the most common diseases in general therapeutic practice. Significant role in the onset and progression of chronic pancreatitis is played by the activation of the kallikrein-kinin system (KKS, which is involved in the development of inflammation, blood coagulation and fibrinolysis, immune responses, the formation of pain, etc. Objective: to investigate the dynamics of indicators of the kallikrein-kinin system when using metadoxine in the comprehensive therapy of patients with chronic biliary pancreatitis associated with obesity. Materials and methods. 75 patients with chronic biliary pancreatitis combined with obesity were examined. They were divided into 2 groups. The first group (30 people received the standard treatment. The second group (45 people received the standard treatment and metadoxine. Results. Analyzing the results, it has been found a reliable positive dynamics of KKS indices in both groups after the treatment. However, patients in the second group showed a more significant positive dynamics of KKS parameters: the level of proteolytic activity has decreased by 9.0 %, the kallikrein — by 20.0 %, a1-proteinase inhibitor — by 7.2 %, and prekallikrein has increased by 6.4 %, a2-macroglobulin — by 10.8 %, kininase II — by 10.7 % as compared to group 1. Conclusions. The use of methadoxine in the comprehensive therapy of patients with chronic biliary pancreatitis associated with obesity contributed to a significant increase in the effectiveness of conventional treatment.

  2. Effect of an esterified glucomannan on laying hens exposed to combined mycotoxins (aflatoxin B1, zearalenone and fumonisin B1

    Directory of Open Access Journals (Sweden)

    A. Zaghini

    2011-03-01

    Full Text Available Mycotoxin toxicity depends on species, exposure time, age, sex, health and possible synergistic effects of other mycotoxins present in feed. In poultry, aflatoxin B1 (AFB1 and fumonisin B1 (FB1 are associated with poor growth performance, lowered feed utilization efficiency, liver damage and immunosuppression; metabolites may persist in tissues and eggs. Exposure of mature hens to zearalenone (ZEN apparently does not cause adverse effects, but ZEN residues and α and β zearalenol persist in liver and muscle (Kuiper-Goodman et al., 1987 and may be transmitted to egg yolk (Dailey et al., 1990. Various treatments and dietary strategies have been tried to reduce mycotoxin levels in contaminated commodities...

  3. Plexin-B1 silencing inhibits ovarian cancer cell migration and invasion

    International Nuclear Information System (INIS)

    Ye, Shuangmei; Chen, Yin; You, Lanying; Zhang, Yiqun; Xu, Gang; Zhou, Jianfeng; Ma, Ding; Wang, Shixuan; Hao, Xing; Zhou, Ting; Wu, Mingfu; Wei, Juncheng; Wang, Yongjun; Zhou, Li; Jiang, Xuefeng; Ji, Li

    2010-01-01

    Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro. Plexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKT Ser473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining. Expression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell proliferation was not

  4. Aflatoxin B1 use in radioimmunoassay

    International Nuclear Information System (INIS)

    Liu Yinkun; Zhang Xiaying; Chen Ruiqun; Gu Tianjue

    1987-01-01

    Antibodies against Aflatoxin B 1 (AFB 1 ) were obtained after multiple-site injections of bovine serum albumin-AFB 1 conjugate into rabbits. The greatest specific binding effciency of antibody for AFB 1 is 70∼80%. The sensitivity of radioimmunoassay (RIA) for AFB 1 is between 0.46∼2.3 ng. The retrievel rate of AFB 1 by RIA from intentionally contaminated serum and rice is between 70∼80%. Detailed methods for the preparation of conjugate, immune serum, and methods for antibody titer determination are described

  5. Effect of bauhinia bauhinioides kallikrein inhibitor on endothelial proliferation and intracellular calcium concentration.

    Science.gov (United States)

    Bilgin, M; Burgazli, K M; Rafiq, A; Mericliler, M; Neuhof, C; Oliva, M L; Parahuleva, M; Soydan, N; Doerr, O; Abdallah, Y; Erdogan, A

    2014-01-01

    Proteinase inhibitors act as a defensive system against predators e.g. insects, in plants. Bauhinia bauhinioides kallikrein inhibitor (BbKI) is a serine proteinase inhibitor, isolated from seeds of Bauhinia bauhinioides and is structurally similar to plant Kunitz-type inhibitors but lacks disulfide bridges. In this study we evaluated the antiproliferative effect of BbKI on endothelial cells and its impact on changes in membrane potential and intracellular calcium. HUVEC proliferation was significantly reduced by incubation with BbKI 50 and 100 µM 12% and 13%. Furthermore, BbKI (100 µM) exposure caused a significant increase in intracellular Ca2+ concentration by 35% as compared to untreated control. The intracellular rise in calcium was not affected by the absence of extracellular calcium. BBKI also caused a significant change in the cell membrane potential but the antiproliferative effect was independent of changes in membrane potential. BBKI has an antiproliferative effect on HUVEC, which is independent of the changes in membrane potential, and it causes an increase in intracellular Ca2+.

  6. OCT4B1 Regulates the Cellular Stress Response of Human Dental Pulp Cells with Inflammation

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    Lu Liu

    2017-01-01

    Full Text Available Introduction. Infection and apoptosis are combined triggers for inflammation in dental tissues. Octamer-binding transcription factor 4-B1 (OCT4B1, a novel spliced variant of OCT4 family, could respond to the cellular stress and possess antiapoptotic property. However, its specific role in dental pulpitis remains unknown. Methods. To investigate the effect of OCT4B1 on inflammation of dental pulp cells (DPCs, its expression in inflamed dental pulp tissues and DPCs was examined by in situ hybridization, real-time PCR, and FISH assay. OCT4B1 overexpressed DPCs model was established, confirmed by western blot and immunofluorescence staining, and then stimulated with Lipopolysaccharide (LPS. Apoptotic rate was determined by Hoechst/PI staining and FACS. Cell survival rate was calculated by CCK8 assay. Results. In situ hybridization, real-time PCR, and FISH assay revealed that OCT4B1 was extensively expressed in inflamed dental pulp tissues and DPCs with LPS stimulation. Western blot and immunofluorescence staining showed the expression of OCT4B1 and OCT4B increased after OCT4B1 transfection. Hoechst/PI staining and FACS demonstrated that less red/blue fluorescence was detected and apoptotic percentage decreased (3.45% after transfection. CCK8 demonstrated that the survival rate of pCDH-OCT4B1-flag cells increased. Conclusions. OCT4B1 plays an essential role in inflammation and apoptosis of DPCs. OCT4B might operate synergistically with OCT4B1 to reduce apoptosis.

  7. 118-B-1 excavation treatability test plan

    International Nuclear Information System (INIS)

    1994-07-01

    The Hanford 118-B-1 Burial Ground Treatability Study has been required by milestone change request number-sign M-15-93-04, dated September 30, 1993. The change request requires that a treatability test be conducted at the 100-B Area to obtain additional engineering information for remedial design of burial grounds receiving waste from 100 Area removal actions. This treatability study has two purposes: (1) to support development of the Proposed Plan (PP) and Record of Decision (ROD), which will identify the approach to be used for burial ground remediation, and (2) to provide specific engineering information for receiving waste generated from the 100 Area removal actions. Data generated from this test also will provide critical performance and cost information necessary for remedy evaluation in the detailed analysis of alternatives during preparation of the focused feasibility study (FFS). This treatability testing supports the following 100 Area alternatives: (1) excavation and disposal, and (2) excavation, sorting, (treatment), and disposal

  8. 118-B-1 excavation treatability test procedures

    International Nuclear Information System (INIS)

    Frain, J.M.

    1994-01-01

    This treatability study has two purposes: to support development of the approach to be used for burial ground remediation, and to provide specific engineering information for the design of burial grounds receiving waste generated from the 100 Area removal actions. Data generated from this test will also provide performance and cost information necessary for detailed analysis of alternatives for burial ground remediation. Further details on the test requirements, milestones and data quality objectives are described in detail in the 118-B-1 Excavation Treatability Test Plan (DOE/RL-94-43). These working procedures are intended for use by field personnel to implement the requirements of the milestone. A copy of the detailed Test Plan will be kept on file at the on-site field support trailer, and will be available for review by field personnel

  9. Skin barrier homeostasis in atopic dermatitis: feedback regulation of kallikrein activity.

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    Reiko J Tanaka

    Full Text Available Atopic dermatitis (AD is a widely spread cutaneous chronic disease characterised by sensitive reactions (eg. eczema to normally innocuous elements. Although relatively little is understood about its underlying mechanisms due to its complexity, skin barrier dysfunction has been recognised as a key factor in the development of AD. Skin barrier homeostasis requires tight control of the activity of proteases, called kallikreins (KLKs, whose activity is regulated by a complex network of protein interactions that remains poorly understood despite its pathological importance. Characteristic symptoms of AD include the outbreak of inflammation triggered by external (eg. mechanical and chemical stimulus and the persistence and aggravation of inflammation even if the initial stimulus disappears. These characteristic symptoms, together with some experimental data, suggest the presence of positive feedback regulation for KLK activity by inflammatory signals. We developed simple mathematical models for the KLK activation system to study the effects of feedback loops and carried out bifurcation analysis to investigate the model behaviours corresponding to inflammation caused by external stimulus. The model analysis confirmed that the hypothesised core model mechanisms capture the essence of inflammation outbreak by a defective skin barrier. Our models predicted the outbreaks of inflammation at weaker stimulus and its longer persistence in AD patients compared to healthy control. We also proposed a novel quantitative indicator for inflammation level by applying principal component analysis to microarray data. The model analysis reproduced qualitative AD characteristics revealed by this indicator. Our results strongly implicate the presence and importance of feedback mechanisms in KLK activity regulation. We further proposed future experiments that may provide informative data to enhance the system-level understanding on the regulatory mechanisms of skin barrier

  10. Effects of prolonged oral administration of fumonisin B1 and aflatoxin B1 in rats.

    Science.gov (United States)

    Pozzi, C R; Corrêa, B; Xavier, J G; Direito, G M; Orsi, R B; Matarazzo, S V

    2001-01-01

    The effects of prolonged oral administration (21 days) of fumonisin B1 (FB1) and aflatoxin B1 (AFB1) were evaluated on male Wistar rats. The animals were housed in individual metabolic cages and submitted to the following treatments: 1-0 microg AFB1 + 0 mg FB1/100g bw.; 2-72 microg AFB1+ 0 mg FB1/100 g bw; 3-0 microg AFB1 + 0.5 mg FB1 g bw; 4-0 microg AFB1 + 1.5 mg FB1/100 g bw; 5-72 microg AFB1 + 0.5 mg FB1/100g bw; 6-72 microgAFB1 + 1.5 mg FB1/100g bw. On day 21, the rats were sacrificed for evaluation. The results showed that treated animals presented differences in body weight and absolute/relative weights of liver and kidney as well as altered hepatic function and cholesterol blood levels. Rats fed with the greatest doses of AFB1 and FB1 gained less weight (2.79 g/day) at the end of the experimental period; their blood concentrations of liver enzymes aspartate aminotransferase (AST) and alkaline phosphatase (AP) were above control levels (130.35 micro/l and 471.00 micro/l, respectively). Blood cholesterol increased in the groups treated with the highest dose of FB1 or FB1 associated with AFB1. Histopathology revealed the occurrence of apoptosis in the liver of rats exposed to FB1. The association of aflatoxin B1 with fumonisin B1 at higher dose probably potentiated the effects of the higher dose of fumonisin B1 acting singly.

  11. Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb and correlate with integrin αvβ3 expression.

    Directory of Open Access Journals (Sweden)

    Shen Shen Fu

    Full Text Available BACKGROUND: Human tissue kallikrein (hTK plays an essential role in the physiological and pathological mechanisms of blood vessels. This study aimed to determine whether angiogenesis induced by endothelial progenitor cells (EPCs transduced with the adenovirus-mediated hTK gene could improve blood flow in rat hindlimb ischemia in vivo and to establish a promising mechanism in vitro. METHODS: EPCs transduced with adenovirus encoding hTK-162 (i.e., Ad/hTK-transduced EPCs or Ad/GFP-transduced EPCs were administered to Wister rats with hindlimb ischemia through therapeutic neovascularization. Muscular capillary density (MCD, blood flow (BF, and the number of myofibers were measured at days 7, 14, and 21 after treatment. Expressions of integrin αvβ3 and endothelial nitric oxide synthase (eNOS were detected on the surface of EPCs. RESULTS: MCD, BF, and the number of myofibers in rats with Ad/hTK-transduced EPCs remarkably increased at day 21 after treatment compared with rats with Ad/GFP-transduced EPCs or the control group (P<0.01. Expressions of integrin αvβ3 and eNOS protein on the surface of EPCs also increased in rats with Ad/hTK-transduced EPCs. The levels of integrin αvβ3 expression were reduced by PI3K and eNOS blockade, and the inhibitor of integrin αvβ3 abrogated the migration and adhesion of hTK-transduced EPCs (P<0.05. CONCLUSION: hTK gene delivery in vivo improves the natural angiogenic response to ischemia. The ability of hTK gene-transduced EPCs can be enhanced in vitro, in which integrin αvβ3 plays a role in the process.

  12. Involvement of skeletal renin-angiotensin system and kallikrein-kinin system in bone deteriorations of type 1 diabetic mice with estrogen deficiency.

    Science.gov (United States)

    Zhang, Yan; Wang, Liang; Liu, Jin-Xin; Wang, Xin-Luan; Shi, Qi; Wang, Yong-Jun

    This study was aimed to investigate the involvement of skeletal renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) in bone deteriorations of mice in response to the combination treatment of estrogen deficiency and hyperglycemia. The female C57BL/6J mice were sham-operated or ovariectomized with vehicle or streptozotocin (STZ) treatment. Two weeks later, the biochemistries in serum and urine were determined by standard colorimetric methods or ELISA. The H&E and TRAP staining were performed at the tibial proximal metaphysis. The polymerase chain reaction and immunoblotting were applied for molecular analysis on mRNA and protein expression. The mice after treating with ovariectomy and STZ showed the decreased level of serum Ca and the increased level of serum PTH and urine Ca. The H&E staining showed trabecular bone abnormalities as demonstrated by the loss, disconnection and separation of trabecular bone network as well as the loss of chondrocytes and appearance of chondrocyte cluster at growth plate of tibia. The significant increase of matured osteoclast number was shown in group with double treatments. The combination treatment significantly up-regulated mRNA expression of AGT, ACE, renin receptor, MMP-9 and CAII, and protein expression of renin, and decreased the ratio of OPG/RANKL and the expression of bradykinin receptors in bone tissue. Ovariectomy combined with STZ induction produced more detrimental actions on bone through the activation of local bone RAS and the down-regulation of bradykinin receptors, as compared to the respective single treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Autoradiographic research on cell proliferation of prenatal rat lung cells and their influence using the mitogen Kallikrein

    International Nuclear Information System (INIS)

    Bock-Lamberlin, P.R.

    1980-01-01

    In this work autoradiographic experiments were carried out on the kinetics of proliferation of four cell populations of the prenatal rat lung with the help of the determination of the 3 H-thymidine marker indices, with the following results: 1. The four studied cell populations exhibited variable proliferation rates on the twentieth or twenty-first day of development. 2. The strongest affect of the exogenously applied mitogen Kallikrein was demonstrated on the vessel wall cells, the next strongest on the bronchial epithelial cells, then the cartilage cells and finally the alveolar wall cells. 3. The mitogenic effect is dependent on dose. Higher doses significantly increased the 3 H-thymidine marker indices of the four cell populations tested in this work. 4. When the exposure time of the Kallikrein was extended by one hour this lead partially to stronger mitogenic effects than by the shorter exposure times at the same and higher dose levels of mitogen. 5. The 3 H-thymidine marker indices are dependent on the exposure time. 6. With increasing litter size, the 3 H indices as a rule decrease. (orig./MG) [de

  14. CD25+ B-1a Cells Express Aicda

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    Hiroaki Kaku

    2017-06-01

    Full Text Available B-1a cells are innate-like B-lymphocytes producing natural antibodies. Activation-induced cytidine deaminase (AID, a product of the Aicda gene, plays a central role in class-switch recombination and somatic hypermutation in B cells. Although a role for Aicda in B-1a cells has been suggested on the basis of experiments with knock out (KO mice, whether B-1a cells express Aicda, and if so, which B-1a cell subpopulation expresses Aicda, remains unknown. Here, we demonstrate that B-1 cells express Aicda, but at a level below that expressed by germinal center (GC B cells. We previously reported that B-1a cells can be subdivided based on CD25 expression. We show here that B-1a cell Aicda expression is concentrated in the CD25+ B-1a cell subpopulation. These results suggest the possibility that previous studies of memory B cells identified on the basis of Aicda expression may have inadvertently included an unknown number of CD25+ B-1a cells. Although B-1a cells develop normally in the absence of Aicda, a competitive reconstitution assay reveals enhanced vigor for AID KO B-1a cell bone marrow (BM progenitors, as compared with wild-type BM B-1 cell progenitors. These results suggest that AID inhibits the development of B-1a cells from BM B-1 cell progenitors in a competitive environment.

  15. Digestion of atopic allergens with trypsin α-chymotrypsin and pancreatic kallikrein, and influence of the allergens upon the proteolytic and esterolytic activity of these enzymes

    NARCIS (Netherlands)

    Berrens, L.

    1968-01-01

    The action of bovine trypsin, α-chymotrypsin and pancreatic kallikrein upon a number of atopic allergens has been studied by pH-stat measurements during short-term incubation. Most atopic allergens proved chemically resistant towards these enzymes. Graphs of enzyme susceptibility vs. the ratio of

  16. Role of CYP1B1 in PAH-DNA adduct formation and breast cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Goth-Goldstein, Regine; Russell, Marion L.; Muller, A.P.; Caleffi, M.; Eschiletti, J.; Graudenz, M.; Sohn, Michael D.

    2010-04-01

    This study investigated the hypothesis that increased exposure to polycyclic aromatic hydrocarbons (PAHs) increases breast cancer risk. PAHs are products of incomplete burning of organic matter and are present in cigarette smoke, ambient air, drinking water, and diet. PAHs require metabolic transformation to bind to DNA, causing DNA adducts, which can lead to mutations and are thought to be an important pre-cancer marker. In breast tissue, PAHs appear to be metabolized to their cancer-causing form primarily by the cytochrome P450 enzyme CYP1B1. Because the genotoxic impact of PAH depends on their metabolism, we hypothesized that high CYP1B1 enzyme levels result in increased formation of PAH-DNA adducts in breast tissue, leading to increased development of breast cancer. We have investigated molecular mechanisms of the relationship between PAH exposure, CYP1B1 expression and breast cancer risk in a clinic-based case-control study. We collected histologically normal breast tissue from 56 women (43 cases and 13 controls) undergoing breast surgery and analyzed these specimens for CYP1B1 genotype, PAH-DNA adducts and CYP1B1 gene expression. We did not detect any difference in aromatic DNA adduct levels of cases and controls, only between smokers and non-smokers. CYP1B1 transcript levels were slightly lower in controls than cases, but the difference was not statistically significant. We found no correlation between the levels of CYP1B1 expression and DNA adducts. If CYP1B1 has any role in breast cancer etiology it might be through its metabolism of estrogen rather than its metabolism of PAHs. However, due to the lack of statistical power these results should be interpreted with caution.

  17. Aflatoxin B1: Mechanism of mutagenesis

    Directory of Open Access Journals (Sweden)

    Regina M. Santella

    2007-02-01

    Full Text Available

    Aflatoxins are a group of toxic and carcinogenic fungal metabolites that frequently contaminate corn, peanuts and other products. Aflatoxin B1 (AFB1, the most potent of these, is metabolized by the cytochrome P450 system into a number of hydroxylated metabolites and glutathione conjugates in the process of conversion to more hydrophilic forms for urinary excretion. Unfortunately, one of these metabolites is the aflatoxin-8,9-epoxide that is produced in two forms, endo and exo. Glutathione S-transferases (GST are able to conjugate and detoxify this reactive intermediate. Species differences in susceptibility to the effects of AFB1 are partially related to differences in expression of specific GSTs that are able to conjugate the epoxide to glutathione. The exo epoxide is able to intercalate into DNA and this is followed by reaction of the C8 position of the epoxide with the N7 position of guanine.

    NMR studies of oligonucleotide duplexes containing the adduct have demonstrated that the adduct exists with the aromatic portion intercalated on the 5' face of the guanine residue with Watson-Crick base pairing maintained.

    However, this covalent adduct is chemically unstable due to the charge on the ribose ring. As a result, the guanine can be released from the DNA leaving an apurinic site. This released guanine adduct can be detected in the urine and serves as a biomarker of exposure to AFB1. Alternatively, the ribose ring opens forming a stable formamidopyrimidine (FAPY adduct. This adduct somewhat stabilizes the DNA duplex. Time course studies in animals have demonstrated that the N7 adduct is rapidly removed, probably because it causes more distortion in the helix, while the FAPY adduct is more

  18. 77 FR 42707 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-07-20

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-35] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... Force (DAY) [[Page 42709

  19. Hydroxysteroid sulfotransferase SULT2B1b promotes hepatocellular carcinoma cells proliferation in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Xiaoming Yang

    Full Text Available Hydroxysteroid sulfotransferase 2B1b (SULT2B1b is highly selective for the addition of sulfate groups to 3β-hydroxysteroids. Although previous reports have suggested that SULT2B1b is correlated with cell proliferation of hepatocytes, the relationship between SULT2B1b and the malignant phenotype of hepatocarcinoma cells was not clear. In the present study, we found that SULT2B1 was comparatively higher in the human hepatocarcinoma tumorous tissues than their adjacent tissues. Besides, SULT2B1b overexpression promoted the growth of the mouse hepatocarcinoma cell line Hepa1-6, while Lentivirus-mediated SULT2B1b interference inhibited growth as assessed by the CCK-8 assay. Likewise, inhibition of SULT2B1b expression induced cell-cycle arrest and apoptosis in Hepa1-6 cells by upregulating the expression of FAS, downregulating the expression of cyclinB1, BCL2 and MYC in vitro and in vivo at both the transcript and protein levels. Knock-down of SULT2B1b expression significantly suppressed tumor growth in nude mouse xenografts. Moreover, proliferation rates and SULT2B1b expression were highly correlated in the human hepatocarcinoma cell lines Huh-7, Hep3B, SMMC-7721 and BEL-7402 cells. Knock-down of SULT2B1b inhibited cell growth and cyclinB1 levels in human hepatocarcinoma cells and suppressed xenograft growth in vivo. In conclusion, SULT2B1b expression promotes proliferation of hepatocellular carcinoma cells in vitro and in vivo, which may contribute to the progression of HCC.

  20. SoxB1-driven transcriptional network underlies neural-specific interpretation of morphogen signals.

    Science.gov (United States)

    Oosterveen, Tony; Kurdija, Sanja; Ensterö, Mats; Uhde, Christopher W; Bergsland, Maria; Sandberg, Magnus; Sandberg, Rickard; Muhr, Jonas; Ericson, Johan

    2013-04-30

    The reiterative deployment of a small cadre of morphogen signals underlies patterning and growth of most tissues during embyogenesis, but how such inductive events result in tissue-specific responses remains poorly understood. By characterizing cis-regulatory modules (CRMs) associated with genes regulated by Sonic hedgehog (Shh), retinoids, or bone morphogenetic proteins in the CNS, we provide evidence that the neural-specific interpretation of morphogen signaling reflects a direct integration of these pathways with SoxB1 proteins at the CRM level. Moreover, expression of SoxB1 proteins in the limb bud confers on mesodermal cells the potential to activate neural-specific target genes upon Shh, retinoid, or bone morphogenetic protein signaling, and the collocation of binding sites for SoxB1 and morphogen-mediatory transcription factors in CRMs faithfully predicts neural-specific gene activity. Thus, an unexpectedly simple transcriptional paradigm appears to conceptually explain the neural-specific interpretation of pleiotropic signaling during vertebrate development. Importantly, genes induced in a SoxB1-dependent manner appear to constitute repressive gene regulatory networks that are directly interlinked at the CRM level to constrain the regional expression of patterning genes. Accordingly, not only does the topology of SoxB1-driven gene regulatory networks provide a tissue-specific mode of gene activation, but it also determines the spatial expression pattern of target genes within the developing neural tube.

  1. 26 CFR 31.3306(b)-1 - Wages.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Wages. 31.3306(b)-1 Section 31.3306(b)-1... Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(b)-1 Wages. (a) Applicable law and... after 1938 constitutes wages is determined under section 3306(b). Accordingly, only remuneration paid...

  2. 26 CFR 301.7701(b)-1 - Resident alien.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Resident alien. 301.7701(b)-1 Section 301.7701... ADMINISTRATION PROCEDURE AND ADMINISTRATION Definitions § 301.7701(b)-1 Resident alien. (a) Scope. Section 301.7701(b)-1(b) provides rules for determining whether an alien individual is a lawful permanent resident...

  3. 26 CFR 1.267(b)-1 - Relationships.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Relationships. 1.267(b)-1 Section 1.267(b)-1...) INCOME TAXES Items Not Deductible § 1.267(b)-1 Relationships. (a) In general. (1) The persons referred to... partnership separately. Therefore, if the other person and a partner are within any one of the relationships...

  4. Assessment of human exposure to fumonisin B1

    NARCIS (Netherlands)

    Nijs, M. de; Egmond, H.P. van; Nauta, M.; Rombouts, F.M.; Notermans, S.H.W.

    1998-01-01

    Fumonisin B1 is currently regarded as the most significant mycotoxin produced by Fusarium spp. It has carcinogenic properties and may play a role in the etiology of human esophageal cancer. The human population is exposed to fumonisin B1 primarily by intake of fumonisin B1-contaminated maize. Maize

  5. Risk assessment of fumonisin B1 in the Netherlands

    NARCIS (Netherlands)

    Bakker MI; Speijers GJA; Paulsch WE; van Egmond HP; SIR; ARO

    2004-01-01

    Fumonisine B1 is een mycotoxine, dat kan worden gevormd door bepaalde Fusarium schimmels. Het toxine wordt vooral in mais (-producten) aangetroffen, maar het kan ook voorkomen in tarwe (-producten). De inname van fumonisine B1 in de Nederlandse populatie is geschat door fumonisine B1 concentraties

  6. Use of radiolabeled monoclonal anti-B1 antibody for B lymphocyte imaging in Rhesus monkeys

    International Nuclear Information System (INIS)

    Letvin, N.L.; Zalutsky, M.R.; Chalifoux, L.V.; Atkins, H.L.

    1987-01-01

    Imaging tissues rich in B lymphocytes in man using a radiolabeled monoclonal anti-B cell antibody would be extremely useful in the clinical staging of non-Hodgkins lymphomas. Studies were done in rhesus monkeys using radiolabeled monoclonal anti-B1 antibody to determine the feasibility of such an approach. Immunohistologic studies demonstrated that infused monoclonal anti-B1 binds in vivo with specificity to B cells in lymph nodes and spleen. The kinetics of clearance of 131 I-labeled anti-B1 were determined. The B lymphocyte-rich spleen could be readily visualized by gamma camera scanning without significant background and without the need for image intensification or blood background subtraction techniques. These data support the feasibility of using anti-B1 for staging B cell lymphomas in man. (author)

  7. Effects of oral administration of aflatoxin B1 and fumonisin B1 in rabbits (Oryctolagus cuniculus).

    Science.gov (United States)

    Orsi, R B; Oliveira, C A F; Dilkin, P; Xavier, J G; Direito, G M; Corrêa, B

    2007-12-15

    The effects of prolonged oral administration (21 days) of fumonisin B(1) (FB(1)) and aflatoxin B(1) (AFB(1)) were studied in male New Zealand rabbits by clinical, pathological, biochemical and sphingolipid analyses. Twenty-four animals were randomly divided into the following four experimental groups: (A) 0 mg FB(1)+0 microg AFB(1)/(kg body weight(bw)day) (control); (B) 0 mg FB(1)+30 microg AFB(1)/(kg bw day); (C) 1.5 mg FB(1)/(kg bw day)+30 microg AFB(1)/(kg bw day); (D) 1.5 mg FB(1)/(kg bw day)+0 microg AFB(1). Animals from group B and principally from group C presented clinical signs of intoxication. Rabbits from group C presented a lower body weight gain than controls. Differences were observed between intoxicated rabbits and controls with respect to absolute and relative liver and kidney weight, hepatic function, serum urea and creatinine levels and Sa/So ratio. The most frequent hepatic and renal injuries were vacuolar degeneration of the liver and kidney as shown by the histopathological and serum biochemical results. Combined administration of AFB(1) and FB(1) resulted in synergistic toxic effects both in the liver and in the kidney, but hepatic injuries were more marked.

  8. Up-regulation and subcellular localization of hnRNP A2/B1 in the development of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Cui, Huaqing; Wu, Feng; Sun, Yanling; Fan, Guocai; Wang, Qingming

    2010-01-01

    Hepatocellular carcinoma (HCC) is one of the world's leading causes of death among cancer patients. It is important to find a new biomarker that diagnoses HCC and monitors its treatment. In our previous work, we screened a single-chain antibody (scFv) N14, which could specifically recognize human HepG2 HCC cells but not human non-cancerous liver LO2 cells. However, the antigen it recognized in the cells remained unknown. Recombinant scFv N14 antibody was expressed as an active antibody. Using this antibody with a combination of immunological and proteomic approaches, we identified the antigen of scFv N14 antibody as the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1). The expression of hnRNP A2/B1 in HCC cells was then investigated by semi-quantitative RT-PCR and immunohistochemistry. We found that the up-regulation of hnRNP A2/B1 was measured at both transcriptional and translational levels in rat HCC cells but not in rat hepatic cells. We also found that in various human hepatic tissues, hnRNP A2/B1 was highly expressed in both human hepatitis virus positive liver tissues and human HCC tissues but not in normal liver tissues. Interestingly, we observed that the localization of hnRNP A2/B1 in HCC cells was altered during the development of HCC. In human hepatitis virus infected tissues hnRNP A2/B1 resides exclusively in the nuclei of hepatocytes. However, when the HCC progressed from a well differentiated to a poorly differentiated stage, hnRNP A2/B1 was increasingly localized in the cytoplasm. In contrast, the HCC tissues with hnRNP A2/B1 highly expressed in the nucleus decreased. This work is the first to show that hnRNP A2/B1 is the antigen specifically recognized by the scFv N14 antibody in HCC cells. The over-expression of hnRNP A2/B1 was confirmed in cultured human and rat HCC cell lines, human virus related hepatitis liver tissues and human HCC tissues. The increased localization of hnRNP A2/B1 in the cytoplasm of HCC cells was revealed

  9. Kinin B1 receptors contributes to acute pain following minor surgery in humans

    Directory of Open Access Journals (Sweden)

    Brahim Jaime S

    2010-02-01

    Full Text Available Abstract Background Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in response to inflammation. However, little is known about the regulatory effects of kinin receptors on the onset of acute inflammation and inflammatory pain in humans. The present study investigated the changes in gene expression of kinin receptors and the levels of their endogenous ligands at an early time point following tissue injury and their relation to clinical pain, as well as the effect of COX-inhibition on their expression levels. Results Tissue injury resulted in a significant up-regulation in the gene expression of B1 and B2 receptors at 3 hours post-surgery, the onset of acute inflammatory pain. Interestingly, the up-regulation in the gene expression of B1 and B2 receptors was positively correlated to pain intensity only after ketorolac treatment, signifying an interaction between prostaglandins and kinins in the inflammatory pain process. Further, the gene expression of both B1 and B2 receptors were correlated. Following tissue injury, B1 ligands des-Arg9-BK and des-Arg10-KD were significantly lower at the third hour compared to the first 2 hours in both the placebo and the ketorolac treatment groups but did not differ significantly between groups. Tissue injury also resulted in the down-regulation of TRPV1 gene expression at 3 hours post-surgery with no significant effect by ketorolac treatment. Interestingly, the change in gene expression of TRPV1 was correlated to the change in gene expression of B1 receptor but not B2 receptor. Conclusions These results provide evidence at the transcriptional level in a clinical model of tissue injury that up-regulation of kinin receptors are involved in the development of the

  10. Endothelial cell permeability during hantavirus infection involves factor XII-dependent increased activation of the kallikrein-kinin system.

    Directory of Open Access Journals (Sweden)

    Shannon L Taylor

    Full Text Available Hemorrhagic fever with renal syndrome (HFRS and hantavirus pulmonary syndrome (HPS are diseases caused by hantavirus infections and are characterized by vascular leakage due to alterations of the endothelial barrier. Hantavirus-infected endothelial cells (EC display no overt cytopathology; consequently, pathogenesis models have focused either on the influx of immune cells and release of cytokines or on increased degradation of the adherens junction protein, vascular endothelial (VE-cadherin, due to hantavirus-mediated hypersensitization of EC to vascular endothelial growth factor (VEGF. To examine endothelial leakage in a relevant in vitro system, we co-cultured endothelial and vascular smooth muscle cells (vSMC to generate capillary blood vessel-like structures. In contrast to results obtained in monolayers of cultured EC, we found that despite viral replication in both cell types as well as the presence of VEGF, infected in vitro vessels neither lost integrity nor displayed evidence of VE-cadherin degradation. Here, we present evidence for a novel mechanism of hantavirus-induced vascular leakage involving activation of the plasma kallikrein-kinin system (KKS. We show that incubation of factor XII (FXII, prekallikrein (PK, and high molecular weight kininogen (HK plasma proteins with hantavirus-infected EC results in increased cleavage of HK, higher enzymatic activities of FXIIa/kallikrein (KAL and increased liberation of bradykinin (BK. Measuring cell permeability in real-time using electric cell-substrate impedance sensing (ECIS, we identified dramatic increases in endothelial cell permeability after KKS activation and liberation of BK. Furthermore, the alterations in permeability could be prevented using inhibitors that directly block BK binding, the activity of FXIIa, or the activity of KAL. Lastly, FXII binding and autoactivation is increased on the surface of hantavirus-infected EC. These data are the first to demonstrate KKS activation

  11. B1 -sensitivity analysis of quantitative magnetization transfer imaging.

    Science.gov (United States)

    Boudreau, Mathieu; Stikov, Nikola; Pike, G Bruce

    2018-01-01

    To evaluate the sensitivity of quantitative magnetization transfer (qMT) fitted parameters to B 1 inaccuracies, focusing on the difference between two categories of T 1 mapping techniques: B 1 -independent and B 1 -dependent. The B 1 -sensitivity of qMT was investigated and compared using two T 1 measurement methods: inversion recovery (IR) (B 1 -independent) and variable flip angle (VFA), B 1 -dependent). The study was separated into four stages: 1) numerical simulations, 2) sensitivity analysis of the Z-spectra, 3) healthy subjects at 3T, and 4) comparison using three different B 1 imaging techniques. For typical B 1 variations in the brain at 3T (±30%), the simulations resulted in errors of the pool-size ratio (F) ranging from -3% to 7% for VFA, and -40% to > 100% for IR, agreeing with the Z-spectra sensitivity analysis. In healthy subjects, pooled whole-brain Pearson correlation coefficients for F (comparing measured double angle and nominal flip angle B 1 maps) were ρ = 0.97/0.81 for VFA/IR. This work describes the B 1 -sensitivity characteristics of qMT, demonstrating that it varies substantially on the B 1 -dependency of the T 1 mapping method. Particularly, the pool-size ratio is more robust against B 1 inaccuracies if VFA T 1 mapping is used, so much so that B 1 mapping could be omitted without substantially biasing F. Magn Reson Med 79:276-285, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  12. Identification of New Aflatoxin B1-Degrading Bacteria from Iran

    Directory of Open Access Journals (Sweden)

    Fahimeh Sangi

    2018-04-01

    Full Text Available Background: Aflatoxin B1 (AFB1 is a mutagenic and carcinogenic compound mainly produced by the Aspergillus parasiticus, A. flavus, A. nomius, A. tamari, and A. pseudotamarii. AFB1 biodegradation is the most important strategy for reducing AFB1 in plant tissues. Bacteria can deactivate and biodegrade AFB1 for effective detoxification of contaminated products. The present study investigated the efficiency of AFB1 degradation by soil bacteria from the Southern Khorasan Province in Eastern Iran by thin-layer and high-performance liquid chromatography during 2014–2015. Methods: DNA was extracted from AFB1-degrading isolates by the cetyltrimethylammonium bromide method and the 16S rRNA gene was amplified with the 27f and 1492r general bacterial primers and the sequences were used to identify the isolates based on their similarity to Gene Bank sequences of known bacterial species. Results: We isolated five strains from four species of AFB1-degrading bacteria from Birjand plain, including Bacillus pumilus, two isolates of Ochrobactrum pseudogrigonens, Pseudomonas aeruginosa, and Enterobacter cloace, which had AFB1-degrading activities of 88%, 78%, 61%, 58%, and 51%, respectively. Conclusion: We provide the first demonstration of AFB1 degradation by B. pumilus in from Iran and the first report identifying O. pseudogrigonens and E. cloace species as having AFB1-degrading activity.

  13. Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer

    DEFF Research Database (Denmark)

    Ulmert, David; Vickers, Andrew J; Scher, Howard I

    2012-01-01

    The utility of conventional prostate-specific antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase...... of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon(®)), a novel GnRH antagonist....

  14. 26 CFR 1.280B-1 - Demolition of structures.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise allowable...

  15. Determination of aflatoxin B1 in food products in Thailand ...

    African Journals Online (AJOL)

    Aflatoxin B1 is generally found in feed and food stuff, such as cereal and all products derived from cereals, including processed cereals since it has been proven to be at least partly resistant to food processing methods. Hence, the aim of this study was to determine the possibility of contamination of aflatoxin B1 in food ...

  16. SerpinB1 Promotes Pancreatic β Cell Proliferation

    Energy Technology Data Exchange (ETDEWEB)

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas; Hu, Jiang; Zhou, Jian-Ying; Shirakawa, Jun; Hou, Lifei; Goodman, Jessica; Karampelias, Christos; Qiang, Guifeng; Boucher, Jeremie; Martinez, Rachael; Gritsenko, Marina A.; De Jesus, Dario F.; Kahraman, Sevim; Bhatt, Shweta; Smith, Richard D.; Beer, Hans-Dietmar; Jungtrakoon, Prapaporn; Gong, Yanping; Goldfine, Allison B.; Liew, Chong Wee; Doria, Alessandro; Andersson, Olov; Qian, Wei-Jun; Remold-O’Donnell, Eileen; Kulkarni, Rohit N.

    2016-01-01

    Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuated β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.

  17. 26 CFR 301.6226(b)-1 - 5-percent group.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false 5-percent group. 301.6226(b)-1 Section 301.6226... ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6226(b)-1 5-percent group. (a) In general. All members of a 5-percent group shall join in filing any petition for judicial review. The...

  18. 26 CFR 301.6223(b)-1 - Notice group.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Notice group. 301.6223(b)-1 Section 301.6223(b... ADMINISTRATION PROCEDURE AND ADMINISTRATION Assessment In General § 301.6223(b)-1 Notice group. (a) In general. If a group of partners having in the aggregate a 5 percent or more interest in the profits of a...

  19. Risk assessment of fumonisin B1 in the Netherlands

    NARCIS (Netherlands)

    Bakker MI; Speijers GJA; Paulsch WE; Egmond HP van; SIR; ARO

    2004-01-01

    Fumonisin B1 is a mycotoxin that can be produced by certain Fusarium species. The toxin is found, in particular, in maize and maize products, but occurrence in boeth wheat and wheat products, and rice and rice products, has also been reported. The intake of fumonisin B1 by the population in the

  20. OECD 28-days oral toxicity study on fumonisin B1

    NARCIS (Netherlands)

    Nijs M de; Egmond HP van; Jong WH de; Loveren H van; LPI; ARO; MGB

    1999-01-01

    Het beschreven experiment werd uitgevoerd om inzicht te verkrijgen over effecten van lage doseringen fumonisine B1 op target organen en het immuunsysteem. Mannelijke ratten van drie weken oud werden oraal via maagsonde behandeld met 0, 0,19, 0,75 of 3 mg/kg lichaamsgewicht fumonisine B1,

  1. 78 FR 46579 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-08-01

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-30] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...: FMS case YAD-$22M-16Jan10. (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None...

  2. 76 FR 17111 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-03-28

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-10] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  3. 78 FR 62590 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-10-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-43] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None (vii) Sensitivity of...

  4. 76 FR 37071 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-06-24

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-03] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  5. 75 FR 60424 - 36(b)(1) Arms Sales Notifications

    Science.gov (United States)

    2010-09-30

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-28 and 10-30] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of two section 36(b)(1) arms sales notifications to...

  6. 78 FR 78939 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-12-27

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-68] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...-$98M (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: N/A (vii) Sensitivity of...

  7. 76 FR 37075 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-06-24

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-77] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  8. 76 FR 43659 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-07-21

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-28] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  9. 78 FR 78941 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-12-27

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-70] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... any: FMS Case GAC--$82M--12Mar10 (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid...

  10. 76 FR 27026 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-05-10

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-13] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  11. 76 FR 37078 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-06-24

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-68] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  12. 77 FR 42709 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-07-20

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-24] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... Cases, if any: None (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None (vii...

  13. 77 FR 60384 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-10-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-54] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is...

  14. 76 FR 43662 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-07-21

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-15] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...) Military Department: Navy (AAR) (v) Prior Related Cases, if any: None (vi) Sales Commission, Fee, etc...

  15. 75 FR 61440 - 36(b)(1) Arms Sales Notifications

    Science.gov (United States)

    2010-10-05

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-47, 10-48, and 10-51] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of three section 36(b)(1) arms sales notifications...

  16. 77 FR 37884 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-06-25

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-19] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... Department: Navy (LAN). (v) Prior Related Cases, if any: None. (vi) Sales Commission, Fee, etc., Paid...

  17. 76 FR 72686 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-11-25

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-47] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This..., if any: FMS Case FAL-$73M-6Apr11 (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed To Be...

  18. 75 FR 29998 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-05-28

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 10-22] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification to fulfill the...

  19. 76 FR 29212 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-05-20

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-75] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  20. 78 FR 26324 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-05-06

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-20] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... Gasoline). (v) Prior Related Cases, if any: Numerous cases dating back to 1995. (vi) Sales Commission, Fee...

  1. 75 FR 48646 - 36(b)(1) Arms Sales Notifications

    Science.gov (United States)

    2010-08-11

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-27, 10-31 and 10-41] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of three section 36(b)(1) arms sales notifications...

  2. 75 FR 23247 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-05-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 10-08] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification to fulfill the...

  3. 76 FR 60461 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-09-29

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-27] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... any: FMS Case JAH-$402 million-11Dec91. FMS Case ZUF-$375 million-22Dec08. (vi) Sales Commission, Fee...

  4. 78 FR 76114 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-12-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-66] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None (vii) Sensitivity of Technology...

  5. 77 FR 42711 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-07-20

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-20] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This..., Amd 3). (v) Prior Related Cases, if any: FMS case ULJ-$46M-15Jan10. (vi) Sales Commission, Fee, etc...

  6. 75 FR 27314 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-05-14

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 10-19] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification to fulfill the...

  7. 75 FR 11865 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-03-12

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 10-12] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification to fulfill the...

  8. 78 FR 76112 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-12-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-63] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... case LAJ-$22M--8Mar07 FMS case GAU-$45M--25Jul08 FMS case LAL-$293M--5Jan09 (vi) Sales Commission, Fee...

  9. 78 FR 42051 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-07-15

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-26] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... any: None (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None (vii...

  10. 75 FR 76418 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-12-08

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-65] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  11. 75 FR 76415 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-12-08

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-72] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  12. 78 FR 32632 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-05-31

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-28] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...-31Dec06. FMS case NZU-$93 million-19Aug10. (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to...

  13. 75 FR 74011 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-11-30

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-24] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  14. 78 FR 26326 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-05-06

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-09] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...-20Feb08. (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None. (vii) Sensitivity of...

  15. 78 FR 62600 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-10-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-47] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...: None (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed To Be Paid: None (vii) Sensitivity of...

  16. 75 FR 76412 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-12-08

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-69] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  17. 77 FR 60391 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-10-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-32] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is...

  18. 76 FR 60455 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-09-29

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-71] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... support. (iv) Military Department: Army (UJT). (v) Prior Related Cases, if any: None. (vi) Sales...

  19. 75 FR 74014 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-11-30

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-49] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  20. 76 FR 27022 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-05-10

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-12] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  1. 77 FR 60387 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-10-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-26] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is...

  2. 77 FR 51780 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-08-27

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-42] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... support. (iv) Military Department: Air Force (QAZ). (v) Prior Related Cases, if any: None. (vi) Sales...

  3. 78 FR 26328 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-05-06

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-06] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...) Prior Related Cases, if any: FMS case QAA-$301M-3Dec08. (vi) Sales Commission, Fee, etc., Paid, Offered...

  4. 77 FR 70151 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-11-23

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-56] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...: Army (UAK). (v) Prior Related Cases, if any: None. (vi) Sales Commission, Fee, etc., Paid, Offered, or...

  5. 77 FR 13564 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-03-07

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-53] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This..., if any: None (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None (vii...

  6. 78 FR 62588 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-10-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-53] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None (vii) Sensitivity of Technology...

  7. 77 FR 12037 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-02-28

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-11] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... support. (iv) Military Department: Navy (SAF). (v) Prior Related Cases, if any: None. (vi) Sales...

  8. 76 FR 60459 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-09-29

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-19] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...-$280 million-29Nov07. (vi) Sales Commission, Fee, etc., Paid, Offered, or Agreed to be Paid: None. (vii...

  9. 75 FR 76408 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2010-12-08

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-73] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  10. 77 FR 46417 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-08-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-39] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...: USA (UAF) (v) Prior Related Cases, if any: FMS case UAD-$95M-23Jan12 (vi) Sales Commission, Fee, etc...

  11. 76 FR 60467 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2011-09-29

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-34] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...: a Foreign Military Sales Order II (FMSO II) to provide funds for blanket order requisitions, under...

  12. 78 FR 69073 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-11-18

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-59] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...) Military Department: Air Force (QAH) (v) Prior Related Cases: None (vi) Sales Commission, Fee, etc., Paid...

  13. 78 FR 54242 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-09-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-38] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...--$54.3M--5May04 FMS case QZX--$62.4M--24Dec03 FMS case CCZ--$48.4M--12Aug02 [[Page 54244

  14. Studies on coagulation, fibrinolysis, kallikrein-kinin and complement activation in systemic and pulmonary circulation during hip arthroplasty with acrylic cement.

    Science.gov (United States)

    Dahl, O E; Molnar, I; Vinje, A; Rø, J S; Kierulf, P; Andersen, A B; Dalaker, K; Prydz, H

    1988-06-15

    This study was designed to evaluate the contribution of the plasma cascade systems to the cardiopulmonary complications, occasionally leading to sudden death during hip arthroplasty using acrylic cement. The intraoperative pattern following uneventful surgery was therefore investigated in 8 patients with osteoarthrosis with frequent sampling from the radial and pulmonary arteries. The following general findings emerged: A gradual consumption of coagulation factors (platelets, fibrinogen, factor VII, antithrombin III), fibrinolytic components (plasminogen, alpha-2-antiplasmin), kallikrein-kinin factors (prekallikrein, kallikrein inhibitor) and complement factors (C3c, C4) was observed. Some intrapulmonary proteolytic inhibition was noticed as evidenced by lower arterial than mixed venous blood levels of alpha-2-antiplasmin and kallikrein inhibitor. Insignificant changes occurred for factor VII-phospholipid complex. A rapid, massive and transient increase in fibrinopeptide A (FPA) values in the radial artery, as opposed to the moderate increase in the pulmonary artery, was found immediately after reaming and broaching of bone. This probably reflected intrapulmonary fibrinogen to fibrin conversion, reaching a maximum 15-20 minutes before the femoral implantation. As estimated from the FPA arterial peak values and the fall in fibrinogen concentrations, approximately 5-10% of the circulating fibrinogen molecules were devoided of FPA during this intraoperative phase. The marked a-v difference in FPA level supports earlier findings of intrapulmonary fibrin formation and deposition. This process, however preceded the critical period of cardiorespiratory collapse (CRC) by at least 15 minutes, and may thus predispose to this complication.

  15. Wind tunnel tests of Risø-B1-18 and Risø-B1-24

    DEFF Research Database (Denmark)

    Fuglsang, P.; Bak, Christian; Gaunaa, Mac

    2003-01-01

    This report contains 2D measurements of the Risø-B1-18 and Risø-B1-24 airfoils. The aerodynamic properties were derived from pressure measurements on the airfoil surface and in the wake. The measurements were conducted in the VELUX open jet wind tunnel,which has a background turbulence intensity...

  16. Activation of the kinin B1 receptor attenuates melanoma tumor growth and metastasis.

    Directory of Open Access Journals (Sweden)

    Patricia Dillenburg-Pilla

    Full Text Available Melanoma is a very aggressive tumor that does not respond well to standard therapeutic approaches, such as radio- and chemotherapies. Furthermore, acquiring the ability to metastasize in melanoma and many other tumor types is directly related to incurable disease. The B1 kinin receptor participates in a variety of cancer-related pathophysiological events, such as inflammation and angiogenesis. Therefore, we investigated whether this G protein-coupled receptor plays a role in tumor progression. We used a murine melanoma cell line that expresses the kinin B1 receptor and does not express the kinin B2 receptor to investigate the precise contribution of activation of the B1 receptor in tumor progression and correlated events using various in vitro and in vivo approaches. Activation of the kinin B1 receptor in the absence of B2 receptor inhibits cell migration in vitro and decreases tumor formation in vivo. Moreover, tumors formed from cells stimulated with B1-specific agonist showed several features of decreased aggressiveness, such as smaller size and infiltration of inflammatory cells within the tumor area, higher levels of pro-inflammatory cytokines implicated in the host anti-tumor immune response, lower number of cells undergoing mitosis, a poorer vascular network, no signs of invasion of surrounding tissues or metastasis and increased animal survival. Our findings reveal that activation of the kinin B1 receptor has a host protective role during murine melanoma tumor progression, suggesting that the B1 receptor could be a new anti-tumor GPCR and provide new opportunities for therapeutic targeting.

  17. Influence of Kernel Age on Fumonisin B1 Production in Maize by Fusarium moniliforme

    Science.gov (United States)

    Warfield, Colleen Y.; Gilchrist, David G.

    1999-01-01

    Production of fumonisins by Fusarium moniliforme on naturally infected maize ears is an important food safety concern due to the toxic nature of this class of mycotoxins. Assessing the potential risk of fumonisin production in developing maize ears prior to harvest requires an understanding of the regulation of toxin biosynthesis during kernel maturation. We investigated the developmental-stage-dependent relationship between maize kernels and fumonisin B1 production by using kernels collected at the blister (R2), milk (R3), dough (R4), and dent (R5) stages following inoculation in culture at their respective field moisture contents with F. moniliforme. Highly significant differences (P ≤ 0.001) in fumonisin B1 production were found among kernels at the different developmental stages. The highest levels of fumonisin B1 were produced on the dent stage kernels, and the lowest levels were produced on the blister stage kernels. The differences in fumonisin B1 production among kernels at the different developmental stages remained significant (P ≤ 0.001) when the moisture contents of the kernels were adjusted to the same level prior to inoculation. We concluded that toxin production is affected by substrate composition as well as by moisture content. Our study also demonstrated that fumonisin B1 biosynthesis on maize kernels is influenced by factors which vary with the developmental age of the tissue. The risk of fumonisin contamination may begin early in maize ear development and increases as the kernels reach physiological maturity. PMID:10388675

  18. Risk assessment of fumonisin B1 in the Netherlands

    OpenAIRE

    Bakker MI; Speijers GJA; Paulsch WE; van Egmond HP; SIR; ARO

    2004-01-01

    Fumonisin B1 is a mycotoxin that can be produced by certain Fusarium species. The toxin is found, in particular, in maize and maize products, but occurrence in boeth wheat and wheat products, and rice and rice products, has also been reported. The intake of fumonisin B1 by the population in the Netherlands was estimated in an exposure assessment using data on concentrations of fumonisin B1 in different food products combined with the consumption rate of these products. From the (limited) resu...

  19. Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

    Science.gov (United States)

    Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

    2018-06-01

    Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  20. Osmotic stress upregulates the transcription of thiamine (vitamin B1 ...

    African Journals Online (AJOL)

    Osmotic stress upregulates the transcription of thiamine (vitamin B1) ... Oil palm's responses in terms of the expression profiles of these two thiamine biosynthesis genes to an osmotic stress inducer, polyethylene glycol ... from 32 Countries:.

  1. ACTH Regulation of Adrenal SR-B1

    Directory of Open Access Journals (Sweden)

    Wen-Jun eShen

    2016-05-01

    Full Text Available The adrenal gland is one of the prominent sites for steroid hormone synthesis. Lipoprotein-derived cholesterol esters delivered via scavenger receptor, class B type 1 (SR-B1 constitute the dominant source of cholesterol for steroidogenesis, particularly in rodents. ACTH stimulates steroidogenesis through downstream actions on multiple components involved in steroidogenesis. Both acute and chronic ACTH treatment can modulate SR-B1 function including its transcription, its post transcriptional stability, its phosphorylation and dimerization status, as well as its interaction with other protein partners; all of which result in changes in the ability of SR-B1 to mediate HDL-cholesterol ester uptake and the supply of cholesterol for conversion to steroids. Here we provide a review of the recent findings on the regulation of adrenal SR-B1 function by ACTH.

  2. BRAF activated non-coding RNA (BANCR) promoting gastric cancer cells proliferation via regulation of NF-κB1

    International Nuclear Information System (INIS)

    Zhang, Zhi-Xin; Liu, Zhi-Qiang; Jiang, Biao; Lu, Xin-Yang; Ning, Xiao-Fei; Yuan, Chuan-Tao; Wang, Ai-Liang

    2015-01-01

    Background and objective: Long non-coding RNA, BANCR, has been demonstrated to contribute to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer is still unknown. In present study, we investigated whether BANCR was involved in the development of gastric cancer cells via regulation of NF-κB1. Methods: Human gastric cancer tissues were isolated as well as human gastric cell lines MGC803 and BGC823 were cultured to investigate the role of BANCR in gastric cancer. Results: BANCR expression was significantly up-regulated in gastric tumor tissues and gastric cell lines. Down-regulation of BANCR inhibited gastric cancer cell growth and promoted cell apoptosis, and it also contributed to a significant decrease of NF-κB1 (P50/105) expression and 3′UTR of NF-κB1 activity. Overexpression of NF-κB1 reversed the effect of BANCR on cancer cell growth and apoptosis. MiroRNA-9 (miR-9) targeted NF-κB1, and miR-9 inhibitor also reversed the effects of BANCR on gastric cancer cell growth and apoptosis. Conclusion: BANCR was highly expressed both in gastric tumor tissues and in cancer cells. NF-κB1 and miR-9 were involved in the role of BANCR in gastric cancer cell growth and apoptosis. - Highlights: • BANCR up-regulated in gastric cancer (GC) tissues and cell lines MGC803 and BGC823. • Down-regulation of BANCR inhibited GC cell growth and promoted cell apoptosis. • Down-regulation of BANCR contributed to decreased 3′UTR of NF-κB1 and its expression. • Overexpressed NF-κB1 reversed the effect of BANCR on GC cell growth. • miR-9 inhibitor reversed the effect of BANCR on cancer GC cell growth

  3. On a generalization of B1( ) on C∗ -algebras

    Indian Academy of Sciences (India)

    Introduction. Let Ж be a complex and separable Hilbert space and let 多 (Ж ) be the set of bounded linear operators on Ж . Let be a open connected subset of complex plane C. A class of Cowen–Douglas operator with index one: B1( ) is defined as follows [6]: B1( ) =: {T ∈ 多 (Ж ): (i). ⊂ σ (T ) =: {λ ∈ C : T − λI is not invertible ...

  4. 26 CFR 31.3401(b)-1 - Payroll period.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Payroll period. 31.3401(b)-1 Section 31.3401(b... Collection of Income Tax at Source § 31.3401(b)-1 Payroll period. (a) The term payroll period means the... elapsed and receives the remainder at the end of the week, the payroll period is still the calendar week...

  5. 77 FR 46413 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-08-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-29] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...-$131.7M-15Jun10 FMS case ZUM-$32.1M-15Jun10 FMS case ULU-$150.3M-20Oct10 (vi) Sales Commission, Fee...

  6. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI Attenuates Elastase-Induced Emphysema in Mice

    Directory of Open Access Journals (Sweden)

    Bruno Tadeu Martins-Olivera

    2016-01-01

    Full Text Available Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD. However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group or saline (SAL group and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups. At day 28, the following analyses were performed: (I lung mechanics, (II exhaled nitric oxide (ENO, (III bronchoalveolar lavage fluid (BALF, and (IV lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

  7. Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells.

    Science.gov (United States)

    Kryza, Thomas; Silva, Lakmali M; Bock, Nathalie; Fuhrman-Luck, Ruth A; Stephens, Carson R; Gao, Jin; Samaratunga, Hema; Lawrence, Mitchell G; Hooper, John D; Dong, Ying; Risbridger, Gail P; Clements, Judith A

    2017-10-01

    The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line, including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease-activated receptor-1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient-derived CAFs compared to matched nonmalignant fibroblasts and were further increased by KLK4 treatment. Taken together, we propose that epithelial-derived KLK4 promotes tumour progression by actively promoting CAF differentiation in the prostate stromal microenvironment. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  8. Disruption of CTCF at the miR-125b1 locus in gynecological cancers

    International Nuclear Information System (INIS)

    Soto-Reyes, Ernesto; Herrera, Luis A; González-Barrios, Rodrigo; Cisneros-Soberanis, Fernanda; Herrera-Goepfert, Roberto; Pérez, Víctor; Cantú, David; Prada, Diddier; Castro, Clementina; Recillas-Targa, Félix

    2012-01-01

    In cancer cells, transcriptional gene silencing has been associated with genetic and epigenetic defects. The disruption of DNA methylation patterns and covalent histone marks has been associated with cancer development. Until recently, microRNA (miRNA) gene silencing was not well understood. In particular, miR-125b1 has been suggested to be an miRNA with tumor suppressor activity, and it has been shown to be deregulated in various human cancers. In the present study, we evaluated the DNA methylation at the CpG island proximal to the transcription start site of miR-125b1 in cancer cell lines as well as in normal tissues and gynecological tumor samples. In addition, we analyzed the association of CTCF and covalent histone modifications at the miR-125b1 locus. To assess the DNA methylation status of the miR-125b1, genomic DNA was transformed with sodium bisulfite, and then PCR-amplified with modified primers and sequenced. The miR-125b1 gene expression was analyzed by qRT-PCR using U6 as a control for constitutive gene expression. CTCF repressive histone marks abundance was evaluated by chromatin immunoprecipitation assays. The disruption of CTCF in breast cancer cells correlated with the incorporation of repressive histone marks such H3K9me3 and H3K27me3 as well as with aberrant DNA methylation patterns. To determine the effect of DNA methylation at the CpG island of miR-125b1 on the expression of this gene, we performed a qRT-PCR assay. We observed a significant reduction on the expression of miR-125b1 in cancer cells in comparison with controls, suggesting that DNA methylation at the CpG island might reduce miR-125b1 expression. These effects were observed in other gynecological cancers, including ovarian and cervical tumors. A reduction of miR-125b1 expression in cancers, correlated with methylation, repressive histone marks and loss of CTCF binding at the promoter region

  9. Novel kinin B1 receptor agonists with improved pharmacological profiles.

    Science.gov (United States)

    Côté, Jérôme; Savard, Martin; Bovenzi, Veronica; Bélanger, Simon; Morin, Josée; Neugebauer, Witold; Larouche, Annie; Dubuc, Céléna; Gobeil, Fernand

    2009-04-01

    There is some evidence to suggest that inducible kinin B1 receptors (B1R) may play beneficial and protecting roles in cardiovascular-related pathologies such as hypertension, diabetes, and ischemic organ diseases. Peptide B1R agonists bearing optimized pharmacological features (high potency, selectivity and stability toward proteolysis) hold promise as valuable therapeutic agents in the treatment of these diseases. In the present study, we used solid-phase methodology to synthesize a series of novel peptide analogues based on the sequence of Sar[dPhe(8)]desArg(9)-bradykinin, a relatively stable peptide agonist with moderate affinity for the human B1R. We evaluated the pharmacological properties of these peptides using (1) in vitro competitive binding experiments on recombinant human B1R and B2R (for index of selectivity determination) in transiently transfected human embryonic kidney 293 cells (HEK-293T cells), (2) ex vivo vasomotor assays on isolated human umbilical veins expressing endogenous human B1R, and (3) in vivo blood pressure tests using anesthetized lipopolysaccharide-immunostimulated rabbits. Key chemical modifications at the N-terminus, the positions 3 and 5 on Sar[dPhe(8)]desArg(9)-bradykinin led to potent analogues. For example, peptides 18 (SarLys[Hyp(3),Cha(5), dPhe(8)]desArg(9)-bradykinin) and 20 (SarLys[Hyp(3),Igl(5), dPhe(8)]desArg(9)-bradykinin) outperformed the parental molecule in terms of affinity, functional potency and duration of action in vitro and in vivo. These selective agonists should be valuable in future animal and human studies to investigate the potential benefits of B1R activation.

  10. Glaucoma and Cytochrome P4501B1 Gene Mutations

    Directory of Open Access Journals (Sweden)

    Mukesh Tanwar

    2010-01-01

    Full Text Available Developmental anomalies of the ocular anterior chamber angle may lead to an incomplete development of the structures that form the conventional aqueous outflow pathway. Thus, disorders that present with such dysfunction tend to be associated with glaucoma. Among them, Axenfeld-Rieger (ARS malformation is a rare clinical entity with an estimated prevalence of one in every 200,000 individuals. The changes in eye morphogenesis in ARS are highly penetrant and are associated with 50% risk of development of glaucoma. Mutations in the cytochrome P4501B1 (CYP1B1 gene have been reported to be associated with primary congenital glaucoma and other forms of glaucoma and mutations in pituitary homeobox 2 (PITX2 gene have been identified in ARS in various studies. This case was negative for PITX2 mutations and compound heterozygote for CYP1B1 mutations. Clinical manifestations of this patient include bilateral elevated intraocular pressure (>40 mmHg with increased corneal diameter (>14 mm and corneal opacity. Patient also had iridocorneal adhesions, anteriorly displaced Schwalbe line, anterior insertion of iris, broad nasal bridge and protruding umbilicus. This is the first study from north India reporting CYP1B1 mutations in Axenfeld-Rieger syndrome with bilateral buphthalmos and early onset glaucoma. Result of this study supports the role of CYP1B1 as a causative gene in ASD disorders and its role in oculogenesis.

  11. B1 gradient coherence selection using a tapered stripline.

    Science.gov (United States)

    van Meerten, S G J; Tijssen, K C H; van Bentum, P J M; Kentgens, A P M

    2018-01-01

    Pulsed-field gradients are common in modern liquid state NMR pulse sequences. They are often used instead of phase cycles for the selection of coherence pathways, thereby decreasing the time required for the NMR experiment. Soft off-resonance pulses with a B 1 gradient result in a spatial encoding similar to that created by pulsed-field (B 0 ) gradients. In this manuscript we show that pulse sequences with pulsed-field gradients can easily be converted to one which uses off-resonance B 1 field gradient (OFFBEAT) pulses. The advantage of B 1 gradient pulses for coherence selection is that the chemical shift evolution during the pulses is (partially) suppressed. Therefore no refocusing echos are required to correct for evolution during the gradient pulses. A tapered stripline is shown to be a convenient tool for creating a well-defined gradient in the B 1 field strength. B 1 gradient coherence selection using a tapered stripline is a simple and cheap alternative to B 0 pulsed-field gradients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Evaluation of B1 inhomogeneity effect on DCE-MRI data analysis of brain tumor patients at 3T.

    Science.gov (United States)

    Sengupta, Anirban; Gupta, Rakesh Kumar; Singh, Anup

    2017-12-02

    Dynamic-contrast-enhanced (DCE) MRI data acquired using gradient echo based sequences is affected by errors in flip angle (FA) due to transmit B 1 inhomogeneity (B 1 inh). The purpose of the study was to evaluate the effect of B 1 inh on quantitative analysis of DCE-MRI data of human brain tumor patients and to evaluate the clinical significance of B 1 inh correction of perfusion parameters (PPs) on tumor grading. An MRI study was conducted on 35 glioma patients at 3T. The patients had histologically confirmed glioma with 23 high-grade (HG) and 12 low-grade (LG). Data for B 1 -mapping, T 1 -mapping and DCE-MRI were acquired. Relative B 1 maps (B 1rel ) were generated using the saturated-double-angle method. T 1 -maps were computed using the variable flip-angle method. Post-processing was performed for conversion of signal-intensity time (S(t)) curve to concentration-time (C(t)) curve followed by tracer kinetic analysis (K trans , Ve, Vp, Kep) and first pass analysis (CBV, CBF) using the general tracer-kinetic model. DCE-MRI data was analyzed without and with B 1 inh correction and errors in PPs were computed. Receiver-operating-characteristic (ROC) analysis was performed on HG and LG patients. Simulations were carried out to understand the effect of B 1 inhomogeneity on DCE-MRI data analysis in a systematic way. S(t) curves mimicking those in tumor tissue, were generated and FA errors were introduced followed by error analysis of PPs. Dependence of FA-based errors on the concentration of contrast agent and on the duration of DCE-MRI data was also studied. Simulations were also done to obtain K trans of glioma patients at different B 1rel values and see whether grading is affected or not. Current study shows that B 1rel value higher than nominal results in an overestimation of C(t) curves as well as derived PPs and vice versa. Moreover, at same B 1rel values, errors were large for larger values of C(t). Simulation results showed that grade of patients can change

  13. Extrahepatic disposition of 3H-aflatoxin B1 in the rainbow trout (Oncorhynchus mykiss)

    International Nuclear Information System (INIS)

    Larsson, P.; Tjaelve, H.; Ngethe, S.; Ingebrigtsen, K.

    1992-01-01

    Whole-body autoradiography in rainbow trout (Oncorhynchus mykiss) after oral and intravenous administration of 3 H-labelled aflation B 1 showed labelling of several extrahepatic tissues, such as the uveal melanin and the vitreous humour of the eyes, the trunk and head kidney, the olfactory rosettes and the pyloric caecae. Liquid chromatography of extracts of the vitreous humour showed that unmetabolized 3 H-AFB 1 was the main labelled material present at this site. Liquid chromatography of extracts of the uveal melanin showed presence of aflatoxicol and aflatoxin B 1 in proportions of about 3:1. The binding to the pigment is probably due to a hydrophobic type of interaction with the melanin. Microautoradiography showed that melanin-containing cells in the trunk and head kidney and in the olfactory rosettes also accumulated high amounts of radioactivity. In the trunk kidney there was, in addition, a labelling of the second segment of the proximal tubules and of the distal tubules and the collecting ducts. Studies in vitro with microsomal and 12,000xg supernatant preparations of the trunk kidney showed formation of DNA- and protein-bound metabolites from the aflatoxin B 1 . It is probable that the bioactivation of the aflatoxin B 1 is confined to the second segment of the proximal tubules. The labelling of the distal tubules and the collecting ducts, which was confined to the cytoplasm of the cells, may be related to excretion and/or absorption processes. Microautoradiography of the olfactory rosettes, showed labelling of the sensory epithelium, but not the indifferent epithelium. A low formation of protein-bound aflatoxin B 1 -metabolites was found in incubations with microsomal preparations of this tissue. The same observation was made in incubations with microsomal preparations of the head kidney. In the pyloric caeca bound metabolites were observed in vivo at a level comparable to that found in the trunk kidney. Our results suggest that retention and metabolism

  14. Labelling aflatoxine-B1 by radioactive iodine

    International Nuclear Information System (INIS)

    Kim, Y.S.; Park, K.B.; Sung, H.K.; Ryu, Y.W.

    1977-01-01

    Labelling aflatoxines, the potential carcinogenic compounds, by radioactive iodine has been studied. The auflatoxine-B 1 , which is known to be the most abundant components of auflatoxines in the nature, was labelled by radioactive iodine-125 through an acid catalyst chloroamine-T procedure. The radiochemical yield was amounted to 63.6%. The chemical structure of the labelled product was proved to be 6-iodo 5-methoxy coumarine structure of auflatoxine-B 1 molecule by means of I.R. and N.M.R. spectroscopy. The labelled product was orally administered in a test animal (rat) and examined the accumulation of radioactivity in the body at the definite time interval. The accumulation of the radioactivity was pronounced at the blood and the liver. There was no indication of the decomposition of auflatoxine-B 1 - 125 I in the organs of the test animal. (author)

  15. Seasonal behaviour of B0 and B1

    International Nuclear Information System (INIS)

    Mosert Gonzalez, M. de; Radicella, S.M.

    1997-01-01

    A preliminary analysis of the thickness parameter B0 and the shape parameter B1 is presented. Noon electron density profiles recorded at five ionospheric stations during different seasonal and solar activity conditions are used in the study. The results show that both parameters present a seasonal trend with minimum value for B0 during the local winter and maximum during the local summer. This behaviour is inverted for B1. Discrepancies with IRI-90 model are found. (author). 8 refs, 4 figs, 2 tabs

  16. Variability in equatorial B0 and B1

    International Nuclear Information System (INIS)

    Adeniyi, J.O.; Radicella, S.M.

    2002-01-01

    Variability of ionospheric profile parameters B0 and B1, below the F2 peak is investigated for an equatorial station at two levels of solar activities. The whole 24 hours of the day and the four seasons of the year are covered. Absolute and relative variability indices were utilized in the study. Some evidences of correlations of variability index and profiles parameters were observed. Daytime values of relative variability in B1 at solar minimum were found to be greater than those of solar maximum. (author)

  17. RIA determination of aflatoxin B1 in food

    International Nuclear Information System (INIS)

    Bludovsky, R.

    1986-01-01

    The possibility was tested of the application of a commercial RIA kit in determining aflatoxin B 1 in foodstuffs. Stability, sensitivity, specificity and the effect of interfering materials were studied. Alternative methods were tested of sample preparation and a technique was proposed usable for food analysis. The kit was found to be mainly suitable for screening and for the determination of aflatoxin B 1 in concentrations exceedings 1 μg/kg. Lipids were found to cause a systematic positive error and should thus be removed by extraction prior to analysis. (author). 10 tabs., 15 refs

  18. A four-kallikrein panel for the prediction of repeat prostate biopsy: data from the European Randomized Study of Prostate Cancer screening in Rotterdam, Netherlands.

    Science.gov (United States)

    Gupta, A; Roobol, M J; Savage, C J; Peltola, M; Pettersson, K; Scardino, P T; Vickers, A J; Schröder, F H; Lilja, H

    2010-08-24

    Most men with elevated levels of prostate-specific antigen (PSA) do not have prostate cancer, leading to a large number of unnecessary biopsies. A statistical model based on a panel of four kallikreins has been shown to predict the outcome of a first prostate biopsy. In this study, we apply the model to an independent data set of men with previous negative biopsy but persistently elevated PSA. The study cohort consisted of 925 men with a previous negative prostate biopsy and elevated PSA (>or=3 ng ml(-1)), with 110 prostate cancers detected (12%). A previously published statistical model was applied, with recalibration to reflect the lower positive biopsy rates on rebiopsy. The full-kallikrein panel had higher discriminative accuracy than PSA and DRE alone, with area under the curve (AUC) improving from 0.58 (95% confidence interval (CI): 0.52, 0.64) to 0.68 (95% CI: 0.62, 0.74), Por=7) at biopsy with AUC improving from 0.76 (95% CI: 0.64, 0.89) to 0.87 (95% CI: 0.81, 0.94), P=0.003). Application of the panel to 1000 men with persistently elevated PSA after initial negative biopsy, at a 15% risk threshold would reduce the number of biopsies by 712; would miss (or delay) the diagnosis of 53 cancers, of which only 3 would be Gleason 7 and the rest Gleason 6 or less. Our data constitute an external validation of a previously published model. The four-kallikrein panel predicts the result of repeat prostate biopsy in men with elevated PSA while dramatically decreasing unnecessary biopsies.

  19. Osmotic stress upregulates the transcription of thiamine (vitamin B1 ...

    African Journals Online (AJOL)

    Syamimi Mimi

    2016-07-20

    Jul 20, 2016 ... damage tolerance when subjected to abiotic stress. (Machado et al. ... µg/µl of total RNA, 4 µl of 5× Reverse Transcriptase Buffer, 1 µl of 10 mM ..... facilitate vitamin B1 biofortification of plants by genetic engineering;. Front.

  20. 26 CFR 1.167(b)-1 - Straight line method.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Straight line method. 1.167(b)-1 Section 1.167(b... Straight line method. (a) In general. Under the straight line method the cost or other basis of the... may be reduced to a percentage or fraction. The straight line method may be used in determining a...

  1. 26 CFR 1.269B-1 - Stapled foreign corporations.

    Science.gov (United States)

    2010-04-01

    ... avoidance of U.S. income tax. A stapling of interests may have a principal purpose of tax avoidance even though the tax avoidance purpose is outweighed by other purposes when taken together. (3) Example. The....269B-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX...

  2. 77 FR 68742 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-11-16

    ... missile defense capability, strengthen its homeland defense, and deter regional threats. The proposed sale... Defense System continues to hold a significant technology lead over other surface-to-air missile systems... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-58] 36(b)(1) Arms Sales...

  3. 78 FR 48426 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-08-08

    ... of Technology: 1. The AN/FPS-132 Block 5 supports Missile Defense, Space Situational Awareness, and... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-33] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The...

  4. 77 FR 40028 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-07-06

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-18] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The... proposed sale will require travel of U.S. Government or contractor representatives to Kuwait on a temporary...

  5. 78 FR 26332 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2013-05-06

    ... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... type of mission. 2. The AN/ALE-47 Counter-Measures Dispensing System (CMDS) is an integrated, threat... multiple Optical Sensor Converter (OSC) units, a Computer Processor (CP) and a Control Indicator (CI). The...

  6. 77 FR 27202 - 36(b)(1) Arms Sales Notification

    Science.gov (United States)

    2012-05-09

    ... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This... airframe/outer mold line, Pratt and Whitney engine, radar, integrated core processor central computer... amounts and types of stores, fuel, and other supplies or equipment needed to quickly turn the aircraft for...

  7. 75 FR 41820 - 36(b)(1) Arms Sales Notifications

    Science.gov (United States)

    2010-07-19

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-05, 10-11, 10-18, 10-21 and 10-29] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION...) arms sales notifications to fulfill the requirements of section 155 of Public Law 104-164, dated 21...

  8. Mycoplasma hyopneumoniae in vitro peptidase activities: identification and cleavage of kallikrein-kinin system-like substrates.

    Science.gov (United States)

    Moitinho-Silva, Lucas; Kondo, Marcia Y; Oliveira, Lilian C G; Okamoto, Debora N; Paes, Jéssica A; Machado, Mauricio F M; Veronez, Camila L; Motta, Guacyara; Andrade, Sheila S; Juliano, Maria A; Ferreira, Henrique B; Juliano, Luiz; Gouvea, Iuri E

    2013-05-03

    Bacterial proteases are important for metabolic processes and pathogenesis in host organisms. The bacterial swine pathogen Mycoplasma hyopneumoniae has 15 putative protease-encoding genes annotated, but none of them have been functionally characterized. To identify and characterize peptidases that could be relevant for infection of swine hosts, we investigated the peptidase activity present in the pathogenic 7448 strain of M. hyopneumoniae. Combinatorial libraries of fluorescence resonance energy transfer peptides, specific inhibitors and pH profiling were used to screen and characterize endopeptidase, aminopeptidase and carboxypeptidase activities in cell lysates. One metalloendopeptidase, one serine endopeptidase, and one aminopeptidase were detected. The detected metalloendopeptidase activity, prominent at neutral and basic pH ranges, was due to a thimet oligopeptidase family member (M3 family), likely an oligoendopeptidase F (PepF), which cleaved the peptide Abz-GFSPFRQ-EDDnp at the F-S bond. A chymotrypsin-like serine endopeptidase activity, possibly a subtilisin-like serine protease, was prominent at higher pH levels, and was characterized by its preference for a Phe residue at the P1 position of the substrate. The aminopeptidase P (APP) activity showed a similar profile to that of human membrane-bound APP. Genes coding for these three peptidases were identified and their transcription was confirmed in the 7448 strain. Furthermore, M. hyopneumoniae cell lysate peptidases showed effects on kallikrein-kinin system-like substrates, such as bradykinin-derived substrates and human high molecular weight kininogen. The M. hyopneumoniae peptidase activities, here characterized for the first time, may be important for bacterial survival strategies and thus represent possible targets for drug development against M. hyopneumoniae swine infections. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Gene Directed Enzyme Prodrug Therapy Using Rabbit Cytochrome P450 4B1 in Murine Colon Adenocarcinoma

    International Nuclear Information System (INIS)

    Kim, Sung Joo; Kang, Joo Hyun; Lee, Tae Sup; Kim, Kyeong Min; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

    2007-01-01

    The conventional cancer therapy is chemotherapy, surgical resection and/or radiotherapy. Chemotherapy using cytotoxic drug has some problems with lack of tumor selectivity resulting in toxicity to normal tissues. To enhance the tumor selectivity of cytotoxic drug, the application of suicidal gene therapy technology was designed. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a non-toxic prodrug into a cytotoxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1- tk) and cytosine deaminase (cd). Recently, a new prodrug-converting enzyme based on rabbit cytochrome P450 4B1 gene (cyp4B1) has been reported for therapy of experimental brain tumor. This enzyme activates the prodrugs such as 4-ipomeanol (4-IM) and 2- aminoanthracene (2-AA) to highly reactive furane epoxide and unsaturated dialdehyde intermediate, respectively. DNA alkylation seems to be the main mechanism of cytotoxicity of these activated drugs. In this study, we isolated cyp4B1 cDNA from rabbit lung, transduced cyp4B1 expression vector into murine colon cancer cell, and then analyzed the cytotoxic properties of cyp4b1-activated 2-AA in cyp4B1 transduced cells to verify the cyp4B1 enzyme system for gene directed enzyme prodrug therapy

  10. Gene Directed Enzyme Prodrug Therapy Using Rabbit Cytochrome P450 4B1 in Murine Colon Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Joo; Kang, Joo Hyun; Lee, Tae Sup; Kim, Kyeong Min; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2007-07-01

    The conventional cancer therapy is chemotherapy, surgical resection and/or radiotherapy. Chemotherapy using cytotoxic drug has some problems with lack of tumor selectivity resulting in toxicity to normal tissues. To enhance the tumor selectivity of cytotoxic drug, the application of suicidal gene therapy technology was designed. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a non-toxic prodrug into a cytotoxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1- tk) and cytosine deaminase (cd). Recently, a new prodrug-converting enzyme based on rabbit cytochrome P450 4B1 gene (cyp4B1) has been reported for therapy of experimental brain tumor. This enzyme activates the prodrugs such as 4-ipomeanol (4-IM) and 2- aminoanthracene (2-AA) to highly reactive furane epoxide and unsaturated dialdehyde intermediate, respectively. DNA alkylation seems to be the main mechanism of cytotoxicity of these activated drugs. In this study, we isolated cyp4B1 cDNA from rabbit lung, transduced cyp4B1 expression vector into murine colon cancer cell, and then analyzed the cytotoxic properties of cyp4b1-activated 2-AA in cyp4B1 transduced cells to verify the cyp4B1 enzyme system for gene directed enzyme prodrug therapy.

  11. Human umbilical vein: involvement of cyclooxygenase-2 pathway in bradykinin B1 receptor-sensitized responses.

    Science.gov (United States)

    Errasti, A E; Rey-Ares, V; Daray, F M; Rogines-Velo, M P; Sardi, S P; Paz, C; Podestá, E J; Rothlin, R P

    2001-08-01

    In isolated human umbilical vein (HUV), the contractile response to des-Arg9-bradykinin (des-Arg9-BK), selective BK B1 receptor agonist, increases as a function of the incubation time. Here, we evaluated whether cyclooxygenase (COX) pathway is involved in BK B1-sensitized response obtained in 5-h incubated HUV rings. The effect of different concentrations of indomethacin, sodium salicylate, ibuprofen, meloxicam, lysine clonixinate or NS-398 administrated 30 min before concentration-response curves (CRC) was studied. All treatments produced a significant rightward shift of the CRC to des-Arg9-BK in a concentration-dependent manner, which provides pharmacological evidence that COX pathway is involved in the BK B1 responses. Moreover, in this tissue, the NS-398 pKb (5.2) observed suggests that COX-2 pathway is the most relevant. The strong correlation between published pIC50 for COX-2 and the NSAIDs' pKbs estimated further supports the hypothesis that COX-2 metabolites are involved in BK B1 receptor-mediated responses. In other rings, indomethacin (30, 100 micromol/l) or NS-398 (10, 30 micromol/l) produced a significant rightward shift of the CRC to BK, selective BK B2 agonist, and its pKbs were similar to the values to inhibit BK B1 receptor responses, suggesting that COX-2 pathway also is involved in BK B2 receptor responses. Western blot analysis shows that COX-1 and COX-2 isoenzymes are present before and after 5-h in vitro incubation and apparently COX-2 does not suffer additional induction.

  12. Non-linear relationships between aflatoxin B1 levels and the biological response of monkey kidney vero cells

    Science.gov (United States)

    Aflatoxin (AF)-producing fungi contaminate food and feed during preharvest, storage and processing periods. Once consumed, AF accumulates in tissues, causing illnesses in animals and humans. At least 20 different types of AFs have been identified, and of these, aflatoxin B1 (AFB1) is the most ubiqui...

  13. Skin barrier disruption by sodium lauryl sulfate-exposure alters the expressions of involucrin, transglutaminase 1, profilaggrin, and kallikreins during the repair phase in human skin in vivo.

    Science.gov (United States)

    Törmä, Hans; Lindberg, Magnus; Berne, Berit

    2008-05-01

    Detergents are skin irritants affecting keratinocytes. In this study, healthy volunteers were exposed to water (vehicle) and 1% sodium lauryl sulfate (SLS) under occlusive patch tests for 24 hours. The messenger RNA (mRNA) expression of keratinocyte differentiation markers and of enzymes involved in corneodesmosome degradation was examined in skin biopsies (n=8) during the repair phase (6 hours to 7 days postexposure) using real-time reverse-transcription PCR. It was found that the expression of involucrin was increased at 6 hours, but then rapidly normalized. The expression of transglutaminase 1 exhibited a twofold increase after 24 hours in the SLS-exposed skin. Profilaggrin was decreased after 6 hours. Later (4-7 days), the expression in SLS-exposed areas was >50% above than in control areas. An increased and altered immunofluorescence pattern of involucrin, transglutaminase 1, and filaggrin was also found (n=4). At 6 hours post-SLS exposure, the mRNA expression of kallikrein-7 (KLK-7) and kallikrein-5 (KLK-5) was decreased by 50 and 75%, respectively, as compared with control and water-exposed areas. Thereafter, the expression pattern of KLK-7 and KLK-5 was normalized. Changes in protein expression of KLK-5 were also found. In conclusion, SLS-induced skin barrier defects induce altered mRNA expression of keratinocyte differentiation markers and enzymes degrading corneodesmosomes.

  14. 26 CFR 1.367(b)-1 - Other transfers.

    Science.gov (United States)

    2010-04-01

    ... its successor in interest) that the shareholder is making the election described in § 1.367(b)-3(c)(3... paragraph (c)(2)— (i) A shareholder described in § 1.367(b)-3(b)(1) that realizes income in a transaction described in § 1.367(b)-3(a); (ii) A shareholder that makes the election described in § 1.367(b)-3(c)(3...

  15. CobB1 deacetylase activity in Streptomyces coelicolor

    Czech Academy of Sciences Publication Activity Database

    Mikulík, Karel; Felsberg, Jürgen; Kudrnáčová, E.; Bezoušková, Silvia; Šetinová, Dita; Stodůlková, Eva; Zídková, J.; Zídek, Václav

    2012-01-01

    Roč. 90, č. 2 (2012), s. 179-187 ISSN 0829-8211 R&D Projects: GA AV ČR(CZ) IAA500110805; GA ČR GA303/09/0475 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z50200510 Keywords : sirtuin * NAD(+)dependent deacetylation activity CobB1 * Streptomyces coeliocolor Subject RIV: EE - Microbiology, Virology Impact factor: 2.915, year: 2012

  16. Biochemical characterization of the GM2 gangliosidosis B1 variant

    Directory of Open Access Journals (Sweden)

    Tutor J.C.

    2004-01-01

    Full Text Available The deficiency of the A isoenzyme of ß-hexosaminidase (Hex produced by different mutations of the gene that codes for the alpha subunit (Tay-Sachs disease has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic alpha subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-ß-D-glucosaminide, may offer a valid alternative. The presence of an alpha subunit in the alphaß heterodimer Hex A means that its activation energy (41.8 kJ/mol is significantly lower than that of the ßß homodimer Hex B (75.1 kJ/mol; however, as mutation inactivates the alpha subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme.

  17. Wind tunel tests of Risoe-B1-18 and Risoe-B1-24

    Energy Technology Data Exchange (ETDEWEB)

    Fuglsang, P.; Bak, C.; Gaunaa, M.; Antoniou, I.

    2003-01-01

    This report contains 2D measurements of the Risoe-B1-18 and Risoe-B1-24 airfoils. The aerodynamic properties were derived from pressure measurements on the airfoil surface and in the wake. The measurements were conducted in the VELUX open jet wind tunnel, which has a background turbulence intensity of 1%, and an inlet flow velocity of 42 m/s. The airfoil sections had a chord of 0.600 m giving a Reynolds number of 1.6Oe106. The span was 1.9 m and end plates were used to minimize 3D flow effects. The measurements comprised both static and dynamic inflow. Static inflow covered angles of attack from 5o to 30 deg. Dynamic inflow was obtained by pitching the airfoil in a harmonic motion around various mean angles of attack. The test matrix involved smooth flow, various kinds of leading edge roughness, stall strips, vortex generators and Gurney flaps in different combinations. The quality of the measurements was good and the agreement between measurements and numerical CFD predictions with EllipSys2D was good. For both airfoils predictions with turbulent flow captured very well the shapes of lift and drag curves as well as the magnitude of maximum lift. Measurements of Risoe-B1-18 showed that the maximum lift coefficient was 1.64 at an angle of attack of approximately 13 deg. The airfoil was not very sensitive to leading edge roughness despite its high maximum lift. Measurements with stall strips showed that stall strips could control the level of maximum lift. The Risoe-B1-24 measurements showed that the maximum lift coefficient was 1.62 at an angle of attack of approximately 14 deg. The airfoil was only little sensitive to leading edge roughness despite its high relative thickness and high maximum lift. Measurements with delta wing shaped vortex generators increased the maximum lift coefficient to 2.02 and measurements with Gurney flaps increased the maximum lift coefficient to 1.85. Measurements with combination of vortex generators and Gurney flaps showed a maximum

  18. Cloning and tissue expression of cytochrome P450 1B1 and 1C1 ...

    African Journals Online (AJOL)

    SAM

    2014-05-14

    May 14, 2014 ... lower eukaryotes and bacteria(Bernhardt, 2006; Nebert and Dalton, 2006 ... response testing and sensitive molecular biomarkers testing (Koyama et al. .... chlorinated, and aerated several days prior to its use in the salinity.

  19. Calcium Homeostasis and Muscle Energy Metabolism Are Modified in HspB1-Null Mice

    Directory of Open Access Journals (Sweden)

    Brigitte Picard

    2016-05-01

    Full Text Available Hsp27—encoded by HspB1—is a member of the small heat shock proteins (sHsp, 12–43 kDa (kilodalton family. This protein is constitutively present in a wide variety of tissues and in many cell lines. The abundance of Hsp27 is highest in skeletal muscle, indicating a crucial role for muscle physiology. The protein identified as a beef tenderness biomarker was found at a crucial hub in a functional network involved in beef tenderness. The aim of this study was to analyze the proteins impacted by the targeted invalidation of HspB1 in the Tibialis anterior muscle of the mouse. Comparative proteomics using two-dimensional gel electrophoresis revealed 22 spots that were differentially abundant between HspB1-null mice and their controls that could be identified by mass spectrometry. Eighteen spots were more abundant in the muscle of the mutant mice, and four were less abundant. The proteins impacted by the absence of Hsp27 belonged mainly to calcium homeostasis (Srl and Calsq1, contraction (TnnT3, energy metabolism (Tpi1, Mdh1, PdhB, Ckm, Pygm, ApoA1 and the Hsp proteins family (HspA9. These data suggest a crucial role for these proteins in meat tenderization. The information gained by this study could also be helpful to predict the side effects of Hsp27 depletion in muscle development and pathologies linked to small Hsps.

  20. E3B1/ABI-1 Isoforms Are Down-Regulated in Cancers of Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Rafia A. Baba

    2012-01-01

    Full Text Available The expression of E3B1/ABI-1 protein and its role in cancer progression and prognosis are largely unknown in the majority of solid tumors. In this study, we examined the expression pattern of E3B1/ABI-1 protein in histologically confirmed cases of esophageal (squamous cell carcinoma and adenocarcinoma, gastro-esophageal junction, colorectal cancers and corresponding normal tissues freshly resected from a cohort of 135 patients, by Western Blotting and Immunofluorescence Staining. The protein is present in its phosphorylated form in cells and tissues. Depending on the extent of phosphorylation it is either present in hyper-phosphorylated (M. Wt. 72 kDa form or in hypo-phosphorylated form (M. Wt. 68 kDa and 65 kDa. A thorough analysis revealed that expression of E3B1/ABI-1 protein is significantly decreased in esophageal, gastro-esophageal junction and colorectal carcinomas irrespective of age, gender, dietary and smoking habits of the patients. The decrease in expression of E3B1/ABI-1 was consistently observed for all the three isoforms. However, the decrease in the expression of isoforms varied with different forms of cancers. Down-regulation of E3B1/ABI-1 expression in human carcinomas may play a critical role in tumor progression and in determining disease prognosis.

  1. Predictive value of four kallikrein markers for pathologically insignificant compared with aggressive prostate cancer in radical prostatectomy specimens: results from the European Randomized Study of Screening for Prostate Cancer section Rotterdam.

    Science.gov (United States)

    Carlsson, Sigrid; Maschino, Alexandra; Schröder, Fritz; Bangma, Chris; Steyerberg, Ewout W; van der Kwast, Theo; van Leenders, Geert; Vickers, Andrew; Lilja, Hans; Roobol, Monique J

    2013-11-01

    Treatment decisions can be difficult in men with low-risk prostate cancer (PCa). To evaluate the ability of a panel of four kallikrein markers in blood-total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2-to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries. The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA ≥3.0 ng/ml and were treated with RP between 1994 and 2004. We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3-T4, extracapsular extension, tumor volume >0.5cm(3), or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood. A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model. Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  2. Experimental validation of hyperthermia SAR treatment planning using MR B1+ imaging

    International Nuclear Information System (INIS)

    Berg, Cornelis A T van den; Bartels, Lambertus W; Leeuw, Astrid A C De; Lagendijk, Jan J W; Kamer, Jeroen B Van de

    2004-01-01

    In this paper the concept of using B 1+ imaging as a means to validate SAR models for radiofrequency hyperthermia is presented. As in radiofrequency hyperthermia, in common clinical MR imaging which applies RF frequencies between 64 and 128 MHz, the RF field distribution inside a patient is largely determined by the dielectric distribution of the anatomy. Modern MR imaging techniques allow measurement of the RF magnetic field component B 1+ making it possible to measure at high resolution the dielectric interaction of the RF field with the patient. Given these considerations, we propose to use MR imaging to verify the validity of our dielectric patient model used for SAR models of radiofrequency hyperthermia. The aim of this study was to investigate the feasibility of this concept by performing B 1+ measurements and simulations on cylindrical split phantoms consisting of materials with dielectric properties similar to human tissue types. Important topics of investigation were the accuracy and sensitivity of B 1+ measurements and the validity of the electric model of the MR body coil. The measurements were performed on a clinical 1.5 T MR scanner with its quadrature body coil operating at 64 MHz. It was shown that even small B 1+ variations of 2 to 5% could be measured reliably in the phantom experiments. An electrical model of the transmit coil was implemented on our FDTD-based hyperthermia treatment planning platform and the RF field distributions were calculated assuming an idealized quadrature current distribution in the coil. A quantitatively good correlation between measurements and simulations was found for phantoms consisting of water and oil, while highly conductive phantoms show considerable deviations. However, assuming linear excitation for these conductive phantoms resulted in good correspondence. As an explanation it is suggested that the coil is being detuned due to the inductive nature of the conductive phantoms, breaking up the phase difference of

  3. A search for cyanopolyynes in L1157-B1

    Science.gov (United States)

    Mendoza, Edgar; Lefloch, B.; Ceccarelli, C.; Kahane, C.; Jaber, A. A.; Podio, L.; Benedettini, M.; Codella, C.; Viti, S.; Jimenez-Serra, I.; Lepine, J. R. D.; Boechat-Roberty, H. M.; Bachiller, R.

    2018-04-01

    We present here a systematic search for cyanopolyynes in the shock region L1157-B1 and its associated protostar L1157-mm in the framework of the Large Program`Astrochemical Surveys At IRAM' (ASAI), dedicated to chemical surveys of solar-type star-forming regions with the IRAM 30-m telescope. Observations of the millimeter windows between 72 and 272 GHz permitted the detection of HC3N and its 13C isotopologues, and HC5N (for the first time in a protostellar shock region). In the shock, the analysis of the line profiles shows that the emission arises from the outflow cavities associated with L1157-B1 and L1157-B2. Molecular abundances and excitation conditions were obtained from the analysis of the Spectral Line Energy Distributions under the assumption of Local Thermodynamical Equilibrium or using a radiative transfer code in the Large Velocity Gradient approximation. Towards L1157 mm, the HC3N emission arises from the cold envelope (T_rot=10K) and a higher-excitation region (Trot = 31K) of smaller extent around the protostar. We did not find any evidence of 13C or D fractionation enrichment towards L1157-B1. We obtain a relative abundance ratio HC3N/HC5N of 3.3 in the shocked gas. We find an increase by a factor of 30 of the HC3N abundance between the envelope of L1157-mm and the shock region itself. Altogether, these results are consistent with a scenario in which the bulk of HC3N was produced by means of gas phase reactions in the passage of the shock. This scenario is supported by the predictions of a parametric shock code coupled with the chemical model UCL_CHEM.

  4. EphrinB1/EphB3b Coordinate Bidirectional Epithelial-Mesenchymal Interactions Controlling Liver Morphogenesis and Laterality

    DEFF Research Database (Denmark)

    Cayuso, Jordi; Dzementsei, Aliaksandr; Fischer, Johanna C

    2016-01-01

    Positioning organs in the body often requires the movement of multiple tissues, yet the molecular and cellular mechanisms coordinating such movements are largely unknown. Here, we show that bidirectional signaling between EphrinB1 and EphB3b coordinates the movements of the hepatic endoderm...... and adjacent lateral plate mesoderm (LPM), resulting in asymmetric positioning of the zebrafish liver. EphrinB1 in hepatoblasts regulates directional migration and mediates interactions with the LPM, where EphB3b controls polarity and movement of the LPM. EphB3b in the LPM concomitantly repels hepatoblasts...

  5. Leptin induces CYP1B1 expression in MCF-7 cells through ligand-independent activation of the ERα pathway

    Energy Technology Data Exchange (ETDEWEB)

    Khanal, Tilak; Kim, Hyung Gyun; Do, Minh Truong; Choi, Jae Ho; Won, Seong Su [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of); Kang, Wonku [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Chung, Young Chul [Department of Food Science and Culinary, International University of Korea, Jinju (Korea, Republic of); Jeong, Tae Cheon, E-mail: taecheon@ynu.ac.kr [College of Pharmacy, Yeungnam University, Gyeongsan (Korea, Republic of); Jeong, Hye Gwang, E-mail: hgjeong@cnu.ac.kr [Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon (Korea, Republic of)

    2014-05-15

    Leptin, a hormone with multiple biological actions, is produced predominantly by adipose tissue. Among its functions, leptin can stimulate tumour cell growth. Oestrogen receptor α (ERα), which plays an essential role in breast cancer development, can be transcriptionally activated in a ligand-independent manner. In this study, we investigated the effect of leptin on CYP1B1 expression and its mechanism in breast cancer cells. Leptin induced CYP1B1 protein, messenger RNA expression and promoter activity in ERα-positive MCF-7 cells but not in ERα-negative MDA-MB-231 cells. Additionally, leptin increased 4-hydroxyoestradiol in MCF-7 cells. Also, ERα knockdown by siRNA significantly blocked the induction of CYP1B1 expression by leptin, indicating that leptin induced CYP1B1 expression via an ERα-dependent mechanism. Transient transfection with CYP1B1 deletion promoter constructs revealed that the oestrogen response element (ERE) plays important role in the up-regulation of CYP1B1 by leptin. Furthermore, leptin stimulated phosphorylation of ERα at serine residues 118 and 167 and increased ERE-luciferase activity, indicating that leptin induced CYP1B1 expression by ERα activation. Finally, we found that leptin activated ERK and Akt signalling pathways, which are upstream kinases related to ERα phosphorylation induced by leptin. Taken together, our results indicate that leptin-induced CYP1B1 expression is mediated by ligand-independent activation of the ERα pathway as a result of the activation of ERK and Akt in MCF-7 cells. - Highlights: • Leptin increased 4-hydroxyoestradiol in MCF-7 breast cancer cells. • Leptin activated ERK and Akt kinases related to ERα phosphorylation. • Leptin induces phosphorylation of ERα at serine residues 118 and 167. • Leptin induces ERE-luciferase activity.

  6. Synthesis of Polyclonal Antibodies against Aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Wiyogo Prio Wicaksono

    2015-09-01

    Full Text Available Polyclonal antibodies of aflatoxin B1 were successfully produced from New Zealand White female rabbits after immunization by the hapten of aflatoxin B1-carboxymethyl hydroxylamine hemihydrochloride (AFB1-CMO conjugated with bovine serum albumin (BSA as the antigen. The hapten was synthesized using the carbodiimide method with CMO as a linker. Absorption peaks at 362, 264, and 218 nm were observed as a result of characterization with UV-Vis spectroscopy, while IR spectroscopy showed peaks at 3448 cm-1 and 1642 cm-1 attributable to the hydroxyl and nitrile groups, respectively. Furthermore, mass spectrometry showed fragmentation at the m/z of 386, 368.2, and 310, which confirms that the hapten of AFB1-CMO was successfully synthesized. The hapten was then conjugated with BSA to serve as an antigen of AFB1 when it was injected into the rabbits. The specificity of the antigen towards its antibody and the confirmation of hapten-BSA conjugation were characterized using the dot blot immunoassay, which showed a BSA concentration of 1.74 mg/mL. Two weeks after the primary immunization by its antigen, agar gel precipitation testing showed that the rabbit blood serum had positive results for polyclonal antibodiest against AFB1 with the highest concentration of antibodiest of 2.19 mg/mL.

  7. Screening and Initial Binding Assessment of Fumonisin B1 Aptamers

    Directory of Open Access Journals (Sweden)

    Maria C. DeRosa

    2010-11-01

    Full Text Available Fumonisins are mycotoxins produced by Fusarium verticillioides and F. proliferatum, fungi that are ubiquitous in corn (maize. Insect damage and some other environmental conditions result in the accumulation of fumonisins in corn-based products worldwide. Current methods of fumonisin detection rely on the use of immunoaffinity columns and high-performance liquid chromatography (HPLC. The use of aptamers offers a good alternative to the use of antibodies in fumonisin cleanup and detection due to lower costs and improved stability. Aptamers are single-stranded oligonucleotides that are selected using Systematic Evolution of Ligands by EXponential enrichment (SELEX for their ability to bind to targets with high affinity and specificity. Sequences obtained after 18 rounds of SELEX were screened for their ability to bind to fumonisin B1. Six unique sequences were obtained, each showing improved binding to fumonisin B1 compared to controls. Sequence FB1 39 binds to fumonisin with a dissociation constant of 100 ± 30 nM and shows potential for use in fumonisin biosensors and solid phase extraction columns.

  8. Rapid Immunoenzyme Assay of Aflatoxin B1 Using Magnetic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Alexandr E. Urusov

    2014-11-01

    Full Text Available The main limitations of microplate-based enzyme immunoassays are the prolonged incubations necessary to facilitate heterogeneous interactions, the complex matrix and poorly soluble antigens, and the significant sample dilutions often required because of the presence of organic extractants. This study presents the use of antibody immobilization on the surface of magnetic particles to overcome these limitations in the detection of the mycotoxin, aflatoxin B1. Features of the proposed system are a high degree of nanoparticle dispersion and methodologically simple immobilization of the antibodies by adsorption. Reactions between the immobilized antibodies with native and labeled antigens are conducted in solution, thereby reducing the interaction period to 5 min without impairing the analytical outcome. Adsorption of immunoglobulins on the surface of magnetic nanoparticles increases their stability in aqueous-organic media, thus minimizing the degree of sample dilution required. Testing barley and maize extracts demonstrated a limit of aflatoxin B1 detection equal to 20 pg/mL and total assay duration of 20 min. Using this method, only the 3-fold dilution of the initial methanol/water (60/40 extraction mixture in the microplate wells is necessary. The proposed pseudo-homogeneous approach could be applied toward immunodetection of a wide range of compounds.

  9. DELF B1 200 activités

    CERN Document Server

    Bloomfield, Anatole

    2006-01-01

    L'ouvrage est organisé par compétences de réception et de production. Chaque partie propose d'abord une présentation de l'épreuve correspondante, puis les activités de préparation suivies d'épreuves-types et d'une auto-évaluation. Dans le cadre d'une approche actionnelle, les activités fournissent les outils nécessaires à la préparation des examens. Elles donnent des exemples concrets répondant aux attentes des candidats comme à celle des examinateurs. LeNouveau DELF B1 propose des activités précises en vue d'atteindre les compétences nécessaires aux épreuves (oral, écrit, réception, production); sa simplicité et sa pédagogie en font une méthode complète. Dans la tradition de la collection Nouvel Entraînez-vous, cet ouvrage est pratique, didactique et se prête à une utilisation en autonomie ou en classe.Le niveau B1 dit " avancé " évalue un niveau de compétence où l'apprenant peut se considérer comme étant indépendant. Arrivé à ce stade, il est apte de comprendre l'inform...

  10. Competition for vitamin B1 (thiamin) structures numerous ecological interactions.

    Science.gov (United States)

    Kraft, Clifford E; Angert, Esther R

    2017-06-01

    Thiamin (vitamin B1) is a cofactor required for essential biochemical reactions in all living organisms, yet free thiamin is scarce in the environment. The diversity of biochemical pathways involved in the acquisition, degradation, and synthesis of thiamin indicates that organisms have evolved numerous ecological strategies for meeting this nutritional requirement. In this review we synthesize information from multiple disciplines to show how the complex biochemistry of thiamin influences ecological outcomes of interactions between organisms in environments ranging from the open ocean and the Australian outback to the gastrointestinal tract of animals. We highlight population and ecosystem responses to the availability or absence of thiamin. These include widespread mortality of fishes, birds, and mammals, as well as the thiamin-dependent regulation of ocean productivity. Overall, we portray thiamin biochemistry as the foundation for molecularly mediated ecological interactions that influence survival and abundance of a vast array of organisms.

  11. Cytochrome P450 1b1 in polycyclic aromatic hydrocarbon (PAH)-induced skin carcinogenesis: Tumorigenicity of individual PAHs and coal-tar extract, DNA adduction and expression of select genes in the Cyp1b1 knockout mouse

    Energy Technology Data Exchange (ETDEWEB)

    Siddens, Lisbeth K. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Bunde, Kristi L. [College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Harper, Tod A. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); McQuistan, Tammie J. [Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); Löhr, Christiane V. [Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Bramer, Lisa M. [Applied Statistics and Computational Modeling, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Waters, Katrina M. [Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Tilton, Susan C. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Krueger, Sharon K. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); and others

    2015-09-01

    FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar extract (CTE, SRM 1597a). Following 20 weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity, and progression. None of these effects were observed with BaP or CTE. The mechanism of Cyp 1b1-dependent alteration of DBC skin carcinogenesis was further investigated by determining expression of select genes in skin from DBC-treated mice 2, 4 and 8 h post-initiation. A significant reduction in levels of Cyp 1a1, Nqo1 at 8 h and Akr 1c14 mRNA was observed in Cyp 1b1 null (but not wt or het) mice, whereas no impact was observed in Gst a1, Nqo 1 at 2 and 4 h or Akr 1c19 at any time point. Cyp 1b1 mRNA was not elevated by DBC. The major covalent DNA adducts, dibenzo[def,p]chrysene-(±)-11,12-dihydrodiol-cis and trans-13,14-epoxide-deoxyadenosine (DBCDE-dA) were quantified by UHPLC-MS/MS 8 h post-initiation. Loss of Cyp1 b1 expression reduced DBCDE-dA adducts in the skin but not to a statistically significant degree. The ratio of cis- to trans-DBCDE-dA adducts was higher in the skin than other target tissues such as the spleen, lung and liver (oral dosing). These results document that Cyp 1b1 plays a significant role in bioactivation and carcinogenesis of DBC in a two-stage mouse skin tumor model and that loss of Cyp 1b1 has little impact on tumor response with BaP or CTE as initiators. - Highlights: • Cyp1b1 null mice exhibit lower skin cancer sensitivity to DBC but not BaP or CTE. • Cyp1b1 expression impacts expression of other PAH metabolizing enzymes. • cis/trans-DBCDE-dA ratio significantly higher in the skin than the spleen, lung or liver • Potency of DBC and CTE in mouse skin is higher than predicted by RPFs.

  12. Down-regulation of HSP40 gene family following OCT4B1 suppression in human tumor cell lines

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Mirzaei

    2016-02-01

    Full Text Available Objective(s: The OCT4B1, as one of OCT4 variants, is expressed in cancer cell lines and tissues more than other variants and plays an important role in apoptosis and stress (heat shock protein pathways. The present study was designed to determine the effects of OCT4B1 silencing on expressional profile of HSP40 gene family expression in three different human tumor cell lines. Materials and Methods: The OCT4B1 expression was suppressed by specific siRNA transfection in AGS (gastric adenocarcinoma, 5637 (bladder tumor and U-87MG (brain tumor cell lines employing Lipofectamine reagent. Real-time PCR array technique was employed for RNA qualification. The fold changes were calculated using RT2 Profiler PCR array data analysis software version 3.5. Results: Our results indicated that fifteen genes (from 36 studied genes were down-regulated and two genes (DNAJC11 and DNAJC5B were up-regulated in all three studied tumor cell lines by approximately more than two folds. The result of other studied genes (19 genes showed different expressional pattern (up or down-expression based on tumor cell lines. Conclusion: According to the findings of the present study, we may suggest that there is a direct correlation between OCT4B1 expression in tumor cell lines (and tissues and HSP40 family gene expressions to escape from apoptosis and cancer expansion.

  13. B-1 cell immunoglobulin directed against oxidation-specific epitopes

    Directory of Open Access Journals (Sweden)

    Dimitrios eTsiantoulas

    2013-01-01

    Full Text Available Natural antibodies (NAbs are pre-existing antibodies with germline origin that arise in the absence of previous exposure to foreign antigens. NAbs are produced by B-1 lymphocytes and are primarily of the IgM isotype. There is accumulating evidence that - in addition to their role in antimicrobial host defense - NAbs exhibit important housekeeping functions by facilitating the non-immunogenic clearance of apoptotic cells as well as the removal of (neo-self antigens. These properties are largely mediated by the ability of NAbs to recognize highly conserved and endogenously generated structures, which are exemplified by so-called oxidation-specific epitopes (OSEs that are products of lipid peroxidation. The generation of OSEs as well as their interaction with the immune system have been studied extensively in the context of atherosclerosis, a chronic inflammatory disease of the vascular wall that is characterized by the accumulation of cellular debris and oxidized low-density lipoproteins (OxLDL. Both apoptotic cells as well as OxLDL carry OSEs that are targeted by NAbs. Therefore, OSEs represent stress-induced neo-self structures that mediate recognition of metabolic waste (e.g. cellular debris by NAbs, allowing its safe disposal, which has fundamental implications in health and disease.

  14. Solvent-dependent transformation of aflatoxin B1 in soil.

    Science.gov (United States)

    Starr, James M; Rushing, Blake R; Selim, Mustafa I

    2017-08-01

    To date, all studies of aflatoxin B 1 (AFB 1 ) transformation in soil or in purified mineral systems have identified aflatoxins B 2 (AFB 2 ) and G 2 (AFG 2 ) as the primary transformation products. However, identification in these studies was made using thin layer chromatography which has relatively low resolution, and these studies did not identify a viable mechanism by which such transformations would occur. Further, the use of methanol as the solvent delivery vehicle in these studies may have contributed to formation of artifactual transformation products. In this study, we investigated the role of the solvent vehicle in the transformation of AFB 1 in soil. To do this, we spiked soils with AFB 1 dissolved in water (93:7, water/methanol) or methanol and used HPLC-UV and HPLC-MS to identify the transformation products. Contrasting previous published reports, we did not detect AFB 2 or AFG 2 . In an aqueous-soil environment, we identified aflatoxin B 2a (AFB 2a ) as the single major transformation product. We propose that AFB 2a is formed from hydrolysis of AFB 1 with the soil acting as an acid catalyst. Alternatively, when methanol was used, we identified methoxy aflatoxin species likely formed via acid-catalyzed addition of methanol to AFB 1 . These results suggest that where soil moisture is adequate, AFB 1 is hydrolyzed to AFB 2a and that reactive organic solvents should be avoided when replicating natural conditions to study the fate of AFB 1 in soil.

  15. Decomposition and detoxification of aflatoxin B1 by lactic acid.

    Science.gov (United States)

    Aiko, Visenuo; Edamana, Prasad; Mehta, Alka

    2016-04-01

    A degradation study of aflatoxin B1 (AFB1) was carried out using a combination of physical and chemical methods. AFB1 was heated at 80 °C in the presence of acetic, citric and lactic acids for various time periods. The cytotoxicity of the degraded AFB1 and its products were determined by MTT assay. The results showed that among the three organic acids lactic acid was most efficient in degrading AFB1. Although complete degradation was not observed, up to 85% degradation of AFB1 was obtained when heated for 120 min. Degradation of AFB1 was confirmed by the reduced toxicity on HeLa cells using MTT assay. Treatment with lactic acid resulted in the conversion of AFB1 into two degradation products. These products were observed at lower retention factors of 0.63 and 0.38, which were identified as AFB2 and AFB2a, respectively. The cytotoxicity of AFB2a exhibited much reduced toxicity on HeLa cells compared to that of AFB1. The results have shown the efficiency of lactic acid in degrading AFB1. This study suggest that lactic acid may be considered for use in the food and feed industry since it is present naturally in food and is considered safe. © 2015 Society of Chemical Industry.

  16. Amide temperature coefficients in the protein G B1 domain

    International Nuclear Information System (INIS)

    Tomlinson, Jennifer H.; Williamson, Mike P.

    2012-01-01

    Temperature coefficients have been measured for backbone amide 1 H and 15 N nuclei in the B1 domain of protein G (GB1), using temperatures in the range 283–313 K, and pH values from 2.0 to 9.0. Many nuclei display pH-dependent coefficients, which were fitted to one or two pK a values. 1 H coefficients showed the expected behaviour, in that hydrogen-bonded amides have less negative values, but for those amides involved in strong hydrogen bonds in regular secondary structure there is a negative correlation between strength of hydrogen bond and size of temperature coefficient. The best correlation to temperature coefficient is with secondary shift, indicative of a very approximately uniform thermal expansion. The largest pH-dependent changes in coefficient are for amides in loops adjacent to sidechain hydrogen bonds rather than the amides involved directly in hydrogen bonds, indicating that the biggest determinant of the temperature coefficient is temperature-dependent loss of structure, not hydrogen bonding. Amide 15 N coefficients have no clear relationship with structure.

  17. Long-Distance Transport of Thiamine (Vitamin B1) Is Concomitant with That of Polyamines.

    Science.gov (United States)

    Martinis, Jacopo; Gas-Pascual, Elisabet; Szydlowski, Nicolas; Crèvecoeur, Michèle; Gisler, Alexandra; Bürkle, Lukas; Fitzpatrick, Teresa B

    2016-05-01

    Thiamine (vitamin B1) is ubiquitous and essential for cell energy supply in all organisms as a vital metabolic cofactor, known for over a century. In plants, it is established that biosynthesis de novo is taking place predominantly in green tissues and is furthermore limited to plastids. Therefore, transport mechanisms are required to mediate the movement of this polar metabolite from source to sink tissue to activate key enzymes in cellular energy generating pathways but are currently unknown. Similar to thiamine, polyamines are an essential set of charged molecules required for diverse aspects of growth and development, the homeostasis of which necessitates long-distance transport processes that have remained elusive. Here, a yeast-based screen allowed us to identify Arabidopsis (Arabidopsis thaliana) PUT3 as a thiamine transporter. A combination of biochemical, physiological, and genetic approaches permitted us to show that PUT3 mediates phloem transport of both thiamine and polyamines. Loss of function of PUT3 demonstrated that the tissue distribution of these metabolites is altered with growth and developmental consequences. The pivotal role of PUT3 mediated thiamine and polyamine homeostasis in plants, and its importance for plant fitness is revealed through these findings. © 2016 American Society of Plant Biologists. All Rights Reserved.

  18. Predominant porB1A and porB1B genotypes and correlation of gene mutations with drug resistance in Neisseria gonorrhoeae isolates in Eastern China

    Directory of Open Access Journals (Sweden)

    Tang Renxian

    2010-11-01

    Full Text Available Abstract Background Variations of porB1A and porB1B genes and their serotypes exist in Neisseria gonorrhoeae isolates from different geographical areas, and some site mutations in the porB1B gene correlate with drug resistance. Methods The β-lactamase production of N. gonorrhoeae isolates was determined by paper acidometric test and nitrocefin discs. The porB1A and porB1B genes of 315 non-penicillinase-producting N. gonorrhoeae (non-PPNG strains were amplified by PCR for sequencing to determine serotypes and site mutations. A duplex PCR was designed to simultaneously detect both porB1A and porB1B genes. Penicillin and tetracycline resistance was assessed by an in vitro drug sensitivity test. Results Of the N. gonorrhoeae isolates, 31.1% tested positive for porB1A and 68.9% for porB1B genes. All the 98 porB1A+ isolates belonging to IA6 serotype with either no mutation at the 120 and 121 sites (88.8% or a D120G (11.2% mutation and were no resistance to both penicillin and tetracycline. Among the 217 porB1B+ isolates, 26.7%, 22.6% and 11.5% belonged to IB3, IB3/6 and IB4 serotypes, respectively. Particularly, two novel chimeric serotypes, IB3/6-IB2 and IB2-IB4-IB2, were found in 77 and 8 porB1B+ isolates. Two hundred and twelve (97.7% of the porB1B+ isolates were presented G120 and/or A121 mutations with 163 (76.9% at both sites. Interestingly, within the 77 porB1B+ isolates belonging to IB3/6-IB2 serotype, 15 were discovered to possess novel deletions at both A121 and N122 sites. All the replacement mutations at these sites in PorB1B were correlated with resistance and the deletion mutation showed the highest resistance. Conclusion N. gonorrhoeae isolates circulating in Eastern China include a sole PorB1A serotype (IA6 and five PorB1B serotypes. Multiple mutations in porB1B genes, including novel A121 and N122 deletions, are correlated with high levels of penicillin and tetracycline resistance.

  19. Preparation and bioevaluation of 99Tcm-HYNIC-Annexin B1 as a novel radiotracer for apoptosis detection

    International Nuclear Information System (INIS)

    Luo Quanyong; Luo Qiong; Lu Hankui; Zhu Ruisen; Wang Fang; Zhang Yi; Sun Shuhan; Zhang Zhiyong; Liu Xingfeng

    2008-01-01

    Objective: Annexin B1, a novel Ca 2+ -dependent phosphatidylserine (PS)-binding protein, has been shown to have a high affinity for PS exposed on the surface of apoptotic cells or activated platelets. The aim of this study was to develop and bioevaluate an Annexin B1 based PS-targeting radiotracer labeled with 99 Tc m . Methods: Annexin B1 was indirectly labeled with 99 Tc m using hydrazinonicotinamide (HYNIC) as a bifunctional chelator agent. Binding assay with human activated platelets was used to evaluate the biological activity of 99 Tc m -HYNIC-Annexin B1 in vitro. The potential of 99 Tc m -HYNIC-Annexin B1 to detect apoptosis in vivo was evaluated in mice models with dexamethasone-inducecd thymus apoptosis and anti-Fas antibody induced liver apoptosis. The paired t-test was used to analyse the data. Results: The labeling procedure yielded a compound with radiochemical purity higher than 96% and good in vitro stability. Plate- lets binding assay indicated that 99 Tc m -HYNIC-Annexin B1 retained their PS binding activity in vitro. The percentage activity of injection dose per gram of tissue (% ID/g) of mouse thymus showed a 3.50-fold increase at 18 h after administration of dexamethasone compared with control mice (t=5.234, P 99 Tc m -HYNIC-Annexin B1 in the liver of anti-Fas antibody treated mice. The %ID/g of apoptotic murine liver showed a 2.02-fo1d increase at 2 h after the administration of anti-Fas antibody compared with control mice (t=6.178, P 99 Tc m -HYNIC-Annexin B1 can be prepared with high radiochemical purity and in vitro stability. These da- ta also suggest that 99 Tc m -HYNIC-Annexin B1 retains its in vitro and in vivo biological activities. It may therefore be useful as a novel radioligand for the noninvasive imaging of PS externalization associated with apoptosis. (authors)

  20. SLC9B1 methylation predicts fetal intolerance of labor.

    Science.gov (United States)

    Knight, Anna K; Conneely, Karen N; Kilaru, Varun; Cobb, Dawayland; Payne, Jennifer L; Meilman, Samantha; Corwin, Elizabeth J; Kaminsky, Zachary A; Dunlop, Anne L; Smith, Alicia K

    2018-01-01

    Fetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data from 177 unique women who, during their prenatal visits (7-15 weeks and/or 24-32 weeks) to Atlanta area prenatal care clinics, consented to provide blood samples for DNA methylation (HumanMethylation450 BeadChip) and gene expression (Human HT-12 v4 Expression BeadChip) analyses. We focused on 57 women aged 18-36 (mean 25.4), who had DNA methylation data available from their second prenatal visit. DNA methylation patterns at CpG sites across the genome were interrogated for associations with fetal intolerance of labor. Four CpG sites (P value intolerance of labor. DNA methylation and gene expression were negatively associated when examined longitudinally during pregnancy using a linear mixed-effects model. Positive predictive values of methylation of these four sites ranged from 0.80 to 0.89, while negative predictive values ranged from 0.91 to 0.92. The four CpG sites were also associated with fetal intolerance of labor in an independent cohort (the Johns Hopkins Prospective PPD cohort). Therefore, fetal intolerance of labor could be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation. Fetal intolerance of labor may be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation by assessing DNA methylation patterns of SLC9B1. The identification of pregnant women at elevated risk for fetal intolerance of labor may allow for the development of targeted treatments or management plans.

  1. Aflatoxin B1 Degradation by a Pseudomonas Strain

    Directory of Open Access Journals (Sweden)

    Lancine Sangare

    2014-10-01

    Full Text Available Aflatoxin B1 (AFB1, one of the most potent naturally occurring mutagens and carcinogens, causes significant threats to the food industry and animal production. In this study, 25 bacteria isolates were collected from grain kernels and soils displaying AFB1 reduction activity. Based on its degradation effectiveness, isolate N17-1 was selected for further characterization and identified as Pseudomonas aeruginosa. P. aeruginosa N17-1 could degrade AFB1, AFB2 and AFM1 by 82.8%, 46.8% and 31.9% after incubation in Nutrient Broth (NB medium at 37 °C for 72 h, respectively. The culture supernatant of isolate N17-1 degraded AFB1 effectively, whereas the viable cells and intra cell extracts were far less effective. Factors influencing AFB1 degradation by the culture supernatant were investigated. Maximum degradation was observed at 55 °C. Ions Mn2+ and Cu2+ were activators for AFB1 degradation, however, ions Mg2+, Li+, Zn2+, Se2+, Fe3+ were strong inhibitors. Treatments with proteinase K and proteinase K plus SDS significantly reduced the degradation activity of the culture supernatant. No degradation products were observed based on preliminary LC-QTOF/MS analysis, indicating AFB1 was metabolized to degradation products with chemical properties different from that of AFB1. The results indicated that the degradation of AFB1 by P. aeruginosa N17-1 was enzymatic and could have a great potential in industrial applications. This is the first report indicating that the isolate of P. aeruginosa possesses the ability to degrade aflatoxin.

  2. Determination of fumonisin B1 levels in body fluids and hair from piglets fed fumonisin B1-contaminated diets.

    Science.gov (United States)

    Souto, Pollyana C M C; Jager, Alessandra V; Tonin, Fernando G; Petta, Tânia; Di Gregório, Mayra C; Cossalter, Anne-Marie; Pinton, Philippe; Oswald, Isabelle P; Rottinghaus, George E; Oliveira, Carlos A F

    2017-10-01

    The levels of fumonisin B 1 (FB 1 ) residues in plasma, urine, feces and hair from 24 piglets fed FB 1 -contaminated diets containing 3.1, 6.1 or 9.0 μg FB 1 .g -1 for 28 days were determined using liquid chromatography coupled to mass spectrometry (LC-MS/MS). The levels of FB 1 in plasma, urine, feces and pooled hair (n = 3) samples varied from 0.15 to 1.08 μg.L -1 , 16.09-75.01 μg.L -1 , 1.87-13.89 μg.g -1 and 2.08-8.09 ng.g -1 , respectively. Significant correlations (r = 0.808-0.885; P 14 days). The possibility to evaluate hair as a biomarker of fumonisin exposure was established, although further studies are needed to provide physiologically based toxicokinetics of residual FB 1 in the pig hair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. CYP714B1 and CYP714B2 encode gibberellin 13-oxidases that reduce gibberellin activity in rice.

    Science.gov (United States)

    Magome, Hiroshi; Nomura, Takahito; Hanada, Atsushi; Takeda-Kamiya, Noriko; Ohnishi, Toshiyuki; Shinma, Yuko; Katsumata, Takumi; Kawaide, Hiroshi; Kamiya, Yuji; Yamaguchi, Shinjiro

    2013-01-29

    Bioactive gibberellins (GAs) control many aspects of growth and development in plants. GA(1) has been the most frequently found bioactive GA in various tissues of flowering plants, but the enzymes responsible for GA(1) biosynthesis have not been fully elucidated due to the enzymes catalyzing the 13-hydroxylation step not being identified. Because of the lack of mutants defective in this enzyme, biological significance of GA 13-hydroxylation has been unknown. Here, we report that two cytochrome P450 genes, CYP714B1 and CYP714B2, encode GA 13-oxidase in rice. Transgenic Arabidopsis plants that overexpress CYP714B1 or CYP714B2 show semidwarfism. There was a trend that the levels of 13-OH GAs including GA(1) were increased in these transgenic plants. Functional analysis using yeast or insect cells shows that recombinant CYP714B1 and CYP714B2 proteins can convert GA(12) into GA(53) (13-OH GA(12)) in vitro. Moreover, the levels of 13-OH GAs including GA(1) were decreased, whereas those of 13-H GAs including GA(4) (which is more active than GA(1)) were increased, in the rice cyp714b1 cyp714b2 double mutant. These results indicate that CYP714B1 and CYP714B2 play a predominant role in GA 13-hydroxylation in rice. The double mutant plants appear phenotypically normal until heading, but show elongated uppermost internode at the heading stage. Moreover, CYP714B1 and CYP714B2 expression was up-regulated by exogenous application of bioactive GAs. Our results suggest that GA 13-oxidases play a role in fine-tuning plant growth by decreasing GA bioactivity in rice and that they also participate in GA homeostasis.

  4. CYP1B1 gene polymorphisms correlate with an increased risk of urinary bladder cancer in India.

    Science.gov (United States)

    Sankhwar, Monica; Sankhwar, Satya Narayan; Abhishek, Amar; Gupta, Nishi; Rajender, Singh

    2016-04-01

    The urinary bladder is the target of several toxic compounds, which makes the bladder more prone to cancer. Cytochrome P450 1B1 enzyme is present in tumor tissues and metabolizes the polyaromatic carcinogens and activates several procarcinogens that cause DNA damage. We examined the functional single-nucleotide polymorphisms in the CYP1B1 gene to study their association with the urinary bladder cancer. We recruited 234 cases of pure urothelial and 258 bladder cancer-free control samples from the individuals visiting the clinic for various investigations. We genotyped 4 CYP1B1 single-nucleotide polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism analysis. The genotype data were analyzed by the Chi-square test. Haplotypes were constructed to evaluate the joint effect of the 4 polymorphisms. Overall, 3 polymorphisms-rs10012, rs150799650, and rs1056827 (odds ratio [OR] = 2.34, CI: 1.59-3.45, Pbladder cancer. Haplotype analysis suggested GTTC, GTTG, and ATGC to be the risk factors for bladder cancer. Overall, 3 polymorphisms, rs10012, rs1056827, and rs150799650 in the CYP1B1 gene correlate with urinary bladder cancer significantly in the Indo-European population of Uttar Pradesh, India. Further investigations in other populations are advised. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. A positive association between the human tissue kallikerin gene A2233C polymorphism and blood pressure response to benazepril.

    Science.gov (United States)

    Hong, Zhe; Pan, Liying; Fei, Jiali; Ma, Zhangqing; Hong, Zongyuan

    2017-01-01

    It is generally believed that essential hypertension is influenced by both genetic and environmental factors, as well as their interactions. Tissue kallikrein encoded by the tissue kallikrein gene (KLK1) is a key serine proteinase of kallikrein-kinin system, which is capable of generating potent vasactive peptides, kinins, by selective cleavage of the kininogen substrate. It was reported that the A2233 → C polymorphism in KLK1 gene is associated with essential hypertension. The aim of this study was to examine whether the molecular variations of KLK1 play role in determining the therapeutic response to benazepril, an ACE inhibitor. A total of 331 hypertensive individuals were recruited and treated with benazepril for 15 days. A variant impact of KLK1 A2233C was revealed. Chi-square analysis showed that the hypertensive subjects with the mutation genotype (AC + CC) had a higher proportion in systolic blood pressure (SBP, 88.1% vs. 79.0%, χ 2 = 4.141, p = 0.042) and diastolic blood pressure (DBP, 91.1% vs. 79.2%, χ 2 = 9.336, p = 0.002), respectively, to benazepril medication in good responders than in poor responders. Logistic regression analysis indicated that the hypertensive subjects with AC + CC genotype were more sensitive to the benazepril therapy in SBP (OR=1.97, 95% CI: 1.02-3.80, p = 0.044) and DBP (OR = 1.91, 95% CI: 2.69-5.16, p = 0.003), as compared with those hypertensive subjects with AA genotype. Our findings suggest that the A2233C polymorphism of KLK1 may be a marker of evaluation of hypertensive subjects' responses to angiotensin I converting enzyme inhibitors benazepril.

  6. Metabolism of aflatoxin B1 and identification of the major aflatoxin B1-DNA adducts formed in cultured human bronchus and colon

    DEFF Research Database (Denmark)

    Autrup, Herman; Essigmann, John M.; Croy, Robert G.

    1979-01-01

    Aflatoxin B1 and benzo(a)pyrene were activated by both cultured human bronchus and human colon as measured by binding to cellular DNA and protein. The binding of aflatoxin B1 to DNA was dose dependent, and the level of binding was higher in cultured human bronchus than it was in the colon. When c...

  7. Hurricane Satellite (HURSAT) from International Satellite Cloud Climatology Project (ISCCP) B1, Version 6

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Hurricane Satellite (HURSAT) from derived International Satellite Cloud Climatology Project (ISCCP) B1 observations of tropical cyclones worldwide. The B1 data...

  8. Histopathological and Ultrastructural Changes in the Liver and Gills of the Killifish Aphanius Dispar (Cyprinodontidae Exposed to Aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Horiya H. Al-Azri

    2015-06-01

    Full Text Available Aflatoxin B1 (AFB1 is a mycotoxin which can cause serious toxicity to animals and humans.  The aim of this study was to investigate the effects of AFB1 in Aphanius dispar fish and measure residues in tissues after in vivo exposure. Aphanius dispar were fed diets containing 50, 100, 150 and 200 µg AFB1/kg for 10, 20 and 30 days. At the end of the experiment, the liver and gills were dissected out and processed for light and electron microscopy. During the experiment, no external changes or unusual behavior were observed in the fish. Histopathological and ultrastructural changes in liver appeared under all four treatments: 50, 100, 150 and 200 µg AFB1/kg. Gill tissues were affected at high doses of 100,150 and 200 µg AFB1/kg. Accumulation of AFB1 residues in liver and gill tissues was found to be related to a dose and duration of exposure.

  9. 26 CFR 48.4161(b)-1 - Imposition and rates of tax; bows and arrows.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Imposition and rates of tax; bows and arrows. 48.4161(b)-1 Section 48.4161(b)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Sporting Goods § 48.4161(b)-1...

  10. 17 CFR 270.6b-1 - Exemption of employees' securities company pending determination of application.

    Science.gov (United States)

    2010-04-01

    ...' securities company pending determination of application. 270.6b-1 Section 270.6b-1 Commodity and Securities... 1940 § 270.6b-1 Exemption of employees' securities company pending determination of application. Any... Act (54 Stat. 801; 15 U.S.C. 80a-6) shall be exempt, pending final determination of such application...

  11. 17 CFR 240.15b1-1 - Application for registration of brokers or dealers.

    Science.gov (United States)

    2010-04-01

    ... of brokers or dealers. 240.15b1-1 Section 240.15b1-1 Commodity and Securities Exchanges SECURITIES... Rules and Regulations Under the Securities Exchange Act of 1934 Registration of Brokers and Dealers § 240.15b1-1 Application for registration of brokers or dealers. (a) An application for registration of...

  12. Effect of vitamin B1 and mixtures of B1 with other vitamins on cytostatic efficiency of sanazole under irradiation. A study in vitro

    Science.gov (United States)

    Heinrich, Edith; Getoff, Nikola

    2003-06-01

    Experiments in vitro, using bacteria Escherichia coli (AB 1157) as a biological model, showed that the cytostatic efficiency of sanazole (AK-2123, a nitrotriazole-type radiosensitizer) in radiation treatment can be strongly influenced by the presence of various vitamins. In airfree media the sanazole action is increased by a factor of 2.5 in the presence of vitamin (vit.) B1, vit. C E-acetate and β-carotene, whereas vit. B1 used individually possesses a 2.7-times higher cytostatic activity than sanazole itself. In media containing air the highest increase of sanazole action is observed in the presence of vit. B1 and C, whereas the individual use of vit. B1 shows a radiation protection effect. In media saturated with N 2O the addition of the vit. B1 and C causes a 1.8-times larger sanazole activity, but the application of vit. B1 alone brings about a very high radiation protection. From studies of vit. B1-radiolysis it can be concluded that OH radicals are the major primary transients leading to substrate degradation. The results are of interest for the radiation therapy of cancer.

  13. Effect of vitamin B1 and mixtures of B1 with other vitamins on cytostatic efficiency of sanazole under irradiation. A study in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Heinrich, Edith; Getoff, Nikola E-mail: nikola.getoff@univie.ac.at

    2003-06-01

    Experiments in vitro, using bacteria Escherichia coli (AB 1157) as a biological model, showed that the cytostatic efficiency of sanazole (AK-2123, a nitrotriazole-type radiosensitizer) in radiation treatment can be strongly influenced by the presence of various vitamins. In airfree media the sanazole action is increased by a factor of 2.5 in the presence of vitamin (vit.) B1, vit. C E-acetate and {beta}-carotene, whereas vit. B1 used individually possesses a 2.7-times higher cytostatic activity than sanazole itself. In media containing air the highest increase of sanazole action is observed in the presence of vit. B1 and C, whereas the individual use of vit. B1 shows a radiation protection effect. In media saturated with N{sub 2}O the addition of the vit. B1 and C causes a 1.8-times larger sanazole activity, but the application of vit. B1 alone brings about a very high radiation protection. >From studies of vit. B1-radiolysis it can be concluded that OH radicals are the major primary transients leading to substrate degradation. The results are of interest for the radiation therapy of cancer.

  14. Effect of vitamin B1 and mixtures of B1 with other vitamins on cytostatic efficiency of sanazole under irradiation. A study in vitro

    International Nuclear Information System (INIS)

    Heinrich, Edith; Getoff, Nikola

    2003-01-01

    Experiments in vitro, using bacteria Escherichia coli (AB 1157) as a biological model, showed that the cytostatic efficiency of sanazole (AK-2123, a nitrotriazole-type radiosensitizer) in radiation treatment can be strongly influenced by the presence of various vitamins. In airfree media the sanazole action is increased by a factor of 2.5 in the presence of vitamin (vit.) B1, vit. C E-acetate and β-carotene, whereas vit. B1 used individually possesses a 2.7-times higher cytostatic activity than sanazole itself. In media containing air the highest increase of sanazole action is observed in the presence of vit. B1 and C, whereas the individual use of vit. B1 shows a radiation protection effect. In media saturated with N 2 O the addition of the vit. B1 and C causes a 1.8-times larger sanazole activity, but the application of vit. B1 alone brings about a very high radiation protection. >From studies of vit. B1-radiolysis it can be concluded that OH radicals are the major primary transients leading to substrate degradation. The results are of interest for the radiation therapy of cancer

  15. Sulfolobus Replication Factor C stimulates the activity of DNA Polymerase B1

    DEFF Research Database (Denmark)

    Xing, Xuanxuan; Zhang, Likui; Guo, Li

    2014-01-01

    the hyperthermophilic archaea of the genus Sulfolobus physically interacts with DNA polymerase B1 (PolB1) and enhances both the polymerase and 3'-5' exonuclease activities of PolB1 in an ATP-independent manner. Stimulation of the PolB1 activity by RFC is independent of the ability of RFC to bind DNA but is consistent...... with the ability of RFC to facilitate DNA binding by PolB1 through protein-protein interaction. These results suggest that Sulfolobus RFC may play a role in recruiting DNA polymerase for efficient primer extension, in addition to clamp loading, during DNA replication....

  16. Microvesicle transfer of kinin B1-receptors is a novel inflammatory mechanism in vasculitis.

    Science.gov (United States)

    Kahn, Robin; Mossberg, Maria; Ståhl, Anne-Lie; Johansson, Karl; Lopatko Lindman, Ingrid; Heijl, Caroline; Segelmark, Mårten; Mörgelin, Matthias; Leeb-Lundberg, L M Fredrik; Karpman, Diana

    2017-01-01

    During vasculitis, activation of the kinin system induces inflammation, whereby the kinin B1-receptor is expressed and activated after ligand binding. Additionally, activated blood cells release microvesicles into the circulation. Here we determined whether leukocyte-derived microvesicles bear B1-kinin receptors during vasculitis, and if microvesicles transfer functional B1-receptors to recipient cells, thus promoting inflammation. By flow cytometry, plasma from patients with vasculitis were found to contain high levels of leukocyte-derived microvesicles bearing B1-receptors. Importantly, renal biopsies from two patients with vasculitis showed leukocyte-derived microvesicles bearing B1-receptors docking on glomerular endothelial cells providing in vivo relevance. Microvesicles derived from B1-receptor-transfected human embryonic kidney cells transferred B1-receptors to wild-type human embryonic kidney cells, lacking the receptor, and to glomerular endothelial cells. The transferred B1-receptors induced calcium influx after B1-receptor agonist stimulation: a response abrogated by a specific B1-receptor antagonist. Microvesicles derived from neutrophils also transferred B1-receptors to wild-type human embryonic kidney cells and induced calcium influx after stimulation. Thus, we found a novel mechanism by which microvesicles transfer functional receptors and promote kinin-associated inflammation. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  17. Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1.

    Science.gov (United States)

    Meyer Zu Schwabedissen, Henriette E; Ferreira, Celio; Schaefer, Anima M; Oufir, Mouhssin; Seibert, Isabell; Hamburger, Matthias; Tirona, Rommel G

    2018-07-01

    Levothyroxine replacement therapy forms the cornerstone of hypothyroidism management. Variability in levothyroxine oral absorption may contribute to the well-recognized large interpatient differences in required dose. Moreover, levothyroxine-drug pharmacokinetic interactions are thought to be caused by altered oral bioavailability. Interestingly, little is known regarding the mechanisms contributing to levothyroxine absorption in the gastrointestinal tract. Here, we aimed to determine whether the intestinal drug uptake transporter organic anion transporting polypeptide 2B1 (OATP2B1) may be involved in facilitating intestinal absorption of thyroid hormones. We also explored whether thyroid hormones regulate OATP2B1 gene expression. In cultured Madin-Darby Canine Kidney II/OATP2B1 cells and in OATP2B1-transfected Caco-2 cells, thyroid hormones were found to inhibit OATP2B1-mediated uptake of estrone-3-sulfate. Competitive counter-flow experiments evaluating the influence on the cellular accumulation of estrone-3-sulfate in the steady state indicated that thyroid hormones were substrates of OATP2B1. Additional evidence that thyroid hormones were OATP2B1 substrates was provided by OATP2B1-dependent stimulation of thyroid hormone receptor activation in cell-based reporter assays. Bidirectional transport studies in intestinal Caco-2 cells showed net absorptive flux of thyroid hormones, which was attenuated by the presence of the OATP2B1 inhibitor, atorvastatin. In intestinal Caco-2 and LS180 cells, but not in liver Huh-7 or HepG2 cells, OATP2B1 expression was induced by treatment with thyroid hormones. Reporter gene assays revealed thyroid hormone receptor α -mediated transactivation of the SLCO2B1 1b and the SLCO2B1 1e promoters. We conclude that thyroid hormones are substrates and transcriptional regulators of OATP2B1. These insights provide a potential mechanistic basis for oral levothyroxine dose variability and drug interactions. Copyright © 2018 by The American

  18. Observations and light curve solutions of the eclipsing binaries USNO-B1.0 1395-0370184 and USNO-B1.0 1395-0370731

    Directory of Open Access Journals (Sweden)

    Kjurkchieva D.

    2016-01-01

    Full Text Available We present follow-up photometric observations in Sloan filters g', i' of the newly discovered eclipsing stars USNO-B1.0 1395-0370184 and USNO-B1.0 1395-0370731. Our data revealed that their orbital periods are considerably bigger than the previous values. This result changed the classification of USNO-B1.0 1395-0370184 from ultrashort-period binary (P=0.197 d to short-period system (P=0.251 d. The light curve solutions of our observations revealed that USNOB1.0 1395-0370184 and USNO-B1.0 1395-0370731 are overcontact binaries in which components are K dwarfs, close in masses and radii. The light curve distortions were reproduced by cool spots with angular radius of around 20°.

  19. NOAA Climate Data Record (CDR) of Gridded Satellite Data from ISCCP B1 (GridSat-B1) Infrared Channel Brightness Temperature, Version 2

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Gridded Satellite (GridSat-B1) data provides a uniform set of quality controlled geostationary satellite observations for the visible, infrared window and...

  20. Cell stress promotes the association of phosphorylated HspB1 with F-actin.

    Directory of Open Access Journals (Sweden)

    Joseph P Clarke

    Full Text Available Previous studies have suggested that the small heat shock protein, HspB1, has a direct influence on the dynamics of cytoskeletal elements, in particular, filamentous actin (F-actin polymerization. In this study we have assessed the influence of HspB1 phosphorylation on its interaction(s with F-actin. We first determined the distribution of endogenous non-phosphorylated HspB1, phosphorylated HspB1 and F-actin in neuroendocrine PC12 cells by immunocytochemistry and confocal microscopy. We then investigated a potential direct interaction between HspB1 with F-actin by precipitating F-actin directly with biotinylated phalloidin followed by Western analyses; the reverse immunoprecipitation of HspB1 was also carried out. The phosphorylation influence of HspB1 in this interaction was investigated by using pharmacologic inhibition of p38 MAPK. In control cells, HspB1 interacts with F-actin as a predominantly non-phosphorylated protein, but subsequent to stress there is a redistribution of HspB1 to the cytoskeletal fraction and a significantly increased association of pHspB1 with F-actin. Our data demonstrate HspB1 is found in a complex with F-actin both in phosphorylated and non-phosphorylated forms, with an increased association of pHspB1 with F-actin after heat stress. Overall, our study combines both cellular and biochemical approaches to show cellular localization and direct demonstration of an interaction between endogenous HspB1 and F-actin using methodolgy that specifically isolates F-actin.

  1. Phytic acid decreases deoxynivalenol and fumonisin B1-induced changes on swine jejunal explants

    Directory of Open Access Journals (Sweden)

    Elisângela Olegário da Silva

    2014-01-01

    Full Text Available The purpose of the present study was to investigate the effects of phytic acid (IP6 on morphological and immunohistochemical parameters on intestinal explants exposed to deoxynivalenol (DON and fumonisin B1 (FB1. The jejunal explants were exposed for 4 h to different treatments: control, DON (10 μM, DON plus 2.5 mM or 5 mM IP6, FB1 (70 μM, and FB1 plus 2.5 mM or 5 mM IP6. Both mycotoxins induced significant intestinal lesions and decreased villi height. The presence of 2.5 mM and 5 mM IP6 significantly inhibited the morphological changes caused by the mycotoxins. DON induced a significant increase in caspase-3 (83% and cyclooxygenase-2 (71.3% expression compared with the control. The presence of 5 mM IP6 induced a significant decrease in caspase-3 (43.7% and Cox-2 (48% expression compared with the DON group. FB1 induced a significant increase in caspase-3 expression (47% compared to the control, whereas IP6 induced no significant change in this expression. A significant decrease in cell proliferation was observed when explants were exposed to 5 mM of IP6 in comparison with the DON and FB1 groups. The present data provide evidence that phytic acid modulates the toxic effects induced by DON and FB1 on intestinal tissue.

  2. Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B1

    International Nuclear Information System (INIS)

    Westhuizen, Liana van der; Gelderblom, Wentzel C.A.; Shephard, Gordon S.; Swanevelder, Sonja

    2004-01-01

    In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B 1 (FB 1 ) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB 1 containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB 1 dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB 1 treatment in the control rats was significantly (P 1 initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB 1 treatment, the initiation effected by FB 1 was less (P 1 initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P 1 treatment. Although, the FB 1 -induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P)

  3. Hepatic Transcriptome Responses of Domesticated and Wild Turkey Embryos to Aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Melissa S. Monson

    2016-01-01

    Full Text Available The mycotoxin, aflatoxin B1 (AFB1 is a hepatotoxic, immunotoxic, and mutagenic contaminant of food and animal feeds. In poultry, AFB1 can be maternally transferred to embryonated eggs, affecting development, viability and performance after hatch. Domesticated turkeys (Meleagris gallopavo are especially sensitive to aflatoxicosis, while Eastern wild turkeys (M. g. silvestris are likely more resistant. In ovo exposure provided a controlled AFB1 challenge and comparison of domesticated and wild turkeys. Gene expression responses to AFB1 in the embryonic hepatic transcriptome were examined using RNA-sequencing (RNA-seq. Eggs were injected with AFB1 (1 μg or sham control and dissected for liver tissue after 1 day or 5 days of exposure. Libraries from domesticated turkey (n = 24 and wild turkey (n = 15 produced 89.2 Gb of sequence. Approximately 670 M reads were mapped to a turkey gene set. Differential expression analysis identified 1535 significant genes with |log2 fold change| ≥ 1.0 in at least one pair-wise comparison. AFB1 effects were dependent on exposure time and turkey type, occurred more rapidly in domesticated turkeys, and led to notable up-regulation in cell cycle regulators, NRF2-mediated response genes and coagulation factors. Further investigation of NRF2-response genes may identify targets to improve poultry resistance.

  4. A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells.

    Science.gov (United States)

    Hadland, Brandon K; Varnum-Finney, Barbara; Mandal, Pankaj K; Rossi, Derrick J; Poulos, Michael G; Butler, Jason M; Rafii, Shahin; Yoder, Mervin C; Yoshimoto, Momoko; Bernstein, Irwin D

    2017-06-06

    Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs). However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC) potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Brandon K. Hadland

    2017-06-01

    Full Text Available Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs. However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes.

  6. Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Li-Chuan; Li, Lih-Ann, E-mail: lihann@nhri.org.tw

    2012-02-01

    CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

  7. Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

    International Nuclear Information System (INIS)

    Cheng, Li-Chuan; Li, Lih-Ann

    2012-01-01

    CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. The Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased CYP11B1

  8. Nongenomic effects of 1α,25-dihydroxyvitamin D3 on cartilage formation deduced from comparisons between Cyp27b1 and Vdr knockout mice

    International Nuclear Information System (INIS)

    Hirota, Yoshihisa; Nakagawa, Kimie; Mimatsu, Shino; Sawada, Natsumi; Sakaki, Toshiyuki; Kubodera, Noboru; Kamao, Maya; Tsugawa, Naoko; Suhara, Yoshitomo; Okano, Toshio

    2017-01-01

    The active form of vitamin D, 1α,25-dihydroxyvitamin D 3 (1α,25D 3 ), plays an important role in the maintenance of calcium (Ca) homeostasis, bone formation, and cell proliferation and differentiation via nuclear vitamin D receptor (VDR). It is formed by the hydroxylation of vitamin D at the 1α position by 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) in the kidney. However, Cyp27b1 −/− mice, deficient in CYP27B1, and VDR-deficient mice (Vdr −/− ) have not been extensively examined, particularly in a comparative framework. To clarify the physiological significance of 1α,25D 3 and VDR, we produced Cyp27b1 −/− mice and compared their phenotypes with those of Vdr −/− mice. Cyp27b1 −/− mice exhibited hypocalcemia, growth defects, and skeletogenesis dysfunction, similar to Vdr −/− mice. However, unlike Cyp27b1 −/− mice, Vdr −/− mice developed alopecia. Cyp27b1 −/− mice exhibited cartilage mass formation and had difficulty walking on hindlimbs. Furthermore, a phenotypic analysis was performed on Cyp27b1 −/− mice provided a high Ca diet to correct for the Ca metabolic abnormality. In addition, the effects of 1α,25D 3 that are not mediated by Ca metabolic regulatory activity were investigated. Even when the blood Ca concentration was corrected, abnormalities in growth and cartilage tissue formation did not improve in Cyp27b1 −/− mice. These results suggested that 1α,25D 3 directly controls chondrocyte proliferation and differentiation. Using Cyp27b1 −/− mice produced in this study, we can analyze the physiological effects of novel vitamin D derivatives in the absence of endogenous 1α,25D 3 . Accordingly, this study provides a useful animal model for the development of novel vitamin D formulations that are effective for the treatment and prevention of osteoporosis. - Highlights: • We produced Cyp27b1 −/− mice and analyzed their phenotypes. • Vdr −/− mice exhibited alopecia and Cyp27b1 −/− mice exhibited

  9. Highly sensitive FRET-based fluorescence immunoassay for aflatoxin B1 using cadmium telluride quantum dots

    International Nuclear Information System (INIS)

    Zekavati, Roya; Bayat, Mansour; Safi, Shahabeddin; Hashemi, Seyed Jamal; Rahmani-Cherati, Tavoos; Tabatabaei, Meisam; Mohsenifar, Afshin

    2013-01-01

    We report on a competitive immunoassay for the determination of aflatoxin B1 using fluorescence resonance energy transfer (FRET) from anti-aflatoxin B1 antibody (immobilized on the shell of CdTe quantum dots) to Rhodamine 123 (Rho 123-labeled aflatoxin B1 bound to albumin). The highly specific immuno reaction between the antibody against aflatoxin B1 on the QDs and the labeled-aflatoxin B1 brings the Rho 123 fluorophore (acting as the acceptor) and the QDs (acting as the donor) in close spatial proximity and causes FRET to occur upon photoexcitation of the QDs. In the absence of unlabeled aflatoxin B1, the antigen-antibody complex is stable, and strong emission resulting from the FRET from QDs to labeled aflatoxin B1 is observed. In the presence of aflatoxin B1, it will compete with the labeled aflatoxin B1-albumin complex for binding to the antibody-QDs conjugate so that FRET will be increasingly suppressed. The reduction in the fluorescence intensity of the acceptor correlates well with the concentration of aflatoxin B1. The feasibility of the method was established by the detection of aflatoxin B1 in spiked human serum. There is a linear relationship between the increased fluorescence intensity of Rho 123 with increasing concentration of aflatoxin B1 in spike human serum, over the range of 0.1–0.6 μmol·mL −1 . The limit of detection is 2 × 10 −11 M. This homogeneous competitive detection scheme is simple, rapid and efficient, and does not require excessive washing and separation steps. (author)

  10. In vitro studies on chemoprotective effect of borax against aflatoxin B1-induced genetic damage in human lymphocytes.

    Science.gov (United States)

    Turkez, Hasan; Geyikoğlu, Fatime; Dirican, Ebubekir; Tatar, Abdulgani

    2012-12-01

    A common dietary contaminant, aflatoxin B1 (AFB1), has been shown to be a potent mutagen and carcinogen in humans and many animal species. Since the eradication of AFB1 contamination in agricultural products has been rare, the use of natural or synthetic free radical scavengers could be a potential chemopreventive strategy. Boron compounds like borax (BX) and boric acid are the major components of industry and their antioxidant role has recently been reported. In the present report, we evaluated the capability of BX to inhibit the rate of micronucleus (MN) and sister chromatid exchange (SCE) formations induced by AFB1. There were significant increases (P Borax gave 30-50 % protection against AFB1 induced SCEs and MNs. In conclusion, the support of borax was especially useful in aflatoxin-toxicated blood tissue. Thus, the risk on target tissues of AFB1 could be reduced and ensured early recovery from its toxicity.

  11. Selective boron accumulation in human ocular melanoma by 10B1-para-boronophenylalanine administration for neutron capture therapy

    International Nuclear Information System (INIS)

    Wadabayashi, Nobutoshi; Ichihashi, Masamitsu; Honda, Chihiro; Mishima, Yutaka.

    1994-01-01

    Malignant melanoma occurs not only in the skin but also in ocular tissues. Ocular melanoma located superficially as in conjunctiva can be treated successfully by BNCT. In the present study, we investigated 10 B dynamics in ocular melanoma and the surrounding normal tissues, to evaluate the possibility of applying BNCT to ocular melanoma. In three ocular melanoma patients, 10 B concentration in melanoma after administration of 10 B-BPA by oral or drip infusion ranged from 10.4 to 21.5 ppm. The boron concentrations in lens and vitreous body were lower than blood level, whereas higher than blood in sclera and palpebral skin. These results suggest that we can treat such a superficial melanoma lesions as conjunctival melanoma by BNCT using 10 B 1 -BPA. (author)

  12. Lactobacillus plantarum MYS6 Ameliorates Fumonisin B1-Induced Hepatorenal Damage in Broilers

    Directory of Open Access Journals (Sweden)

    B. V. Deepthi

    2017-11-01

    Full Text Available Fumonisin B1 (FB1, a mycotoxin produced by Fusarium species is a predominant Group 2B carcinogen occurring in maize and maize-based poultry feeds. It is shown to be nephrotoxic, hepatotoxic, neurotoxic, and immunosuppressing in animals. In this study, we report the ameliorating effects of a probiotic strain, Lactobacillus plantarum MYS6 on FB1-induced toxicity and oxidative damage in broilers. A 6-week dietary experiment consisting of 48 broilers was performed in six treatment groups. Probiotic treatment (109 cells/mL involved pre-colonization of broilers with L. plantarum MYS6 while co-administration treatment involved supplementation of probiotic and FB1-contaminated diet (200 mg/Kg feed simultaneously. At the end of the treatment period, growth performance, hematology, serum biochemistry, and markers of oxidative stress in serum and tissue homogenates were evaluated in all the broilers. The histopathological changes in hepatic and renal tissues were further studied. The results demonstrated that administration of L. plantarum MYS6 efficiently improved the feed intake, body weight and feed conversion ratio in broilers. It mitigated the altered levels of hematological indices such as complete blood count, hemoglobin, and hematocrit. Serum parameters such as serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, creatinine, cholesterol, triglycerides, and albumin were significantly restored after administering the probiotic in FB1-intoxicated broilers. Additionally, L. plantarum MYS6 alleviated the levels of oxidative stress markers in serum and tissue homogenate of liver. The histopathological data of liver and kidney further substantiated the overall protection offered by L. plantarum MYS6 against FB1-induced cellular toxicity and organ damage in broilers. Our results indicated that co-administration of probiotic along with the toxin had better effect in detoxification compared to its pre-colonization in broilers

  13. A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A.

    LENUS (Irish Health Repository)

    Mullan, Ronan Hugh

    2012-02-01

    Acute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G-coupled receptor FPRL-1. Here we report alternative signaling through the high-density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression\\/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology\\/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial\\/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and -8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA.

  14. A Highly Sensitive Porous Silicon (P-Si)-Based Human Kallikrein 2 (hK2) Immunoassay Platform toward Accurate Diagnosis of Prostate Cancer.

    Science.gov (United States)

    Lee, Sang Wook; Hosokawa, Kazuo; Kim, Soyoun; Jeong, Ok Chan; Lilja, Hans; Laurell, Thomas; Maeda, Mizuo

    2015-05-22

    Levels of total human kallikrein 2 (hK2), a protein involved the pathology of prostate cancer (PCa), could be used as a biomarker to aid in the diagnosis of this disease. In this study, we report on a porous silicon antibody immunoassay platform for the detection of serum levels of total hK2. The surface of porous silicon has a 3-dimensional macro- and nanoporous structure, which offers a large binding capacity for capturing probe molecules. The tailored pore size of the porous silicon also allows efficient immobilization of antibodies by surface adsorption, and does not require chemical immobilization. Monoclonal hK2 capture antibody (6B7) was dispensed onto P-Si chip using a piezoelectric dispenser. In total 13 × 13 arrays (169 spots) were spotted on the chip with its single spot volume of 300 pL. For an optimization of capture antibody condition, we firstly performed an immunoassay of the P-Si microarray under a titration series of hK2 in pure buffer (PBS) at three different antibody densities (75, 100 and 145 µg/mL). The best performance of the microarray platform was seen at 100 µg/mL of the capture antibody concentration (LOD was 100 fg/mL). The platform then was subsequently evaluated for a titration series of serum-spiked hK2 samples. The developed platform utilizes only 15 µL of serum per test and the total assay time is about 3 h, including immobilization of the capture antibody. The detection limit of the hK2 assay was 100 fg/mL in PBS buffer and 1 pg/mL in serum with a dynamic range of 106 (10(-4) to 10(2) ng/mL).

  15. Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

    Directory of Open Access Journals (Sweden)

    Strebhardt Klaus

    2008-12-01

    Full Text Available Abstract Background Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1, is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. Methods In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Results Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Conclusion Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.

  16. Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

    International Nuclear Information System (INIS)

    Androic, Ilija; Krämer, Andrea; Yan, Ruilan; Rödel, Franz; Gätje, Regine; Kaufmann, Manfred; Strebhardt, Klaus; Yuan, Juping

    2008-01-01

    Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA) on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy

  17. UNC93B1 mediates host resistance to infection with Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Mariane B Melo

    2010-08-01

    Full Text Available UNC93B1 associates with Toll-Like Receptor (TLR 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient '3d' mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFα and IFNγ, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wild-type and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNγ by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in non-activated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNγ production as well as autonomous control of Toxoplasma replication by macrophages.

  18. 26 CFR 1.6050B-1 - Information returns by person making unemployment compensation payments.

    Science.gov (United States)

    2010-04-01

    ... unemployment compensation payments. 1.6050B-1 Section 1.6050B-1 Internal Revenue INTERNAL REVENUE SERVICE... Information returns by person making unemployment compensation payments. For taxable years beginning after December 31, 1978, every person who makes payments of unemployment compensation (as defined in section 85...

  19. 26 CFR 1.802(b)-1 - Tax on life insurance companies.

    Science.gov (United States)

    2010-04-01

    .... For the definition of the term “1954 life insurance company taxable income”, see § 1.805-1. (b) The... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Tax on life insurance companies. 1.802(b)-1...) INCOME TAX (CONTINUED) INCOME TAXES Life Insurance Companies § 1.802(b)-1 Tax on life insurance companies...

  20. Immunosuppressive effects of fumonisin B1 in the Trichinella spiralis model

    NARCIS (Netherlands)

    Nijs M de; Egmond HP van; Jong WH de; Loveren H van; LPI; ARO; MGB

    Fumonisin B1 is a mycotoxin produced by Fusarium moniliforme and is found mainly in maize. Fumonisin B1 has been associated with human esophageal cancer, lung edema in pigs and leuko-encephalomalacia in equine species. Adverse effects of this mycotoxin on the immune system can be expected but were

  1. Preparation and application of new fluorescein-labeled fumonisins B1 in fluorescence polarization analysis technique

    Science.gov (United States)

    Objective: To prepare a new fluorescent tracer against common mycotoxins such as fumonisin B1 in order to replace 6-(4,6-Dichlorotriazinyl) aminofluorescein (6-DTAF), an expensive marker, and to develop a technique for quick detection of fumonisin B1 based on the principle of fluorescence polarizati...

  2. Wt-ko_trxB1_Filtered bkg correc transf-norm

    OpenAIRE

    Serrano, L.M.; Molenaar, Douwe; Teusink, Bas; Vos, de, Willem; Smid, Eddy

    2007-01-01

    In this experiment we analyzed the impact of the disruption of trxB1in Lactobacillus plantarum at the transcriptome level. Furthermore we studied the effect of 3.5 mM peroxide effect on both Lactobacillus plantarum wild type (strain WCFS1) and a trxB1 mutant (strain NZ7608).

  3. Production of milk-clotting enzyme by Bacillus subtilis B1 from wheat ...

    African Journals Online (AJOL)

    Three strains, Bacillus subtilis B1, B. subtilis B18 and Bacillus thuringiensis B12, were screened from wheat bran to produce milk-clotting enzyme. Among them, B. subtilis B1 exhibited considerable milkclotting activity with low proteolytic activity. After response surface methodology optimization, milkclotting activity was ...

  4. The use of MR B+1 imaging for validation of FDTD electromagnetic simulations of human anatomies

    International Nuclear Information System (INIS)

    Berg, Cornelis A T van den; Bartels, Lambertus W; Bergen, Bob van den; Kroeze, Hugo; Leeuw, Astrid A C de; Kamer, Jeroen B van de; Lagendijk, Jan J W

    2006-01-01

    In this study, MR B + 1 imaging is employed to experimentally verify the validity of FDTD simulations of electromagnetic field patterns in human anatomies. Measurements and FDTD simulations of the B + 1 field induced by a 3 T MR body coil in a human corpse were performed. It was found that MR B + 1 imaging is a sensitive method to measure the radiofrequency (RF) magnetic field inside a human anatomy with a precision of approximately 3.5%. A good correlation was found between the B + 1 measurements and FDTD simulations. The measured B + 1 pattern for a human pelvis consisted of a global, diagonal modulation pattern plus local B + 1 heterogeneties. It is believed that these local B + 1 field variations are the result of peaks in the induced electric currents, which could not be resolved by the FDTD simulations on a 5 mm 3 simulation grid. The findings from this study demonstrate that B + 1 imaging is a valuable experimental technique to gain more knowledge about the dielectric interaction of RF fields with the human anatomy

  5. Data of evolutionary structure change: 1JJ4B-1R8HE [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available in>B 1JJ4B RLRKH-SDHYR >HGGGG-GGG ...n> RLNDKHRHLFD ture>HHHHH GGG .../pdbID> B 1JJ4B WHWTE-----KTGIL ...> ----- EEE> ATOM 1523 CA TRP B 320 11.497 15.32...1R8HE WHWASPKAPHKHAIV > EEE>

  6. A lattice QCD calculation of the transverse decay constant of the b1(1235) meson

    International Nuclear Information System (INIS)

    Jansen, K.; McNeile, C.; Michael, C.; Urbach, C.

    2009-10-01

    We review various B meson decays that require knowledge of the transverse decay constant of the b 1 (1235) meson. We report on an exploratory lattice QCD calculation of the transverse decay constant of the b 1 meson. The lattice QCD calculations used unquenched gauge configurations, at two lattice spacings, generated with two flavours of sea quarks. The twisted mass formalism is used. (orig.)

  7. Intestinal bile salt absorption in Atp8b1 deficient mice

    NARCIS (Netherlands)

    Groen, Annemiek; Kunne, Cindy; Paulusma, Coen C.; Kramer, Werner; Agellon, Luis B.; Bull, Laura N.; Elferink, Ronald P. J. Oude

    2007-01-01

    BACKGROUND/AIMS: Mutations in the ATP8B1 gene can cause Progressive Familial Intrahepatic Cholestasis type 1. We have previously reported that Atp8b1(G308V/G308V) mice, a model for PFIC1, have slightly, but significantly, higher baseline serum bile salt (BS) concentrations compared to wt mice. Upon

  8. Identification of Ppd-B1 alleles in common wheat cultivars by CAPS marker.

    Science.gov (United States)

    Okoń, S; Kowalczyk, K; Miazga, D

    2012-05-01

    Photoperiod response is a major determinant of the duration of growth stages in common wheat. In common wheat, many genes play a role in determining flowering time, but the Ppd genes located on the homoeologous group 2 play a major role. Of these Ppd-B1 is located on the short arm of 2B. In 107 common wheat cultivars grown in Poland and neighboring countries, the identification of Ppd-B1 alleles using in-del analysis by using a CAPS markers was investigated. 87 cultivars were shown to carry dominant Ppd-B1 alleles. This shows that Ppd-B1 alleles is have been widely used in common wheat breeding programme in these countries. Recessive ppd-B1 alleles were found only in 20 cultivars (12 Polish, 5 former Soviet Union, 2 German, 1 Swedish).

  9. Revaluasi Inventory dengan Menu Standard pada SAP-B1 Sesuaikah dengan IFRS

    Directory of Open Access Journals (Sweden)

    Eka Novianti

    2011-05-01

    Full Text Available Some available standard modules in SAP-B1 can be adapted for changes in accounting rules and regulations. One is the Inventory Revaluation menu of Inventory module. Users can use the menu to make Inventory value adjustments of value in SAP-B1, to be consistent with the values that must be presented in the financial statements. Based on the flexibility provided by SAP-B1menu, should not be too difficult for users of SAP-B1 to manage accounting transactions based on accounting rules that apply today, IFRS. IFRS requirements on inventory adjustment transactions with a value of SAP-B1 could be done more easily.

  10. Key role for spinal dorsal horn microglial kinin B1 receptor in early diabetic pain neuropathy

    Directory of Open Access Journals (Sweden)

    Couture Réjean

    2010-06-01

    Full Text Available Abstract Background The pro-nociceptive kinin B1 receptor (B1R is upregulated on sensory C-fibres, astrocytes and microglia in the spinal cord of streptozotocin (STZ-diabetic rat. This study aims at defining the role of microglial kinin B1R in diabetic pain neuropathy. Methods Sprague-Dawley rats were made diabetic with STZ (65 mg/kg, i.p., and 4 days later, two specific inhibitors of microglial cells (fluorocitrate, 1 nmol, i.t.; minocycline, 10 mg/kg, i.p. were administered to assess the impact on thermal hyperalgesia, allodynia and mRNA expression (qRT-PCR of B1R and pro-inflammatory markers. Spinal B1R binding sites ((125I-HPP-desArg10-Hoe 140 were also measured by quantitative autoradiography. Inhibition of microglia was confirmed by confocal microscopy with the specific marker Iba-1. Effects of intrathecal and/or systemic administration of B1R agonist (des-Arg9-BK and antagonists (SSR240612 and R-715 were measured on neuropathic pain manifestations. Results STZ-diabetic rats displayed significant tactile and cold allodynia compared with control rats. Intrathecal or peripheral blockade of B1R or inhibition of microglia reversed time-dependently tactile and cold allodynia in diabetic rats without affecting basal values in control rats. Microglia inhibition also abolished thermal hyperalgesia and the enhanced allodynia induced by intrathecal des-Arg9-BK without affecting hyperglycemia in STZ rats. The enhanced mRNA expression (B1R, IL-1β, TNF-α, TRPV1 and Iba-1 immunoreactivity in the STZ spinal cord were normalized by fluorocitrate or minocycline, yet B1R binding sites were reduced by 38%. Conclusion The upregulation of kinin B1R in spinal dorsal horn microglia by pro-inflammatory cytokines is proposed as a crucial mechanism in early pain neuropathy in STZ-diabetic rats.

  11. SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells.

    Science.gov (United States)

    Mortera-Blanco, Teresa; Dimitriou, Marios; Woll, Petter S; Karimi, Mohsen; Elvarsdottir, Edda; Conte, Simona; Tobiasson, Magnus; Jansson, Monika; Douagi, Iyadh; Moarii, Matahi; Saft, Leonie; Papaemmanuil, Elli; Jacobsen, Sten Eirik W; Hellström-Lindberg, Eva

    2017-08-17

    Mutations in the RNA splicing gene SF3B1 are found in >80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients and were also present in downstream myeloid and erythroid progenitor cells. While in agreement with previous studies, little or no evidence for clonal ( SF3B1 mutation) involvement could be found in mature B cells, consistent involvement at the pro-B-cell progenitor stage was established, providing definitive evidence for SF3B1 mutations targeting lymphomyeloid HSCs and compatible with mutated SF3B1 negatively affecting lymphoid development. Assessment of stem cell function in vitro as well as in vivo established that only HSCs and not investigated progenitor populations could propagate the SF3B1 mutated clone. Upon transplantation into immune-deficient mice, SF3B1 mutated MDS-RS HSCs differentiated into characteristic ring sideroblasts, the hallmark of MDS-RS. Our findings provide evidence of a multipotent lymphomyeloid HSC origin of SF3B1 mutations in MDS-RS patients and provide a novel in vivo platform for mechanistically and therapeutically exploring SF3B1 mutated MDS-RS. © 2017 by The American Society of Hematology.

  12. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    International Nuclear Information System (INIS)

    Minegishi, Yoshiki; Sakai, Yasuo; Yahara, Yasuhito; Akiyama, Haruhiko; Yoshikawa, Hideki; Hosokawa, Ko; Tsumaki, Noriyuki

    2014-01-01

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1 Δchon cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone

  13. Cyp26b1 within the growth plate regulates bone growth in juvenile mice

    Energy Technology Data Exchange (ETDEWEB)

    Minegishi, Yoshiki [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Department of Plastic and Reconstructive Surgery, University of Fukui Hospital, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakai, Yasuo [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Plastic Surgery, Bellland General Hospital, 500-3 Higashiyama Naka-ku, Sakai, Osaka 599-8247 (Japan); Yahara, Yasuhito [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Akiyama, Haruhiko [Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, 1-1 Yanagito, Gifu 501-1194 (Japan); Yoshikawa, Hideki [Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Hosokawa, Ko [Department of Plastic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsumaki, Noriyuki, E-mail: ntsumaki@cira.kyoto-u.ac.jp [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Japan Science and Technology Agency, CREST, Tokyo 102-0075 (Japan)

    2014-11-07

    Highlights: • Retinoic acid and Cyp26b1 were oppositely localized in growth plate cartilage. • Cyp26b1 deletion in chondrocytes decreased bone growth in juvenile mice. • Cyp26b1 deletion reduced chondrocyte proliferation and growth plate height. • Vitamin A-depletion partially reversed growth plate abnormalities caused by Cyp26b1 deficiency. • Cyp26b1 regulates bone growth by controlling chondrocyte proliferation. - Abstract: Retinoic acid (RA) is an active metabolite of vitamin A and plays important roles in embryonic development. CYP26 enzymes degrade RA and have specific expression patterns that produce a RA gradient, which regulates the patterning of various structures in the embryo. However, it has not been addressed whether a RA gradient also exists and functions in organs after birth. We found localized RA activities in the diaphyseal portion of the growth plate cartilage were associated with the specific expression of Cyp26b1 in the epiphyseal portion in juvenile mice. To disturb the distribution of RA, we generated mice lacking Cyp26b1 specifically in chondrocytes (Cyp26b1{sup Δchon} cKO). These mice showed reduced skeletal growth in the juvenile stage. Additionally, their growth plate cartilage showed decreased proliferation rates of proliferative chondrocytes, which was associated with a reduced height in the zone of proliferative chondrocytes, and closed focally by four weeks of age, while wild-type mouse growth plates never closed. Feeding the Cyp26b1 cKO mice a vitamin A-deficient diet partially reversed these abnormalities of the growth plate cartilage. These results collectively suggest that Cyp26b1 in the growth plate regulates the proliferation rates of chondrocytes and is responsible for the normal function of the growth plate and growing bones in juvenile mice, probably by limiting the RA distribution in the growth plate proliferating zone.

  14. Liver kinase B1 inhibits the expression of inflammation-related genes postcontraction in skeletal muscle.

    Science.gov (United States)

    Chen, Ting; Moore, Timothy M; Ebbert, Mark T W; McVey, Natalie L; Madsen, Steven R; Hallowell, David M; Harris, Alexander M; Char, Robin E; Mackay, Ryan P; Hancock, Chad R; Hansen, Jason M; Kauwe, John S; Thomson, David M

    2016-04-15

    Skeletal muscle-specific liver kinase B1 (LKB1) knockout mice (skmLKB1-KO) exhibit elevated mitogen-activated protein kinase (MAPK) signaling after treadmill running. MAPK activation is also associated with inflammation-related signaling in skeletal muscle. Since exercise can induce muscle damage, and inflammation is a response triggered by damaged tissue, we therefore hypothesized that LKB1 plays an important role in dampening the inflammatory response to muscle contraction, and that this may be due in part to increased susceptibility to muscle damage with contractions in LKB1-deficient muscle. Here we studied the inflammatory response and muscle damage with in situ muscle contraction or downhill running. After in situ muscle contractions, the phosphorylation of both NF-κB and STAT3 was increased more in skmLKB1-KO vs. wild-type (WT) muscles. Analysis of gene expression via microarray and RT-PCR shows that expression of many inflammation-related genes increased after contraction only in skmLKB1-KO muscles. This was associated with mild skeletal muscle fiber membrane damage in skmLKB1-KO muscles. Gene markers of oxidative stress were also elevated in skmLKB1-KO muscles after contraction. Using the downhill running model, we observed significantly more muscle damage after running in skmLKB1-KO mice, and this was associated with greater phosphorylation of both Jnk and STAT3 and increased expression of SOCS3 and Fos. In conclusion, we have shown that the lack of LKB1 in skeletal muscle leads to an increased inflammatory state in skeletal muscle that is exacerbated by muscle contraction. Increased susceptibility of the muscle to damage may underlie part of this response. Copyright © 2016 the American Physiological Society.

  15. Slice profile and B1 corrections in 2D magnetic resonance fingerprinting.

    Science.gov (United States)

    Ma, Dan; Coppo, Simone; Chen, Yong; McGivney, Debra F; Jiang, Yun; Pahwa, Shivani; Gulani, Vikas; Griswold, Mark A

    2017-11-01

    The goal of this study is to characterize and improve the accuracy of 2D magnetic resonance fingerprinting (MRF) scans in the presence of slice profile (SP) and B 1 imperfections, which are two main factors that affect quantitative results in MRF. The SP and B 1 imperfections are characterized and corrected separately. The SP effect is corrected by simulating the radiofrequency pulse in the dictionary, and the B 1 is corrected by acquiring a B 1 map using the Bloch-Siegert method before each scan. The accuracy, precision, and repeatability of the proposed method are evaluated in phantom studies. The effects of both SP and B 1 imperfections are also illustrated and corrected in the in vivo studies. The SP and B 1 corrections improve the accuracy of the T 1 and T 2 values, independent of the shape of the radiofrequency pulse. The T 1 and T 2 values obtained from different excitation patterns become more consistent after corrections, which leads to an improvement of the robustness of the MRF design. This study demonstrates that MRF is sensitive to both SP and B 1 effects, and that corrections can be made to improve the accuracy of MRF with only a 2-s increase in acquisition time. Magn Reson Med 78:1781-1789, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  16. SR-B1 Is a Silica Receptor that Mediates Canonical Inflammasome Activation

    Directory of Open Access Journals (Sweden)

    Misato Tsugita

    2017-01-01

    Full Text Available The inhalation of silica dust is associated with fibrosis and lung cancer, which are triggered by macrophage inflammatory responses; however, how macrophages recognize silica remains largely unknown. Here, we identify by functional expression cloning the class B scavenger receptor SR-B1 as a silica receptor. Through an extracellular α-helix, both mouse and human SR-B1 specifically recognized amorphous and crystalline silica, but not titanium dioxide nanoparticles, latex nanoparticles, or monosodium urate crystals, although all particles exhibited negative surface potentials. Genetic deletion of SR-B1 and masking of SR-B1 by monoclonal antibodies showed that SR-B1-mediated recognition of silica is associated with caspase-1-mediated inflammatory responses in mouse macrophages and human peripheral blood monocytes. Furthermore, SR-B1 was involved in silica-induced pulmonary inflammation in mice. These results indicate that SR-B1 is a silica receptor associated with canonical inflammasome activation.

  17. No significant effect of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid.

    Science.gov (United States)

    Xiang, Xiaoqiang; Vakkilainen, Juha; Backman, Janne T; Neuvonen, Pertti J; Niemi, Mikko

    2011-11-01

    To investigate possible effects of the SLCO1B1 polymorphism on the pharmacokinetics of ursodeoxycholic acid (UDCA) and its metabolites in healthy volunteers. In a crossover study with two phases, 15 healthy volunteers with the SLCO1B1*1A/*1A genotype, seven with the *1B/*1B genotype, and five with the *15/*15 or *5/*15 genotype ingested placebo or a single 150-mg dose of UDCA. Plasma concentrations of bile acids and their biosynthesis marker were determined up to 24 h post-ingestion by liquid chromatography-tandem mass spectrometry. The SLCO1B1 genotype had no significant effect on the pharmacokinetics of UDCA. The geometric mean ratios (95% confidence interval) of UDCA area under the plasma concentration-time curve from 0 to 12 h (AUC(0-12)) in subjects with the SLCO1B1*1B/*1B genotype and in subjects with the SLCO1B1*15/*15 or *5/*15 genotype to the AUC(0-12) in subjects with the SLCO1B1*1A/*1A genotype were 1.07 (0.85, 1.35; P = 0.459) and 0.93 (0.75, 1.15; P = 0.563), respectively. In addition, following either placebo or UDCA administration, the SLCO1B1 polymorphism showed no association with the AUC(0-24) of the glycine and taurine conjugates of UDCA, with endogenous bile acids, or with the incremental AUC(0-24) of a bile acid synthesis marker. Compared with placebo, UDCA ingestion increased the AUC(0-24) of cholic acid, glycochenodeoxycholic acid, glycocholic acid, and glycodeoxycholic acid by 1.5-, 1.1-, 1.2-, and 1.2- fold (P acids.

  18. Contribution of CYP1B1 mutations and founder effect to primary congenital glaucoma in Mexico.

    Science.gov (United States)

    Zenteno, Juan Carlos; Hernandez-Merino, Elena; Mejia-Lopez, Herlinda; Matías-Florentino, Margarita; Michel, Norma; Elizondo-Olascoaga, Celia; Korder-Ortega, Vincent; Casab-Rueda, Homero; Garcia-Ortiz, Jose Elias

    2008-01-01

    The frequency of primary congenital glaucoma (PCG)-causing CYP1B1 mutations varies importantly among distinct populations, ranging from 20% in Indonesians and Japanese to about 100% among the Saudi Arabians and Slovakian Gypsies. Thus, the molecular characterization of large groups of PCG from different ethnic backgrounds is important to establish the actual CYP1B1 contribution in specific populations. In this work, the molecular analysis of the CYP1B1 gene in a group of Mexican PCG patients is reported. Thirty unrelated Mexican patients fulfilling the clinical criteria for PCG were included. Two cases were familial and with proven consanguinity, originating from distinct regions of the country. Polymerase chain reaction amplification and direct automated sequencing of the CYP1B1 coding region was performed in each participating subject. An identical pathogenic CYP1B1 mutation was demonstrated in 2 unrelated PCG subjects. The mutation consisted of a homozygous G to A transition at nucleotide position 1505 in exon 3, which predicted a substitution of glutamic acid for lysine at residue 387 of the protein (E387K). In the remaining 28 PCG subjects, no deleterious mutations were identified. Both subjects with the E387K mutation shared a same haplotype for 5 CYP1B1 intragenic single nucleotide polymorphisms, indicating a common origin of the allele. Mexican patients with PCG are rarely (less than 10%) due to CYP1B1 mutations. Available data indicate that most of the non-Brazilian Latin American PCG patients investigated to date are not due to CYP1B1 defects. Populations with low incidence of CYP1B1 mutations are appropriate candidates for the identification of novel PCG-causing genes.

  19. Diversity in peptide recognition by the SH2 domain of SH2B1.

    Science.gov (United States)

    McKercher, Marissa A; Guan, Xiaoyang; Tan, Zhongping; Wuttke, Deborah S

    2018-02-01

    SH2B1 is a multidomain protein that serves as a key adaptor to regulate numerous cellular events, such as insulin, leptin, and growth hormone signaling pathways. Many of these protein-protein interactions are mediated by the SH2 domain of SH2B1, which recognizes ligands containing a phosphorylated tyrosine (pY), including peptides derived from janus kinase 2, insulin receptor, and insulin receptor substrate-1 and -2. Specificity for the SH2 domain of SH2B1 is conferred in these ligands either by a hydrophobic or an acidic side chain at the +3 position C-terminal to the pY. This specificity for chemically disparate species suggests that SH2B1 relies on distinct thermodynamic or structural mechanisms to bind to peptides. Using binding and structural strategies, we have identified unique thermodynamic signatures for each peptide binding mode, and several SH2B1 residues, including K575 and R578, that play distinct roles in peptide binding. The high-resolution structure of the SH2 domain of SH2B1 further reveals conformationally plastic protein loops that may contribute to the ability of the protein to recognize dissimilar ligands. Together, numerous hydrophobic and electrostatic interactions, in addition to backbone conformational flexibility, permit the recognition of diverse peptides by SH2B1. An understanding of this expanded peptide recognition will allow for the identification of novel physiologically relevant SH2B1/peptide interactions, which can contribute to the design of obesity and diabetes pharmaceuticals to target the ligand-binding interface of SH2B1 with high specificity. © 2017 Wiley Periodicals, Inc.

  20. Aflatoxin B1 adsorption by the natural aluminosilicates - concentrate of montmorillonite and zeolite

    Directory of Open Access Journals (Sweden)

    Marković Marija A.

    2016-01-01

    Full Text Available Aflatoxin B1 adsorption by the concentrate of bentonite clay - montmorillonite and the natural zeolite - clinoptilolite and was investigated at the initial toxin concentration 4 ppm, with different amonunts of solid phase in suspension (10, 5, 2 and 1 mg/10 mL and different pH values - 3, 7 and 9. Results indicated that for both minerals, decreasing the amount of solid phase in suspension, decrease the amount of active sites relevant for adsorption of aflatoxin B1. Thus, for concentrate of montnorillonite, at the lowest level of solid phase in suspension (1 mg/10 mL, aflatoxin B1 adsorption indexes were 97% at pH 3, 88% at pH 7 and 82% at pH 9, while for the natural zeolite, adsorption of toxin was 9% at pH 3 and 7% at pH 7 and 9. Since inorganic cations in minerals are mainly responsible for aflatoxin B1 adsorption, even the natural zeolite - clinoptilite has much higher cation exchange capacity (the content of inorganic exchangeable cations compared to the concentrate of montmorillonite, adsorption of aflatoxin B1 by this mineral is much lower. Comparing the molecular dimensions of aflatoxin B1 molecule with the dimension of channels of clinoptilolite and interlamellar space of montmorillonite it is obvious that this toxin is adsorbed only at the external surface of clinoptilolite while in the montmorillonite all active sites are equally available for its adsorption. Thus, the concentrate of montmorillonite posess by higher adsorption capacity for aflatoxin B1. Results presented in this paper confirmed the fact the differences in the structure of minerals led to their different efficiency for adsorption of aflatoxin B1. Mineralogical and chemical composition, determination of cation exchange capacity, etc., are very important parameters influencing the effectiveness of minerals as aflatoxin B1 adsorbents. [Projekat Ministarstva nauke Republike Srbije, br. 451-03-2802-IP Tip1/142, br. 172018 i br. 34013

  1. CYP1B1 Mutations in Individuals With Primary Congenital Glaucoma and Residing in Denmark

    DEFF Research Database (Denmark)

    Grønskov, Karen; Redó-Riveiro, Alba; Sandfeld, Lisbeth

    2016-01-01

    Primary congenital glaucoma (PCG OMIM 231300) can be caused by pathogenic sequence variations in cytochrome P450, subfamily 1, polypeptide 1 (CYP1B1). The purpose of this study was to investigate the contribution of sequence variations in CYP1B1 in a cohort of individuals with PCG residing...... mutations, 5 of which were novel. The frequency of CYP1B1 mutations in this cohort was comparable with other populations. We also detected an individual heterozygous for p.(Tyr81Asn) mutation, previously suggested to cause autosomal dominant primary open-angle glaucoma....

  2. EphB1 as a Novel Drug Target to Combat Pain and Addiction

    Science.gov (United States)

    2016-09-01

    Award Number: W81XWH-14-1-0220 Project Title: EphB1 as a Novel Drug Target to Combat Pain and Addiction Principal Investigator Name: Mark...Pain and Addiction 5a. CONTRACT NUMBER EphB1 as a Novel Drug Target to Combat Pain and Addiction 5b. GRANT NUMBER W81XWH-14-1-0220 5c. PROGRAM...SUBJECT TERMS Chronic neuropathic pain, opioid addiction , synaptic plasticity, EphB1 receptor, ephrin-B2, NMDA receptor, drug discovery 16. SECURITY

  3. Alternative Thieno[3,2-b][1]benzothiophene Isoindigo Polymers for Solar Cell Applications

    KAUST Repository

    Neophytou, Marios; Bryant, Daniel; Lopatin, Sergei; Chen, Hu; Hallani, Rawad K.; Cater, Lewis; McCulloch, Iain; Yue, Wan

    2018-01-01

    This work reports the synthesis, characterization, photophysical, and photovoltaic properties of five new thieno[3,2-b][1]benzothiophene isoindigo (TBTI)-containing low bandgap donor-acceptor conjugated polymers with a series of comonomers

  4. Potential of lactic acid fermentation in reducing aflatoxin B1 in ...

    African Journals Online (AJOL)

    African Journal of Food, Agriculture, Nutrition and Development ... Although maize is known to be highly susceptible to aflatoxin contamination, and a ... on reduction of aflatoxin B1 in Tanzania maize-based gruel (togwa) by four monocultures ...

  5. Polymorphisms in sh2b1 and spns1 loci are associated with ...

    Indian Academy of Sciences (India)

    SH2B1, which encodes a signal transduction adaptor protein ... Here, we studied the associa- tion of eight single ... Health Study (NSPHS) cohort, consisting of 719 individuals ... mate can lower triglyceride levels, and elevate high-density.

  6. Data of evolutionary structure change: 1EP8B-1FAAA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1EP8B-1FAAA 1EP8 1FAA B A -------------GGSVIVIDSKAAWDAQLAKGKEEHKP...IVVAFTATWCGPCKMIAPLFETLSNDYAGKVIFLKVDVD-AVAAVAEAAGITAMPTFHVYKDGVKADDLVGASQDKLKALVAKHAAA LELALGT.../pdbChain> 1FAAA KLDCNQENKTL EEE HHH 1 1FAA A 1FAAA

  7. Data of evolutionary structure change: 1AY4B-1YAAA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AY4B-1YAAA 1AY4 1YAA B A ---MLGNLKPQ-----LALMGEFRADPRQGKIDLGVGVY...LPVQTYRYFDAETRGVDFEGMKADLAAAKKGDMVLLHGCCHNPTGANLTLDQWAEIASILEKTGALPLIDLAYQGFGD-GLEEDAAGTRLIASRIP---EVLIAASCS...ntryChain> 1YAA A 1YAAA...ID> A 1YAAA QGFATGDLDKD

  8. Data of evolutionary structure change: 1EP7B-1FAAA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1EP7B-1FAAA 1EP7 1FAA B A -------------GGSVIVIDSKAAWDAQLAKGKEEHKP...IVVDFTATWCGPCKMIAPLFETLSNDYAGKVIFLKVD-VDAVAAVAEAAGITAMPTFHVYKDGVKADDLVGASQDKLKALVAKHAAA LELALGT...AA A 1FAAA FLKLDCNQENK A 1FAAA VTEVN-KDTFW

  9. CYP1B1 and myocilin gene mutations in Egyptian patients with ...

    African Journals Online (AJOL)

    Mahmoud R. Fassad

    2016-08-09

    Aug 9, 2016 ... Abstract Purpose: Primary congenital glaucoma (PCG) accounts for 26–29% of childhood ... Conclusion: The current study further endorses the role of CYP1B1 mutations in the etiology of ..... There is no conflict of interest.

  10. The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model.

    Directory of Open Access Journals (Sweden)

    Georgia Schäfer

    2009-12-01

    Full Text Available The interaction between Mycobacterium tuberculosis (Mtb and host cells is complex and far from being understood. The role of the different receptor(s implicated in the recognition of Mtb in particular remains poorly defined, and those that have been found to have activity in vitro were subsequently shown to be redundant in vivo.To identify novel receptors involved in the recognition of Mtb, we screened a macrophage cDNA library and identified scavenger receptor B class 1 (SR-B1 as a receptor for mycobacteria. SR-B1 has been well-described as a lipoprotein receptor which mediates both the selective uptake of cholesteryl esters and the efflux of cholesterol, and has also recently been implicated in the recognition of other pathogens. We show here that mycobacteria can bind directly to SR-B1 on transfected cells, and that this interaction could be inhibited in the presence of a specific antibody to SR-B1, serum or LDL. We define a variety of macrophage populations, including alveolar macrophages, that express this receptor, however, no differences in the recognition and response to mycobacteria were observed in macrophages isolated from SR-B1(-/- or wild type mice in vitro. Moreover, when wild type and SR-B1(-/- animals were infected with a low dose of Mtb (100 CFU/mouse there were no alterations in survival, bacterial burdens, granuloma formation or cytokine production in the lung. However, significant reduction in the production of TNF, IFNgamma, and IL10 were observed in SR-B1(-/- mice following infection with a high dose of Mtb (1000 CFU/mouse, which marginally affected the size of inflammatory foci but did not influence bacterial burdens. Deficiency of SR-B1 also had no effect on resistance to disease under conditions of varying dietary cholesterol. We did observe, however, that the presence of high levels of cholesterol in the diet significantly enhanced the bacterial burdens in the lung, but this was independent of SR-B1.SR-B1 is involved in

  11. Stability of aflatoxin B1 in animal feed candidate reference materials

    NARCIS (Netherlands)

    Roos, A.H.; Mazijk, van R.J.; Tuinstra, L.G.M.T.; Huf, F.A.

    1991-01-01

    Two candidate reference materials animal feed were stored at a temperature of -18°C, 4 C, 20°C and 37°C. The stability of aflatoxin B1 was studied duringa period of two years. A significant decrease in the aflatoxin B1 content was measured in the samples stared at 20°C and 37°C. In the samples

  12. The Potent of Aspergillus parasiticus to Produce Aflatoxin B1 on the Maize Flour During Storage

    Directory of Open Access Journals (Sweden)

    Agus Selamat Duniaji

    2016-03-01

    Full Text Available Aflatoxin B1 contamination caused by Aspergillus parasiticus and Aspergiluus Aspergillus flavus is a great concern in maize production worldwide. A. parasiticus infection and aflatoxin B1 contamination are usually found in maize and their processed during storage, distribution and processing. Aflatoxin B1 contamination in food and feed can cause the cancer diseases in animal and human. This research was aimed to determinate the potency of A. parasiticus to produce aflatoxin B1 in maize during storage 0, 5, 10 and 15 days. The research methods was using Completed Random Design (CRD with three replicated. The research was investigation of a number of colony A. parasiticus in Petato Dextro Agar (PDA and Aflatoxin B1 content by using Enzym Linked Immunosorbant Assay (ELISA. Result of research showed that A.parasiticus were susceptible to grow in maize flour and produce aflatoxin B1 during storage. The population of A. parasiticus in maize flour were  9.5 x 105 d in primary storage (0 days that was the total colony were increasing  .7 x 106 (storage 5 days, 2.5 x 107 (storage 10 days and 1.5 x 108 cfu/g with storage 15 days A. parasiticus was a potent to produce aflatoxin B1 in myzena flour with total of aflatoxin B1 is  66.50 ppb of mayzena flour during storage 5 days , 46.40 ppb with 10 days storage, 57.00 ppb during storage 15 days and was not found in 0 days.

  13. 26 CFR 1.1402(b)-1 - Self-employment income.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 12 2010-04-01 2010-04-01 false Self-employment income. 1.1402(b)-1 Section 1... (CONTINUED) INCOME TAXES Tax on Self-Employment Income § 1.1402(b)-1 Self-employment income. (a) In general... this section, the term “self-employment income” means the net earnings from self-employment derived by...

  14. Transcriptional regulation of male-sterility in 7B-1 male-sterile tomato mutant.

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    Vahid Omidvar

    Full Text Available The 7B-1 tomato (Solanum lycopersicum L. cv Rutgers is a male-sterile mutant with enhanced tolerance to abiotic stress, which makes it a potential candidate for hybrid seed breeding and stress engineering. To underline the molecular mechanism regulating the male-sterility in 7B-1, transcriptomic profiles of the 7B-1 male-sterile and wild type (WT anthers were studied using mRNA sequencing (RNA-Seq. In total, 768 differentially expressed genes (DEGs were identified, including 132 up-regulated and 636 down-regulated transcripts. Gene ontology (GO enrichment analysis of DEGs suggested a general impact of the 7B-1 mutation on metabolic processes, such as proteolysis and carbohydrate catabolic process. Sixteen candidates with key roles in regulation of anther development were subjected to further analysis using qRT-PCR and in situ hybridization. Cytological studies showed several defects associated with anther development in the 7B-1 mutant, including unsynchronized anther maturation, dysfunctional meiosis, arrested microspores, defect in callose degradation and abnormal tapetum development. TUNEL assay showed a defect in programmed cell death (PCD of tapetal cells in 7B-1 anthers. The present study provides insights into the transcriptome of the 7B-1 mutant. We identified several genes with altered expression level in 7B-1 (including beta-1,3 glucanase, GA2oxs, cystatin, cysteine protease, pectinesterase, TA29, and actin that could potentially regulate anther developmental processes, such as meiosis, tapetum development, and cell-wall formation/degradation.

  15. Code-B-1 for stress/strain calculation for TRISO fuel particle (Contract research)

    International Nuclear Information System (INIS)

    Aihara, Jun; Ueta, Shohei; Shibata, Taiju; Sawa, Kazuhiro

    2011-12-01

    We have developed Code-B-1 for the prediction of the failure probabilities of the coated fuel particles for the high temperature gas-cooled reactors (HTGRs) under operation by modification of an existing code. A finite element method (FEM) is employed for the stress calculation part and Code-B-1 can treat the plastic deformation of the coating layer of the coated fuel particles which the existing code cannot treat. (author)

  16. Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0152 TITLE: Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-14-1-0152 Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism... chromatin immunoprecipitation-next generation DNA sequencing (ChIP-seq) and integrative network modeling to identify the SAFB1 cistrome and the extent of

  17. LytB1 and LytB2 of Mycobacterium tuberculosis Are Not Genetically Redundant.

    Directory of Open Access Journals (Sweden)

    Amanda Claire Brown

    Full Text Available Mycobacterium tuberculosis synthesises isoprenoid precursors via the MEP/DOXP pathway and at least five enzymes in the pathway (Dxs1, Dxr/IspC, IspD, IspF, and GcpE/IspG are required for growth in vitro. We investigated the role of LytB (IspH in M. tuberculosis; M. tuberculosis is unusual in that it has two homologs-LytB1 and LytB2. We were unable to delete the lytB2 gene unless we provided an additional copy elsewhere, demonstrating that this is the essential homolog. We expressed lytB1 from the lytB2 promoter and confirmed that this could not complement for loss of function of lytB2, despite LytB1 possessing all the previously described conserved critical residues. Interestingly the sole LytB homolog of Mycobacterium smegmatis was able to compensate for loss of LytB2 in M. tuberculosis. We tested translational fusions of LytB1 and LytB2 for functionality in M. tuberculosis, but only a fusion with 90% N-terminal LytB2 and 10% C-terminal LytB1 was functional. In order to identify the key difference between the two proteins, site directed mutagenesis was used to change LytB2 residues into their counterparts in LytB1. None of these amino acid substitutions was essential for function and all lytB2 mutant alleles were functional. In contrast, mutation of the key residues for [Fe4S4] cluster formation, as well as a catalytic residue in LytB1 did not result in functional complementation. Thus, although LytB1 and LytB2 are not genetically redundant, this is not dependent on small amino acid changes, but is likely to be a result of major overall structural differences.

  18. (B1-/sup 125/I-desaminotyrosine)-insulin - A novel homogeneous insulin tracer

    Energy Technology Data Exchange (ETDEWEB)

    Bahrami, S; Zahn, H; Brandenburg, D [Deutsches Wollforschungsinstitut, Aachen (Germany F.R.); Machulla, H -J; Dutschka, K [Institut fuer Medizinische Strahlenphysik und Strahlenbiologie des Universitaetsklinikum, Essen (Germany F.R.)

    1980-10-28

    (B1-/sup 125/I-desaminotyrosine)-insulin (/sup 125/I-MII) was prepared with high specific activities (420 Ci/mmole) by exchanging B1-phenylalanine for /sup 125/I-p-hydroxyphenyl-propionic acid N-hydroxysuccinimide ester (Bolton-Hunter reagent). Overall radiochemical yields were about 8%. Analytical quality control and purification were performed by means of radio high pressure liquid chromatography. The radiochemical purity of /sup 125/I-MII was >99%, and the immunoprecipitability was 97%.

  19. Residues of Avermectin B1a in rotational crops and soils following soil treatment with [14C]Avermectin B1a

    International Nuclear Information System (INIS)

    Moye, H.A.; Malagodi, M.H.; Yoh, H.; Leibee, G.L.; Ku, C.C.; Wislocki, P.G.

    1987-01-01

    [ 14 C]Avermectin B 1 a was applied twelve times to muck and sandy loam soils and three times to sandy soil at 0.025-0.030 lb/acre per application. These applications simulated the intended use of avermectin B 1 a on celery, vegetables, and cotton, respectively. Following three aging periods in each soil type, sorghum, lettuce, and carrot or turnip seeds were planted and harvested at one-fourth, half, and full size. Analysis of these crops by oxidative combustion demonstrated that crops grown in muck, sandy loam, and sandy soils contained radiolabeled residues ranging from below the limit of quantitation (BLQ) to 7.4 μg/kg of avermectin B 1 a equivalents, BLQ to 11.6 μg/kg, and BLQ to 3.54 μg/kg, respectively. There was a general trend of decreasing residue concentrations with increasing preharvest intervals in crops grown in all soils. The radioactivity present in muck and sandy loam soils disappeared with half-lives ranging from 103 to 267 days and from 102 to 132 days, respectively

  20. Dependence of B1+ and B1- Field Patterns of Surface Coils on the Electrical Properties of the Sample and the MR Operating Frequency.

    Science.gov (United States)

    Vaidya, Manushka V; Collins, Christopher M; Sodickson, Daniel K; Brown, Ryan; Wiggins, Graham C; Lattanzi, Riccardo

    2016-02-01

    In high field MRI, the spatial distribution of the radiofrequency magnetic ( B 1 ) field is usually affected by the presence of the sample. For hardware design and to aid interpretation of experimental results, it is important both to anticipate and to accurately simulate the behavior of these fields. Fields generated by a radiofrequency surface coil were simulated using dyadic Green's functions, or experimentally measured over a range of frequencies inside an object whose electrical properties were varied to illustrate a variety of transmit [Formula: see text] and receive [Formula: see text] field patterns. In this work, we examine how changes in polarization of the field and interference of propagating waves in an object can affect the B 1 spatial distribution. Results are explained conceptually using Maxwell's equations and intuitive illustrations. We demonstrate that the electrical conductivity alters the spatial distribution of distinct polarized components of the field, causing "twisted" transmit and receive field patterns, and asymmetries between [Formula: see text] and [Formula: see text]. Additionally, interference patterns due to wavelength effects are observed at high field in samples with high relative permittivity and near-zero conductivity, but are not present in lossy samples due to the attenuation of propagating EM fields. This work provides a conceptual framework for understanding B 1 spatial distributions for surface coils and can provide guidance for RF engineers.

  1. Suppression of gastric cancer dissemination by ephrin-B1-derived peptide.

    Science.gov (United States)

    Tanaka, Masamitsu; Kamata, Reiko; Yanagihara, Kazuyoshi; Sakai, Ryuichi

    2010-01-01

    Interaction of the Eph family of receptor protein tyrosine kinases and their ligands, ephrin family members, induces bidirectional signaling through cell-cell contacts. High expression of B-type ephrin is associated with high invasion potential of tumors, and we previously observed that signaling through the C-terminus of ephrin-B1 mediates the migration and invasion of cells, and is involved in the promotion of carcinomatous peritonitis in vivo. Here we show that the intracellular introduction of a synthetic peptide derived from ephrin-B1 C-terminus blocks ephrin-B1 mediated signaling in scirrhous gastric cancer cells. Treatment of cancer cells with a fusion peptide consisting of HIV-TAT and amino acids 331-346 of ephrin-B1 (PTD-EFNB1-C) suppressed the activation of RhoA, mediated by the association of ephrin-B1 with an adaptor protein Dishevelled, and also inhibited extracellular secretion of metalloproteinase. Moreover, injection of PTD-EFNB1-C peptide into the peritoneal cavity of nude mice suppressed carcinomatous peritonitis of intraperitoneally transplanted scirrhous gastric cancer cells. These results indicate the possible application of ephrin-B1 C-terminal peptide to develop novel protein therapy for scirrhous gastric carcinoma, especially in the stage of tumor progression, including peritoneal dissemination.

  2. Silencing of Atp2b1 increases blood pressure through vasoconstriction.

    Science.gov (United States)

    Shin, Young-Bin; Lim, Ji Eun; Ji, Su-Min; Lee, Hyeon-Ju; Park, So-Yon; Hong, Kyung-Won; Lim, Mihwa; McCarthy, Mark I; Lee, Young-Ho; Oh, Bermseok

    2013-08-01

    Recent genome-wide association studies (GWASs) have identified 30 genetic loci that regulate blood pressure, increasing our understanding of the cause of hypertension. However, it has been difficult to define the causative genes at these loci due to a lack of functional analyses. In this study, we aimed to validate the candidate gene ATP2B1 in 12q21, variants near which have the strongest association with blood pressure in Asians and Europeans. ATP2B1 functions as a calcium pump to fine-tune calcium concentrations - necessary for repolarization following muscular contractions. We silenced Atp2b1 using an siRNA complex, injected into mouse tail veins. In treated mice, blood pressure rose and the mesenteric arteries increased in wall : lumen ratio. Moreover, the arteries showed enhanced myogenic responses to pressure, and contractile responses to phenylephrine increased compared with the control, suggesting that blood pressure is regulated by ATP2B1 through the contraction and dilation of the vessel, likely by controlling calcium concentrations in the resting state. These results support that ATP2B1 is the causative gene in the blood pressure-associated 12q21 locus and demonstrate that ATP2B1 expression in the vessel influences blood pressure.

  3. A Novel Role for C5a in B-1 Cell Homeostasis

    Directory of Open Access Journals (Sweden)

    Katharina Bröker

    2018-02-01

    Full Text Available B-1 cells constitute a unique subpopulation of lymphocytes residing mainly in body cavities like the peritoneal cavity (PerC but are also found in spleen and bone marrow (BM. As innate-like B cells, they mediate first line immune defense through low-affinity natural IgM (nIgM antibodies. PerC B-1 cells can egress to the spleen and differentiate into nIgM antibody-secreting plasma cells that recognize conserved exogenous and endogenous cellular structures. Homing to and homeostasis within the PerC are regulated by the chemokine CXCL13 released by PerC macrophages and stroma cells. However, the exact mechanisms underlying the regulation of CXCL13 and B-1 homeostasis are not fully explored. B-1 cells play important roles in the inflammatory response to infection, autoimmunity, ischemia/reperfusion injury, obesity, and atherosclerosis. Remarkably, this list of inflammatory entities has a strong overlap with diseases that are regulated by complement suggesting a link between B-1 cells and the complement system. Interestingly, up to now, no data exist regarding the role of complement in B-1 cell biology. Here, we demonstrate for the first time that C5a regulates B-1 cell steady-state dynamics within the peritoneum, the spleen, and the BM. We found decreased B-1a cell numbers in the peritoneum and the spleen of C5aR1−/− mice associated with increased B1-a and B1-b numbers in the spleen and high serum titers of nIgM antibodies directed against phosphorylcholine and several pneumococcal polysaccharides. Similarly, peritoneal B-1a cells were decreased in the peritoneum and splenic B-1a and B-1b cells were increased in C5aR2−/− mice. The decrease in peritoneal B-1 cell numbers was associated with decreased peritoneal CXCL13 levels in C5aR1−/− and C5aR2−/− mice. In search for mechanisms, we found that combined TLR2 and IL-10 receptor activation in PerC macrophages induced strong CXCL13 production, which was significantly reduced in cells

  4. Expansion of B-1a cells with germline heavy chain sequence in lupus mice

    Directory of Open Access Journals (Sweden)

    Nichol E Holodick

    2016-03-01

    Full Text Available B6.Sle1.Sle2.Sle3 (B6.TC lupus-prone mice carrying the NZB allele of Cdkn2c, encoding for the cyclin-dependent kinase inhibitor P18INK4, accumulate B-1a cells due to a higher rate of proliferative self-renewal. However, it is unclear whether this affects primarily early appearing B-1a cells of fetal origin or later appearing B-1a cells that emerge from bone marrow. B-1a cells are the major source of natural autoantibodies, and it has been shown that their protective nature is associated with a germline-like sequence, which is characterized by few N-nucleotide insertions and a repertoire skewed towards rearrangements predominated during fetal life, VH11 and VH12. To determine the nature of B-1a cells expanded in B6.TC mice, we amplified immunoglobulin genes by PCR from single cells in mice. Sequencing showed a significantly higher proportion of B-1a cell antibodies display fewer N-additions in B6.TC mice than in B6 control mice. Following this lower number of N-insertions within the CDR-H3 region, the B6.TC B-1a cells display shorter CDR-H3 length than B6 B-1a cells. The absence of N-additions is a surrogate for fetal origin, as TdT expression starts after birth in mice. Therefore, our results suggest that the B-1a cell population is not only expanded in autoimmune B6.TC mice but also qualitatively different with the majority of cells from fetal origin. Accordingly, our sequencing results also demonstrated overuse of VH11 and VH12 in autoimmune B6.TC mice as compared to B6 controls. These results suggest that the development of lupus autoantibodies in these mice is coupled with skewing of the B-1a cell repertoire and possible retention of protective natural antibodies.

  5. Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments

    KAUST Repository

    Quteineh, Lina; Vandenberghe, Frederik; Saigi Morgui, Nuria; Delacré taz, Auré lie; Choong, Eva; Gholam-Rezaee, Mehdi; Magistretti, Pierre J.; Bondolfi, Guido; Von Gunten, Armin; Preisig, Martin A.; Castelao, Enrique; Vollenweider, Peter; Waeber, Gé rard; Bochud, Murielle; Kutalik, Zoltá n; Conus, Philippe O.; Eap, Chin Bin

    2015-01-01

    Background Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11β-HSD1 may lead to the development of MetS. Methods We investigated the association between seven HSD11B1 gene (encoding 11β-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n=478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (n R1 =168, n R2 =188) and in several large population-based samples (n 1 =5338; n 2 =123 865; n 3 >100 000). Results HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (P corrected <0.05). These associations were exclusively detected in women (n=257) with more than 3.1 kg/m 2, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (P corrected <0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (P corrected =0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, P corrected =0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples. Conclusions Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not

  6. RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats.

    Directory of Open Access Journals (Sweden)

    B Alex Merrick

    Full Text Available Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1, a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG than microarray analysis, including low copy and novel transcripts related to AFB1's carcinogenic activity compared to feed controls (CTRL. Paired-end reads were mapped to the rat genome (Rn4 with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005 compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT's on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c

  7. RNA-Seq profiling reveals novel hepatic gene expression pattern in aflatoxin B1 treated rats.

    Science.gov (United States)

    Merrick, B Alex; Phadke, Dhiral P; Auerbach, Scott S; Mav, Deepak; Stiegelmeyer, Suzy M; Shah, Ruchir R; Tice, Raymond R

    2013-01-01

    Deep sequencing was used to investigate the subchronic effects of 1 ppm aflatoxin B1 (AFB1), a potent hepatocarcinogen, on the male rat liver transcriptome prior to onset of histopathological lesions or tumors. We hypothesized RNA-Seq would reveal more differentially expressed genes (DEG) than microarray analysis, including low copy and novel transcripts related to AFB1's carcinogenic activity compared to feed controls (CTRL). Paired-end reads were mapped to the rat genome (Rn4) with TopHat and further analyzed by DESeq and Cufflinks-Cuffdiff pipelines to identify differentially expressed transcripts, new exons and unannotated transcripts. PCA and cluster analysis of DEGs showed clear separation between AFB1 and CTRL treatments and concordance among group replicates. qPCR of eight high and medium DEGs and three low DEGs showed good comparability among RNA-Seq and microarray transcripts. DESeq analysis identified 1,026 differentially expressed transcripts at greater than two-fold change (p<0.005) compared to 626 transcripts by microarray due to base pair resolution of transcripts by RNA-Seq, probe placement within transcripts or an absence of probes to detect novel transcripts, splice variants and exons. Pathway analysis among DEGs revealed signaling of Ahr, Nrf2, GSH, xenobiotic, cell cycle, extracellular matrix, and cell differentiation networks consistent with pathways leading to AFB1 carcinogenesis, including almost 200 upregulated transcripts controlled by E2f1-related pathways related to kinetochore structure, mitotic spindle assembly and tissue remodeling. We report 49 novel, differentially-expressed transcripts including confirmation by PCR-cloning of two unique, unannotated, hepatic AFB1-responsive transcripts (HAfT's) on chromosomes 1.q55 and 15.q11, overexpressed by 10 to 25-fold. Several potentially novel exons were found and exon refinements were made including AFB1 exon-specific induction of homologous family members, Ugt1a6 and Ugt1a7c. We find the

  8. Biochemical attributes of Hens Fed Irradiated Aflatoxin B1 Contamination Diet

    International Nuclear Information System (INIS)

    Farag, M.D.E.H.; Abdul Azeem, A.M.; Abdalla, E.A.; Ahmed, N.A.H.

    2017-01-01

    The purpose of this study is to evaluate the effect of feeding diet artificially contaminated with aflatoxin B 1(AFB1) at level 0.2 mg kg"-"1 AFB1, and gamma (γ) irradiated (10, 20, and 30 kGy) on reducing the deleterious effects of laying hens Golden Montaza (GM) biochemical attributes. These include liver weight, AFB1 liver residue content, AST, ALT, ALP, creatinine, total proteins, albumin and globulin, as well as, the levels of T3, T4, TSH, FSH, LH, progesterone hormone and hepatic histology. At 38 week of age, groups of laying hens were fed on a normal non-contaminated diet (G1), aflatoxin-contaminated diet (G2), and irradiated contaminated diets (G3, G4 and G5) for 3 weeks, as a duration period. When the hens reached 42 weeks of age, they were fed on normal diet for 3 weeks, as a recovery period. Results showed that AST, ALT, ALP, and creatinine significantly increased in AFs treated groups in comparison with those received AFs-containing diet and irradiated up to 30 kGy. Layers fed contaminated diet of AFB1 suffered from a lower level of total proteins, albumin and globulin. Meanwhile, the results showed that the level of serum T4 was lower, but conversely the levels of FSH were higher for those fed on diets contaminated with AFB1 compared to those fed irradiated contaminated diets with AFB1, no significant change occurred in serum blood T3, TSH, LH and progesterone in all tested groups. Treated contaminated diets with γ-irradiation at 30 kGy reduced the incidence and severity of hepatic histology. The 30 kGy radiation dose was more effective, in this respect, in all biochemical indices. For recovery period diets non-contaminated with AFB1, the results showed improvements in all biochemical indices and recovered the hepatic structure with increasing the recovery period especially for those fed on irradiated diets through the experimental duration. In conclusion, feeding of diets contaminated with AFB1 altered the blood profiles, and damaged the liver

  9. Incidência de fumonisina B1, aflatoxinas B1, B2, G1 e G2, ocratoxina A e zearalenona em produtos de milho Occurrence of fumonisin B1, aflatoxins B1, B2, G1, and G2, ochratoxin A and zearalenone in corn products

    Directory of Open Access Journals (Sweden)

    Luciane Mie Kawashima

    2006-09-01

    Full Text Available Levantamentos de ocorrência de micotoxinas em alimentos foram realizados nas últimas duas décadas nas regiões Sudeste e Sul do Brasil. Levantamentos em alimentos comercializados em outras regiões têm-se limitado a aflatoxinas em amendoim e castanhas do Brasil. O presente trabalho pesquisou a presença de fumonisina B1, aflatoxinas B1, B2, G1 e G2, ocratoxina A e zearalenona em 74 amostras de produtos a base de milho adquiridas no comércio da cidade de Recife, PE, durante o período de 1999 a 2001. Fumonisina B1 foi determinada por cromatografia líquida de alta eficiência com detecção por fluorescência e as demais toxinas foram determinadas por cromatografia em camada delgada. Fumonisina B1 foi encontrada em 94,6% das amostras em concentrações variando de 20 a 8600 µg/kg. Apenas 5 amostras continham aflatoxina B1 e o teor máximo encontrado foi 20 µg/kg. Duas amostras ultrapassaram o limite de 20 µg/kg para a somatória das aflatoxinas B1, B2, G1 e G2 (farinha de milho pré-cozida com 21,5 µg/kg e quirera (xerém com 23,3 µg/kg. As aflatoxinas G1 e G2, ocratoxina A e zearalenona não foram detectadas em nenhuma das amostras. Todas as amostras contaminadas com aflatoxinas também apresentaram fumonisina B1.Research concerning the presence of mycotoxin in food has been conducted in the Southwest and South regions of Brazil over the last two decades. Research in other regions has been limited to aflatoxin in peanuts and Brazil nuts. The aim of this work is to study the presence of fumonisin B1, aflatoxins B1, B2, G1, and G2, ochratoxin A and zearalenone in 74 samples of corn products acquired in shops and food markets in the city of Recife (PE from 1999 to 2001. Fumonisin B1 was determined by high performance liquid chromatography and fluorescence was detected. The other toxins were determined by thin layer chromatography. Fumonisin B1 was found in 94.6% of the samples in levels from 20 to 8600 µg/kg. Only 5 samples contained

  10. Germline recombination in a novel Cre transgenic line, Prl3b1-Cre mouse.

    Science.gov (United States)

    Al-Soudy, Al-Sayed; Nakanishi, Tsuyoshi; Mizuno, Seiya; Hasegawa, Yoshikazu; Shawki, Hossam H; Katoh, Megumi C; Basha, Walaa A; Ibrahim, Abdelaziz E; El-Shemy, Hany A; Iseki, Hiroyoshi; Yoshiki, Atsushi; Hiromori, Youhei; Nagase, Hisamitsu; Takahashi, Satoru; Oishi, Hisashi; Sugiyama, Fumihiro

    2016-07-01

    Spermatogenesis is a complex and highly regulated process by which spermatogonial stem cells differentiate into spermatozoa. To better understand the molecular mechanisms of the process, the Cre/loxP system has been widely utilized for conditional gene knockout in mice. In this study, we generated a transgenic mouse line that expresses Cre recombinase under the control of the 2.5 kbp of the Prolactin family 3, subfamily b, member 1 (Prl3b1) gene promoter (Prl3b1-cre). Prl3b1 was initially reported to code for placental lactogen 2 (PL-2) protein in placenta along with increased expression toward the end of pregnancy. PL-2 was found to be expressed in germ cells in the testis, especially in spermatocytes. To analyze the specificity and efficiency of Cre recombinase activity in Prl3b1-cre mice, the mice were mated with reporter R26GRR mice, which express GFP ubiquitously before and tdsRed exclusively after Cre recombination. The systemic examination of Prl3b1-cre;R26GRR mice revealed that tdsRed-positive cells were detected only in the testis and epididymis. Fluorescence imaging of Prl3b1-cre;R26GRR testes suggested that Cre-mediated recombination took place in the germ cells with approximately 74% efficiency determined by in vitro fertilization. In conclusion, our results suggest that the Prl3b1-cre mice line provides a unique resource to understand testicular germ-cell development. genesis 54:389-397, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Scavenger receptor B1 facilitates macrophage uptake of silver nanoparticles and cellular activation

    Energy Technology Data Exchange (ETDEWEB)

    Aldossari, Abdullah A.; Shannahan, Jonathan H. [The University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (United States); Podila, Ramakrishna [Clemson University, Department of Physics and Astronomy (United States); Brown, Jared M., E-mail: jared.brown@ucdenver.edu [The University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (United States)

    2015-07-15

    Due to increased use of silver nanoparticles (AgNPs) for their antimicrobial activity, concerns have risen regarding potential adverse human health effects. Scavenger receptor B1 (SR-B1), a major receptor for high-density lipoprotein (HDL), is expressed by macrophages and has also been reported to play a role in recognition of negatively charged particles. We, therefore, hypothesized that SR-B1 mediates macrophage uptake of AgNPs and inflammatory activation. To test this hypothesis, we exposed a mouse macrophage cell line RAW264.7 (RAW) and bone marrow-derived macrophages (BMDM) to 20 nm citrate-suspended AgNPs. To verify the role of the SR-B1 receptor, we utilized a SR-B1 inhibitor (Blt2). In vitro studies demonstrated uptake of AgNPs and HDL-coated AgNPs by macrophages which were significantly reduced following pretreatment with Blt2. Inflammatory cytokine arrays revealed that macrophages exposed to AgNPs up-regulated expression of Tnf-α, Oncostatin m (OSM), Ccl4, Il17f, Ccl7, and Ccl2, whereas Il16 was found to be down-regulated. Macrophage activation was observed following AgNP and HDL-coated AgNP exposure as measured by OSM protein production and increased surface expression of CD86. These markers of activation were reduced with Blt2 pretreatment. The in vitro findings were confirmed in vivo through pulmonary instillation of AgNPs in mice. Pulmonary instillation of AgNPs resulted in a recruitment of inflammatory cells that were reduced in SR-B1-deficient mice or following Blt2 pretreatment. This study suggests that SR-B1 plays a major role in cellular recognition of AgNPs and the induction of cell responses that could contribute to inflammation caused by AgNP exposure.

  12. Scavenger receptor B1 facilitates macrophage uptake of silver nanoparticles and cellular activation

    Science.gov (United States)

    Aldossari, Abdullah A.; Shannahan, Jonathan H.; Podila, Ramakrishna; Brown, Jared M.

    2015-07-01

    Due to increased use of silver nanoparticles (AgNPs) for their antimicrobial activity, concerns have risen regarding potential adverse human health effects. Scavenger receptor B1 (SR-B1), a major receptor for high-density lipoprotein (HDL), is expressed by macrophages and has also been reported to play a role in recognition of negatively charged particles. We, therefore, hypothesized that SR-B1 mediates macrophage uptake of AgNPs and inflammatory activation. To test this hypothesis, we exposed a mouse macrophage cell line RAW264.7 (RAW) and bone marrow-derived macrophages (BMDM) to 20 nm citrate-suspended AgNPs. To verify the role of the SR-B1 receptor, we utilized a SR-B1 inhibitor (Blt2). In vitro studies demonstrated uptake of AgNPs and HDL-coated AgNPs by macrophages which were significantly reduced following pretreatment with Blt2. Inflammatory cytokine arrays revealed that macrophages exposed to AgNPs up-regulated expression of Tnf- α, Oncostatin m (OSM), Ccl4, Il17f, Ccl7, and Ccl2, whereas Il16 was found to be down-regulated. Macrophage activation was observed following AgNP and HDL-coated AgNP exposure as measured by OSM protein production and increased surface expression of CD86. These markers of activation were reduced with Blt2 pretreatment. The in vitro findings were confirmed in vivo through pulmonary instillation of AgNPs in mice. Pulmonary instillation of AgNPs resulted in a recruitment of inflammatory cells that were reduced in SR-B1-deficient mice or following Blt2 pretreatment. This study suggests that SR-B1 plays a major role in cellular recognition of AgNPs and the induction of cell responses that could contribute to inflammation caused by AgNP exposure.

  13. EphrinB1 expression is dysregulated and promotes oncogenic signaling in medulloblastoma.

    Science.gov (United States)

    McKinney, Nicole; Yuan, Liangping; Zhang, Hongying; Liu, Jingbo; Cho, Yoon-Jae; Rushing, Elisabeth; Schniederjan, Matthew; MacDonald, Tobey J

    2015-01-01

    Eph receptors and ephrin ligands are master regulators of oncogenic signaling required for proliferation, migration, and metastasis. Yet, Eph/ephrin expression and activity in medulloblastoma (MB), the most common malignant brain tumor of childhood, remains poorly defined. We hypothesized that Eph/ephrins are differentially expressed by sonic hedgehog (SHH) and non-SHH MB and that specific members contribute to the aggressive phenotype. Affymetrix gene expression profiling of 29 childhood MB, separated into SHH (N = 11) and non-SHH (N = 18), was performed followed by protein validation of selected Eph/ephrins in another 60 MB and two MB cell lines (DAOY, D556). Functional assays were performed using MB cells overexpressing or deleted for selected ephrins. We found EPHB4 and EFNA4 almost exclusively expressed by SHH MB, whereas EPHA2, EPHA8, EFNA1 and EFNA3 are predominantly expressed by non-SHH MB. The remaining family members, except EFNB1, are ubiquitously expressed by over 70-90 % MB, irrespective of subgroup. EFNB1 is the only member differentially expressed by 28 % of SHH and non-SHH MB. Corresponding protein expression for EphB/ephrinB1 and B2 was validated in MB. Only ephrinB2 was also detected in fetal cerebellum, indicating that EphB/ephrinB1 expression is MB-specific. EphrinB1 immunopositivity localizes to tumor cells within MB with the highest proliferative index. EphrinB1 overexpression promotes EphB activation, alters F-actin distribution and morphology, decreases adhesion, and significantly promotes proliferation. Either silencing or overexpression of ephrinB1 impairs migration. These results indicate that EphrinB1 is uniquely dysregulated in MB and promotes oncogenic responses in MB cells, implicating ephrinB1 as a potential target.

  14. Electronic structures of B1 MoN, fcc Mo2N, and hexagonal MoN

    International Nuclear Information System (INIS)

    Ihara, H.; Kimura, Y.; Senzaki, K.; Kezuka, H.; Hirabayashi, M.

    1985-01-01

    The electronic structures of B1 MoN, fcc Mo 2 N, and hexagonal MoN were observed by photoelectron spectroscopic measurement. The B1-MoN phase has been predicted to be a high-T/sub c/ superconductor because of a large density of states at Fermi level. The observed electronic structure of the stoichiometric B1-MoN phase is different from that of the real B1-MoN type. The nitrogen excess B1-MoN/sub x/ (x> or =1.3) phase, however, shows the B1-type electronic structure. This is explained by the occurrence of a nitrogen vacancy in the apparent stoichiometric B1 phase and the occupation of the nitrogen vacancy in the nitrogen-excess B1 phase. This property is related to the previously reported low T/sub c/ of the B1-MoN crystals

  15. Prenatal exposure to aflatoxin B1: developmental, behavioral, and reproductive alterations in male rats

    Science.gov (United States)

    Supriya, Ch.; Reddy, P. Sreenivasula

    2015-06-01

    Previous studies have shown that aflatoxin B1 (AfB1) inhibits androgen biosynthesis as a result of its ability to form a high-affinity complex with the steroidogenic acute regulatory protein. The results of the present study demonstrate the postnatal effects of in utero exposure to AfB1 in the rat. Pregnant Wistar rats were given 10, 20, or 50 μg AfB1/kg body weight daily from gestation day (GD) 12 to GD 19. At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. Male pups from control and AfB1-exposed animals were weaned and maintained up to postnatal day (PD) 100. Litter size, birth weight, sex ratio, survival rate, and crown-rump length of the pups were significantly decreased in AfB1-exposed rats when compared to controls. Elapsed time (days) for testes to descend into the scrotal sac was significantly delayed in experimental pups when compared to control pups. Behavioral observations such as cliff avoidance, negative geotaxis, surface rightening activity, ascending wire mesh, open field behavior, and exploratory and locomotory activities were significantly impaired in experimental pups. Body weights and the indices of testis, cauda epididymis, prostate, seminal vesicles, and liver were significantly reduced on PD 100 in male rats exposed to AfB1 during embryonic development when compared with controls. Significant reduction in the testicular daily sperm production, epididymal sperm count, and number of viable, motile, and hypo-osmotic tail coiled sperm was observed in experimental rats. The levels of serum testosterone and activity levels of testicular hydroxysteroid dehydrogenases were significantly decreased in a dose-dependent manner with a significant increase in the serum follicle-stimulating hormone and luteinizing hormone in experimental rats. Deterioration in the testicular and cauda epididymal architecture was observed in experimental rats. The results of fertility

  16. B-1 cells modulate the murine macrophage response to Leishmania major infection.

    Science.gov (United States)

    Arcanjo, Angelica F; Nunes, Marise P; Silva-Junior, Elias B; Leandro, Monique; da Rocha, Juliana Dutra Barbosa; Morrot, Alexandre; Decote-Ricardo, Debora; Freire-de-Lima, Celio Geraldo

    2017-05-26

    To investigate the modulatory effect of B-1 cells on murine peritoneal macrophages infected with Leishmania major ( L. major ) in vitro . Peritoneal macrophages obtained from BALB/c and BALB/c XID mice were infected with L. major and cultured in the presence or absence of B-1 cells obtained from wild-type BALB/c mice. Intracellular amastigotes were counted, and interleukin-10 (IL-10) production was quantified in the cellular supernatants using an enzyme-linked immunosorbent assay. The levels of the lipid mediator prostaglandin E2 (PGE 2 ) were determined using a PGE 2 enzyme immunoassay kit (Cayman Chemical, Ann Arbor, MI), and the number of lipid bodies was quantified in the cytoplasm of infected macrophages in the presence and absence of B-1 cells. Culturing the cells with selective PGE 2 -neutralizing drugs inhibited PGE 2 production and confirmed the role of this lipid mediator in IL-10 production. In contrast, we demonstrated that B-1 cells derived from IL-10 KO mice did not favor the intracellular growth of L. major . We report that B-1 cells promote the growth of L. major amastigotes inside peritoneal murine macrophages. We demonstrated that the modulatory effect was independent of physical contact between the cells, suggesting that soluble factor(s) were released into the cultures. We demonstrated in our co-culture system that B-1 cells trigger IL-10 production by L. major -infected macrophages. Furthermore, the increased secretion of IL-10 was attributed to the presence of the lipid mediator PGE 2 in supernatants of L. major -infected macrophages. The presence of B-1 cells also favors the production of lipid bodies by infected macrophages. In contrast, we failed to obtain the same effect on parasite replication inside L. major -infected macrophages when the B-1 cells were isolated from IL-10 knockout mice. Our results show that elevated levels of PGE 2 and IL-10 produced by B-1 cells increase L. major growth, as indicated by the number of parasites in cell

  17. Rapid pretreatment and detection of trace aflatoxin B1 in traditional soybean sauce.

    Science.gov (United States)

    Xie, Fang; Lai, WeiHua; Saini, Jasdeep; Shan, Shan; Cui, Xi; Liu, DaoFeng

    2014-05-01

    Soybean sauce, a traditional fermented food in China, has different levels of aflatoxin B1 pollution. Two kinds of direct and indirect immunomagnetic bead methods for the pretreatment of aflatoxin B1 were evaluated in this work. A method was established to detect aflatoxin B1 in soybean sauce using an immunomagnetic bead system for pretreatment and ELISA for quantification. The pretreatment method of immunomagnetic beads performed better compared with the conventional extraction and immunoaffinity column method. ELISA exhibited a good linear relationship at an aflatoxin B1 concentration of 0.05-0.3μg/kg (r(2)=0.9842). The average recoveries across spike levels varied from 0.5 to 7μg/kg were 83.6-104% with a relative standard deviation between 4.2% and 11.7%. With the advantages of rapid detection, easy operation, simple equipment, sensitivity, accuracy, and high recovery; this method can be well applied in the trace determination of aflatoxin B1 in soybean sauce samples. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers.

    Science.gov (United States)

    Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako; Chen, Xin; Wersto, Robert; Sen, Ranjan; Young, Howard A; Croft, Michael; Ferrucci, Luigi; Biragyn, Arya

    2016-04-15

    B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL(+)MHC class-I(Hi)CD86(Hi)B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. They induce expression and activation of 4-1BBL and IFN-γR1 on B1a cells to subsequently upregulate membrane TNF-α and CD86. As a result, activated B1a/4BL cells induce expression of granzyme B in CD8(+)T cells by targeting TNFR2 via membrane TNF-α and providing costimulation with CD86. Thus, for the first time, to our knowledge, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8(+)T cells. Copyright © 2016 by The American Association of Immunologists, Inc.

  19. Evaluation of aflatoxin B1 in different parts of pistachio fruit and effects of processing stages

    Directory of Open Access Journals (Sweden)

    R Dargahi

    2014-11-01

    Full Text Available Pistachio nut as the most important agricultural export products is facing challenges trough production and conception. Toxigenic Aspergillus species are able to grow and produce dangerous mycotoxins on pistachio nut. Distribution of aflatoxin in different pistachio samples collected pre- (early splitting and healthy pistachios in orchards and post-harvest (steps in processing plants was evaluated. Aflatoxin B1 content of samples was quantified using ELISA.  Overall, high content of aflatoxin B1 in pre-harvest was observed in early splitting pistachios which were 5 times higher than healthy ones. The mean value of aflatoxin B1 content in early splitting and healthy pistachio was 10.2 and 1.8 ng/g, respectively. In processing plant, the content of aflatoxin B1 in stained, small, floater and open shell pistachios was 21, 4, 15 and 2 times higher than unstained, large, sinker and closed shell pistachios, respectively. The presence of aflatoxin B1 in samples taken from orchards and processing plants indicates pre-harvest contamination by aflatoxin-producing fungi, which may exacerbate by inadequate post-harvest conditions. Physical properties of contaminated pistachios may be used to reduce aflatoxin levels in pistachio bulks during or after processing. ELISA, as practical, sensitive and cheap method, may apply to determine the aflatoxin content of pistachios.

  20. Impact of aflatoxin B1 on the pharmacokinetic disposition of enrofloxacin in broiler chickens.

    Science.gov (United States)

    Kalpana, Starling; Srinivasa Rao, G; Malik, Jitendra K

    2015-09-01

    The potential impact of subchronic exposure of aflatoxin B1 was investigated on the pharmacokinetic disposition of enrofloxacin in broiler chickens. Broiler chickens given either normal or aflatoxin B1 (750μg/kg diet) supplemented diet for 6 weeks received a single oral dose of enrofloxacin (10mg/kg body wt). Blood samples were drawn from the brachial vein at predetermined time intervals after drug administration. Enrofloxacin plasma concentrations analyzed by RP-HPLC were significantly lower in aflatoxin B1-exposed broiler chickens at 0.167, 0.5 and 1.0h after drug administration. In aflatoxin B1-exposed broiler chickens, the absorption rate constant (ka) of enrofloxacin (0.20±0.05h(-1)) was significantly decreased as compared to the unexposed birds (0.98±0.31h(-1)). The values of [Formula: see text] , tmax and AUC0-∞ of enrofloxacin were nonsignificantly increased by 17%, 26% and 17% in aflatoxin-exposed broiler chickens, respectively. Subchronic aflatoxin B1 exposure markedly decreased the initial absorption of enrofloxacin without significantly influencing other pharmacokinetic parameters in broiler chickens. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Metabolism and incorporation of (14C)-Aflatoxin B1 in chicken embryos

    International Nuclear Information System (INIS)

    Miura, Toshiyuki

    1980-01-01

    The metabolism of 14 C-aflatoxin B 1 (Af. B 1 ) in the chick embryo was studied. When inoculated into air cells, the embryos, egg membranes, other parts of the eggs and the expired carbon dioxide during a 1 hour period contained 8.0, 15.0, 76.0 and 1.0% of the total detected radio-activity, respectively. In the case of yolk sac inoculation, the embryos, other parts of the eggs and the expired carbon dioxide during a 1 hour period contained 3.4, 96.4 and 0.2% of the total detected counts, respectively. At equal doses of ( 14 C)-Af. B 1 into the air cell and yolk sac of eggs, the embryos incorporated 14 C in a ratio of 2.5 : 1, which is similar to the ratio of LD 50 values (air cell inoculation = 0.41 mu g/egg; yolk sac inoculation = 0.89 mu g/egg) by the two inoculation routes. The homogenate of embryos inoculated with Af. B 1 was partitioned into chloroform and methanol-water. As the time after inoculation increased, methanol-water-soluble metabolites from Af. B 1 increased and chloroform-soluble ones decreased. Af. M 1 was the principal metabolite among the chloroform-soluble substances. (author)

  2. Volumetric B1 (+) mapping of the brain at 7T using DREAM.

    Science.gov (United States)

    Nehrke, Kay; Versluis, Maarten J; Webb, Andrew; Börnert, Peter

    2014-01-01

    To tailor and optimize the Dual Refocusing Echo Acquisition Mode (DREAM) approach for volumetric B1 (+) mapping of the brain at 7T. A new DREAM echo timing scheme based on the virtual stimulated echo was derived to minimize potential effects of transverse relaxation. Furthermore, the DREAM B1 (+) mapping performance was investigated in simulations and experimentally in phantoms and volunteers for volumetric applications, studying and optimizing the accuracy of the sequence with respect to saturation effects, slice profile imperfections, and T1 and T2 relaxation. Volumetric brain protocols were compiled for different isotropic resolutions (5-2.5 mm) and SENSE factors, and were studied in vivo for different RF drive modes (circular/linear polarization) and the application of dielectric pads. Volumetric B1 (+) maps with good SNR at 2.5 mm isotropic resolution were acquired in about 20 s or less. The specific absorption rate was well below the safety limits for all scans. Mild flow artefacts were observed in the large vessels. Moreover, a slight contrast in the ventricle was observed in the B1 (+) maps, which could be attributed to T1 and T2 relaxation effects. DREAM enables safe, very fast, and robust volumetric B1 (+) mapping of the brain at ultrahigh fields. Copyright © 2013 Wiley Periodicals, Inc.

  3. A decrease in cyclin B1 levels leads to polyploidization in DNA damage-induced senescence.

    Science.gov (United States)

    Kikuchi, Ikue; Nakayama, Yuji; Morinaga, Takao; Fukumoto, Yasunori; Yamaguchi, Naoto

    2010-05-04

    Adriamycin, an anthracycline antibiotic, has been used for the treatment of various types of tumours. Adriamycin induces at least two distinct types of growth repression, such as senescence and apoptosis, in a concentration-dependent manner. Cellular senescence is a condition in which cells are unable to proliferate further, and senescent cells frequently show polyploidy. Although abrogation of cell division is thought to correlate with polyploidization, the mechanisms underlying induction of polyploidization in senescent cells are largely unclear. We wished, therefore, to explore the role of cyclin B1 level in polyploidization of Adriamycin-induced senescent cells. A subcytotoxic concentration of Adriamycin induced polyploid cells having the features of senescence, such as flattened and enlarged cell shape and activated beta-galactosidase activity. In DNA damage-induced senescent cells, the levels of cyclin B1 were transiently increased and subsequently decreased. The decrease in cyclin B1 levels occurred in G2 cells during polyploidization upon treatment with a subcytotoxic concentration of Adriamycin. In contrast, neither polyploidy nor a decrease in cyclin B1 levels was induced by treatment with a cytotoxic concentration of Adriamycin. These results suggest that a decrease in cyclin B1 levels is induced by DNA damage, resulting in polyploidization in DNA damage-induced senescence.

  4. Fetal Lymphoid Progenitors Become Restricted to B-1 Fates Coincident with IL-7Rα Expression.

    Directory of Open Access Journals (Sweden)

    Ryuji Iida

    Full Text Available B-1 cells represent a sub-fraction of B lymphocytes that participate in T cell-independent antibody production and contribute to innate immunity. While the production of B-1 cells is favored during the fetal waves of lymphopoiesis, it has been unclear when and how that differentiation option is specified. To clarify this, lymphoid and hematopoietic progenitors of fetal liver (FL and adult bone marrow (ABM were examined for the B cell differentiation potential. Mouse common lymphoid progenitors (CLPs and more primitive KSL fraction of FL and ABM were transferred to SCID mice and donor-derived B cell subsets were analyzed 4 weeks later. CLPs were also cultured on ST2 stromal cells for 6 days prior to transplantation. While Lin- IL-7Rα+ CLPs from ABM differentiated to B-1, B-2 and marginal zone B (MZB cells, equivalent cells from d15 FL differentiated mostly to B-1a cells. We found that fetal CLPs had less ability to colonize the bone marrow than adult CLPs. However, the fetal/adult difference was already present when progenitors were cultured in an identical condition before transplantation. More primitive KSL fraction of FL could generate the same broad spectrum of B cells typical of adults, including splenic MZB cells. In conclusion, we argue that FL and ABM-CLPs are intrinsically different regarding B-1/B-2 fates and the difference is acquired just before or coincident with the acquisition of IL-7Rα expression.

  5. L1-mediated retrotransposition of murine B1 and B2 SINEs recapitulated in cultured cells.

    Science.gov (United States)

    Dewannieux, Marie; Heidmann, Thierry

    2005-06-03

    SINEs are short interspersed nucleotide elements with transpositional activity, present at a high copy number (up to a million) in mammalian genomes. They are 80-400 bp long, non-coding sequences which derive either from the 7SL RNA (e.g. human Alus, murine B1s) or tRNA (e.g. murine B2s) polymerase III-driven genes. We have previously demonstrated that Alus very efficiently divert the enzymatic machinery of the autonomous L1 LINE (long interspersed nucleotide element) retrotransposons to transpose at a high rate. Here we show, using an ex vivo assay for transposition, that both B1 and B2 SINEs can be mobilized by murine LINEs, with the hallmarks of a bona fide retrotransposition process, including target site duplications of varying lengths and integrations into A-rich sequences. Despite different phylogenetic origins, transposition of the tRNA-derived B2 sequences is as efficient as that of the human Alus, whereas that of B1s is 20-100-fold lower despite a similar high copy number of these elements in the mouse genome. We provide evidence, via an appropriate nucleotide substitution within the B1 sequence in a domain essential for its intracellular targeting, that the current B1 SINEs are not optimal for transposition, a feature most probably selected for the host sake in the course of evolution.

  6. Encoding methods for B1+ mapping in parallel transmit systems at ultra high field

    Science.gov (United States)

    Tse, Desmond H. Y.; Poole, Michael S.; Magill, Arthur W.; Felder, Jörg; Brenner, Daniel; Jon Shah, N.

    2014-08-01

    Parallel radiofrequency (RF) transmission, either in the form of RF shimming or pulse design, has been proposed as a solution to the B1+ inhomogeneity problem in ultra high field magnetic resonance imaging. As a prerequisite, accurate B1+ maps from each of the available transmit channels are required. In this work, four different encoding methods for B1+ mapping, namely 1-channel-on, all-channels-on-except-1, all-channels-on-1-inverted and Fourier phase encoding, were evaluated using dual refocusing acquisition mode (DREAM) at 9.4 T. Fourier phase encoding was demonstrated in both phantom and in vivo to be the least susceptible to artefacts caused by destructive RF interference at 9.4 T. Unlike the other two interferometric encoding schemes, Fourier phase encoding showed negligible dependency on the initial RF phase setting and therefore no prior B1+ knowledge is required. Fourier phase encoding also provides a flexible way to increase the number of measurements to increase SNR, and to allow further reduction of artefacts by weighted decoding. These advantages of Fourier phase encoding suggest that it is a good choice for B1+ mapping in parallel transmit systems at ultra high field.

  7. Expression of cytochromes P450 1A1 and 1B1 in human lung from smokers, non-smokers, and ex-smokers

    International Nuclear Information System (INIS)

    Kim, James H.; Sherman, Mark E.; Curriero, Frank C.; Guengerich, F. Peter; Strickland, Paul T.; Sutter, Thomas R.

    2004-01-01

    Cytochromes P450 1A1 and 1B1 are known to bioactivate procarcinogens such as polycyclic aromatic hydrocarbons (PAHs) found in cigarette smoke and are inducible via an Ah receptor-mediated mechanism. The aim of this study was to examine the levels of expression of CYP1A1 and CYP1B1 in samples of lung from smokers (n = 18), non-smokers (n = 7), and ex-smokers (n = 7). Using immunoglobulin preparations of highly specific polyclonal antibodies and immunoblot analysis of microsomes from lung tissues, we determined the specific content for CYP1A1 and CYP1B1. For CYP1A1, we found median expression levels of 15.5 pmol/mg microsomal protein in smokers, 6.0 pmol/mg microsomal protein in non-smokers, and 19.0 pmol/mg microsomal protein in ex-smokers. The difference in median expression levels of smokers and ex-smokers compared to non-smokers was statistically significant. For CYP1B1, we found median expression levels of 1.8 pmol/mg microsomal protein in smokers, 1.0 pmol/mg microsomal protein in non-smokers, and 4.4 pmol/mg microsomal protein in ex-smokers. The difference in median expression levels between ex-smokers and non-smokers was statistically significant. These results suggest that levels of expression of CYP1A1 and CYP1B1 protein in lung tissues from smokers and ex-smokers are quantitatively greater than in non-smokers. By immunohistochemical analysis, we demonstrated the expression of CYP1A1 and CYP1B1 in normal human alveolar type I and II cells, ciliated columnar epithelial cells lining bronchoalveolar airways, and alveolar macrophages. These results confirm that CYP1A1 is expressed in normal human lung, appears to be induced in smokers, and show interindividual variation; the similar characteristics of CYP1B1 are demonstrated

  8. The structure and the analytical potential energy function of NH2 (X2B1)

    International Nuclear Information System (INIS)

    Liu Yufang; Jiang Lijuan; Ma Heng; Sun Jinfeng

    2008-01-01

    This paper reports that the equilibrium structure of NH 2 has been optimized at the QCISD/6-311++G (3df, 3pd) level. The ground-state NH 2 has a bent (C 2v , X 2 B 1 ) structure with an angle of 103.0582°. The geometrical structure is in good agreement with the other calculational and experimental results. The harmonic frequencies and the force constants have also been calculated. Based on the group theory and the principle of microscopic reversibility, the dissociation limits of NH 2 (C 2v , X 2 B 1 ) have been derived. The potential energy surface of NH 2 (X 2 B 1 ) is reasonable. The contour lines are constructed, the structure and energy of NH 2 reappear on the potential energy surface

  9. EphB1 as a Novel Drug Target to Combat Pain and Addiction

    Science.gov (United States)

    2015-09-01

    EphB1  as  a  Novel  Drug  Target  to  Combat  Pain  and   Addiction   Principal  Investigator  Name:   Mark...Principal  Investigator   Phone  and  Email:   Phone :  214-­‐645-­‐5916   Email:  Mark.Henkemeyer@UTSouthwestern.edu   Report  Date...31 Aug 2015 4. TITLE AND SUBTITLE EphB1 as a Novel Drug Target to Combat Pain and Addiction 5a. CONTRACT NUMBER EphB1 as a Novel Drug Target to

  10. Comparative analysis between P1 and B1 equations for neutron moderation

    International Nuclear Information System (INIS)

    Martinez, Aquilino Senra; Silva, Fernando Carvalho da; Cardoso, Carlos Eduardo Santos

    2000-01-01

    In order to calculate the neutron flux in nuclear reactors, B1 or P1 equations are solved by numerical methods for several groups of energy. The neutron fluxes obtained from the solutions of the B1 and P1 equations are similar when they are applied to large nuclear power reactors. However, an important difference between the two fluxes is that the system of P1 equations uses one more approximation than the B1 system and then, its flux is less precise. The present work shows the relations between both equations and analyzes for what conditions the two equations systems are equivalent. Furthermore, this equations are numerically solved in 54 groups of energy for a quadrangular arrange. (author)

  11. CT study of infantile cerebral vitamin B1 deficiency (analysis of 22 cases)

    International Nuclear Information System (INIS)

    Liu Bin; Xi Meifang; Wang Mengding; Wang Chaoxiu

    1998-01-01

    Purpose: To study the CT features of infantile cerebral vitamin B 1 deficiency. Methods: The authors retrospectively reviewed the clinical manifestations and CT findings of 22 cases of infantile vitamin B 1 deficiency. Results: The main clinical signs were seizure malaise dullness and vomiting. CT scans showed bilateral symmetrical hypodense foci in lenticular nucleus (20/22), head of caudate nucleus (15/22), thalamus (3/22), anterior limb of internal capsule (4/22), external capsule (1/22) and para-ventricle white matter (2/22), and in many cases, signs of cerebral atrophy. 22 cases received thiamine treatment and were fully recovered. Conclusion: The authors concluded that bilateral symmetric hypodense foci in lenticular nucleus thalamus, head of caudate nucleus, anterior limb of internal capsule, external capsule and para-ventricle white matter were important CT signs suggestive of infantile cerebral vitamin B 1 deficiency

  12. Production of aflatexin B1 in wheat grains under different environmental storage conditions

    International Nuclear Information System (INIS)

    Mahrous, S.R.; Shahin, A.A.M.; Bothaina, M.Y.

    2000-01-01

    Fungal flora of stored wheat grains and the production of aflatoxin B 1 by Aflavus in wheat grains under different environmental conditions were examined. Aspergillus, Penicillium,. Fusarium, Cladosporium, Curvularia, Epicouccum, Verticilium, Rhizopus, Mucor and Altenaria were the predominant fungi isolated from the collected non-disinfected grains. Aspergillus spp, were only isolated from surface disinfected grains. Of 223 aspergillus spp, isolates only 128 found to aflatoxin producing and all aflatoxin producing-fungi belonged to the Aflavus group. Results demonstrate that Aflavus could produce maximum concentration of aflatoxin B 1 in grains at 20% moisture (163.5 MOU g/kg). The highest concentration of aflatoxin B 1 was produced by Aflavus (10 5 spores/g) in wheat grains with 20% moisture after 20 days at 30 degree and 92.40 % R.H. The aflatoxin production did not increase monotonously as a function of inoculum density

  13. Prevalence of Virulent Escherichia coli Belonging B1 Phylogroup in Municipal Water Supply in Dhaka, Bangladesh

    DEFF Research Database (Denmark)

    Ferdous, Jannataul; Rashid, Ridwan Bin; Tulsiani, Suhella

    isolated from drinking water in Arichpur, a low income area of Dhaka, Bangladesh. The distribution of the phylogroups and virulence genes were investigated in 200 isolates among them 110 isolates were from municipal water supply system and 90 were from household drinking water. Gene profile of virulence.......001. Therefore, it can be inferred municipal water supply was a greater contributor of pathogenic E. coli from the B1 phylogroup. Usually commensals fall in the Phylogroups A and B1. The presence of greater number of virulent B1 phylogroup isolates originating from municipal water supply indicates......Escherichia coli is a commensal organism of the digestive tracts of many vertebrates, including humans. Contamination of drinking water with pathogenic E. coli is a serious public health concern. This study focused on the distribution of phylogenetic groups and virulence gene profile of E. coli...

  14. Fractionation of radioactivity in the milk of goats administered 14C-aflatoxin B1

    International Nuclear Information System (INIS)

    Goto, T.; Hsieh, D.P.

    1985-01-01

    A detailed fractionation of radioactivity in the milk of goats administered 14 C-aflatoxin B1 at low doses was performed. The milk collected in the first 24 h following dosing contained radioactivity equivalent to 0.45-1.1% of the dose given. The radioactivity in each sample was partitioned into 4 fractions: ether, protein, dichloromethane, and water-alcohol. Over 80% of the radioactivity was detected in the dichloromethane fraction, of which over 95% was attributable to aflatoxin M1. No aflatoxin B1 or other known aflatoxin metabolites were detected in any fraction. The results indicate that the major metabolite of aflatoxin B1 in goat milk is aflatoxin M1 and that other metabolites, including conjugates, are of minor significance

  15. B1 to B2 structural phase transition in LiF under pressure

    Science.gov (United States)

    Jain, Aayushi; Dixit, R. C.

    2018-05-01

    In the last few decades the alkali halides emerged as crystals with useful applications and their high-pressure behaviour is the most intensively studied subject in high-pressure physics/chemistry, material science, and geosciences. Most alkali halides follow the B1 (NaCl-type)→B2 (CsCl-type) phase-transition route under pressure. In the present paper, we have investigated the characteristics of structural phase transition that occurred in Lithium Florid compound under high pressure. The transition pressure of B1-B2 was calculated using an effective interionic interaction potential (EIOP). The changes of the characteristics of crystals like, Gibbs free energy, cohesive energy, volume collapse, and lattice constant are calculated for the B1 and B2 structures. These data were compared with the available experimental and theoretical data.

  16. Comparison of genetic variations of the SLCO1B1, SLCO1B3, and SLCO2B1 genes among five ethnic groups.

    Science.gov (United States)

    Namgoong, Suhg; Cheong, Hyun Sub; Kim, Ji On; Kim, Lyoung Hyo; Na, Han Sung; Koh, In Song; Chung, Myeon Woo; Shin, Hyoung Doo

    2015-11-01

    Organic anion-transporting polypeptide (OATP; gene symbol, SLCO) transporters are generally involved in the uptake of multiple drugs and their metabolites at most epithelial barriers. The pattern of single-nucleotide polymorphisms (SNPs) in these transporters may be determinants of interindividual variability in drug disposition and response. The objective of this study was to define the distribution of SNPs of three SLCO genes, SLCO1B1, SLCO1B3, and SLCO2B1, in a Korean population and other ethnic groups. The study was screened using the Illumina GoldenGate assay for genomic DNA from 450 interethnic subjects, including 11 pharmacogenetic core variants and 76 HapMap tagging SNPs. The genotype distribution of the Korean population was similar to East Asian populations, but significantly different from African American and European American cohorts. These interethnic differences will be useful information for prospective studies, including genetic association and pharmacogenetic studies of drug metabolism by SLCO families. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Hydrolysed fumonisin B1 and N-(deoxy-D-fructos-1-yl)-fumonisin B1: stability and catabolic fate under simulated human gastrointestinal conditions.

    Science.gov (United States)

    Cirlini, Martina; Hahn, Irene; Varga, Elisabeth; Dall'Asta, Margherita; Falavigna, Claudia; Calani, Luca; Berthiller, Franz; Del Rio, Daniele; Dall'Asta, Chiara

    2015-02-01

    Food processing may induce thermal degradation of fumonisins in corn via Maillard-type reactions, or alkaline hydrolysis via loss of the two tricarballylic acid moieties. In the former case, N-(1-deoxy-D-fructos-1-yl)-fumonisin B(1) (NDF) can be formed, while the latter derivative is called hydrolysed fumonisin B(1) (HFB(1)). The aim of this study was to deepen the knowledge about the gastrointestinal stability of HFB(1) and NDF in humans. Due to the lack of standard, NDF was chemically synthesised and cleaned up in high purity to be used for further experiments. While NDF is already partially cleaved (about 41%) during simulated digestion, it remained rather stable towards human colon microflora. In contrast to this, HFB(1) is partially metabolised by the colon microflora to unknown compounds after 24 h of fermentation, as seen by a loss of about 22%. Concluding, the cleavage of NDF during digestion as well as the likely metabolisation of HFB(1) emphasise the need for animal trials to ascertain their toxicity in vivo.

  18. EphB1 as a Novel Drug Target to Combat Pain and Addiction

    Science.gov (United States)

    2017-09-01

    AWARD NUMBER: W81XWH-14-1-0220 TITLE: EphB1 as a Novel Drug Target to Combat Pain and Addiction PRINCIPAL INVESTIGATOR: Mark Henkemeyer...as a Novel Drug Target to Combat Pain and Ad 5a. CONTRACT NUMBER EphB1 as a Novel Drug Target to Combat Pain and Addiction 5b. GRANT NUMBER W81XWH...neuronal and has functions in vascular endothelial cells. 6. We have also carried out computational analysis of potantial docking/binding of chemical

  19. Twitching motility and biofilm formation are associated with tonB1 in Xylella fastidiosa.

    Science.gov (United States)

    Cursino, Luciana; Li, Yaxin; Zaini, Paulo A; De La Fuente, Leonardo; Hoch, Harvey C; Burr, Thomas J

    2009-10-01

    A mutation in the Xylella fastidiosa tonB1 gene resulted in loss of twitching motility and in significantly less biofilm formation as compared with a wild type. The altered motility and biofilm phenotypes were restored by complementation with a functional copy of the gene. The mutation affected virulence as measured by Pierce's disease symptoms on grapevines. The role of TonB1 in twitching and biofilm formation appears to be independent of the characteristic iron-uptake function of this protein. This is the first report demonstrating a functional role for a tonB homolog in X. fastidiosa.

  20. Twitching motility and biofilm formation are associated with tonB1 in Xylella fastidiosa

    OpenAIRE

    Cursino, Luciana; Li, Yaxin; Zaini, Paulo A.; De La Fuente, Leonardo; Hoch, Harvey C.; Burr, Thomas J.

    2017-01-01

    A mutation in the Xylella fastidiosa tonB1 gene resulted in loss of twitching motility and in significantly less biofilm formation as compared with a wild type. The altered motility and biofilm phenotypes were restored by complementation with a functional copy of the gene. The mutation affected virulence as measured by Pierce's disease symptoms on grapevines. The role of TonB1 in twitching and biofilm formation appears to be independent of the characteristic iron-uptake function of this prote...

  1. Fate of Fumonisin B1 in Naturally Contaminated Corn during Ethanol Fermentation

    OpenAIRE

    Bothast, R. J.; Bennett, G. A.; Vancauwenberge, J. E.; Richard, J. L.

    1992-01-01

    Two lots of corn naturally contaminated with fumonisin B1 (15 and 36 ppm) and a control lot (no fumonisin B1 detected) were used as substrates for ethanol production in replicate 8.5-liter yeast fermentations. Ethanol yields were 8.8% for both the control and low-fumonisin corn, while the high-fumonisin corn contained less starch and produced 7.2% ethanol. Little degradation of fumonisin occurred during fermentation, and most was recovered in the distillers' grains, thin stillage, and distill...

  2. Studies on tridecaptin B(1), a lipopeptide with activity against multidrug resistant Gram-negative bacteria.

    Science.gov (United States)

    Cochrane, Stephen A; Lohans, Christopher T; van Belkum, Marco J; Bels, Manon A; Vederas, John C

    2015-06-07

    Previously other groups had reported that Paenibacillus polymyxa NRRL B-30507 produces SRCAM 37, a type IIA bacteriocin with antimicrobial activity against Campylobacter jejuni. Genome sequencing and isolation of antimicrobial compounds from this P. polymyxa strain show that the antimicrobial activity is due to polymyxins and tridecaptin B1. The complete structural assignment, synthesis, and antimicrobial profile of tridecaptin B1 is reported, as well as the putative gene cluster responsible for its biosynthesis. This peptide displays strong activity against multidrug resistant Gram-negative bacteria, a finding that is timely to the current problem of antibiotic resistance.

  3. Linkage of genes for laminin B1 and B2 subunits on chromosome 1 in mouse.

    Science.gov (United States)

    Elliott, R W; Barlow, D; Hogan, B L

    1985-08-01

    We have used cDNA clones for the B1 and B2 subunits of laminin to find restriction fragment length DNA polymorphisms for the genes encoding these polypeptides in the mouse. Three alleles were found for LamB2 and two for LamB1 among the inbred mouse strains. The segregation of these polymorphisms among recombinant inbred strains showed that these genes are tightly linked in the central region of mouse Chromosome 1 between Sas-1 and Ly-m22, 7.4 +/- 3.2 cM distal to the Pep-3 locus. There is no evidence in the mouse for pseudogenes for these proteins.

  4. Biotechnological Fluorescent Ligands of the Bradykinin B1 Receptor: Protein Ligands for a Peptide Receptor.

    Directory of Open Access Journals (Sweden)

    Xavier Charest-Morin

    Full Text Available The bradykinin (BK B1 receptor (B1R is a peculiar G protein coupled receptor that is strongly regulated to the point of being inducible in immunopathology. Limited clinical evidence suggests that its expression in peripheral blood mononuclear cells is a biomarker of active inflammatory states. In an effort to develop a novel imaging/diagnostic tool, we report the rational design and testing of a fusion protein that is a ligand of the human B1R but not likely to label peptidases. This ligand is composed of a fluorescent protein (FP (enhanced green FP [EGFP] or mCherry prolonged at its N-terminus by a spacer peptide and a classical peptide agonist or antagonist (des-Arg9-BK, [Leu8]des-Arg9-BK, respectively. The design of the spacer-ligand joint peptide was validated by a competition assay for [3H]Lys-des-Arg9-BK binding to the human B1R applied to 4 synthetic peptides of 18 or 19 residues. The labeling of B1R-expressing cells with EGFP or mCherry fused with 7 of such peptides was performed in parallel (microscopy. Both assays indicated that the best design was FP-(Asn-Glyn-Lys-des-Arg9-BK; n = 15 was superior to n = 5, suggesting benefits from minimizing steric hindrance between the FP and the receptor. Cell labeling concerned mostly plasma membranes and was inhibited by a B1R antagonist. EGFP-(Asn-Gly15-Lys-des-Arg9-BK competed for the binding of [3H]Lys-des-Arg9-BK to human recombinant B1R, being only 10-fold less potent than the unlabeled form of Lys-des-Arg9-BK to do so. The fusion protein did not label HEK 293a cells expressing recombinant human BK B2 receptors or angiotensin converting enzyme. This study identifies a modular C-terminal sequence that can be adapted to protein cargoes, conferring high affinity for the BK B1R, with possible applications in diagnostic cytofluorometry, histology and drug delivery (e.g., in oncology.

  5. A New Orbit for Comet C/1865 B1 (Great Southern Comet of 1865)

    Science.gov (United States)

    Branham, Richard L., Jr.

    2018-04-01

    Comet C/1865 B1 (Great southern comet of 1865), observed only in the southern hemisphere, is one of a large number of comets with parabolic orbits. Given that there are 202 observations in right ascension and 165 in declination it proves possible to calculate a better orbit than that Körber published in 1887, the orbit used in various catalogs and data bases. C/1865 B1's orbit is hyperbolic and statistically distinguishable from a parabola. This object, therefore, cannot be considered an NEO. The comet has a small perihelion distance of 0.026 AU.

  6. SH2B1 regulation of energy balance, body weight, and glucose metabolism

    OpenAIRE

    Rui, Liangyou

    2014-01-01

    The Src homology 2B (SH2B) family members (SH2B1, SH2B2 and SH2B3) are adaptor signaling proteins containing characteristic SH2 and PH domains. SH2B1 (also called SH2-B and PSM) and SH2B2 (also called APS) are able to form homo- or hetero-dimers via their N-terminal dimerization domains. Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins, including Janus kinase 2 (JAK2), TrkA, insulin receptors, insulin-like growth factor-1 receptors, insulin receptor substrate-1 (IRS1), and...

  7. Potential Antioxidant Role of Tridham in Managing Oxidative Stress against Aflatoxin-B1-Induced Experimental Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Vijaya Ravinayagam

    2012-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most fatal cancers due to delayed diagnosis and lack of effective treatment options. Significant exposure to Aflatoxin B1 (AFB1, a potent hepatotoxic and hepatocarcinogenic mycotoxin, plays a major role in liver carcinogenesis through oxidative tissue damage and p53 mutation. The present study emphasizes the anticarcinogenic effect of Tridham (TD, a polyherbal traditional medicine, on AFB1-induced HCC in male Wistar rats. AFB1-administered HCC-bearing rats (Group II showed increased levels of lipid peroxides (LPOs, thiobarbituric acid substances (TBARs, and protein carbonyls (PCOs and decreased levels of enzymic and nonenzymic antioxidants when compared to control animals (Group I. Administration of TD orally (300 mg/kg body weight/day for 45 days to HCC-bearing animals (Group III significantly reduced the tissue damage accompanied by restoration of the levels of antioxidants. Histological observation confirmed the induction of tumour in Group II animals and complete regression of tumour in Group III animals. This study highlights the potent antioxidant properties of TD which contribute to its therapeutic effect in AFB1-induced HCC in rats.

  8. Modification of nanocellulose by poly-lysine can inhibit the effect of fumonisin B1 on mouse liver cells.

    Science.gov (United States)

    Jebali, Ali; Yasini Ardakani, Seyed Ali; Shahdadi, Hossein; Balal Zadeh, Mohammad Hossein; Hekmatimoghaddam, Seyedhossein

    2015-02-01

    Fumonisin B1 is an important mycotoxin, mainly produced by Fusarium verticillioides. It has toxic effects on liver, brain, and kidney cells. The first aim of this study was to synthesize nanocellulose modified with poly-lysine (NMPL), and the second aim was to evaluate the adsorption of fumonisin B1 by NMPL. As third aim, the function of mouse liver cells was investigated after exposure to fumonisin B1, and fumonisin B1+ NMPL. In this study, NMPL was prepared using cross-linker, and then incubated with fumonisin B1 at controlled conditions. After incubation, the adsorption and release of fumonisin B1 were evaluated in each condition. Next, mouse liver cells were separately exposed to fumonisin B1, NMPL, and (fumonisin B1+NMPL). Then, the level of aniline aminotransferase (ALT) and aspartate aminotransferase (AST) was evaluated. It was found that both adsorption and release of fumonisin B1 were not affected by temperature and incubation time, but affected by pH and concentration of NMPL. Also, this study showed NMPL could adsorb fumonisin B1 in different foodstuffs. Importantly, although the levels of ALT and AST were increased when the cells were treated with fumonisin B1 alone, they were not affected when exposed to NMPL or (fumonisin B1+NMPL). The authors suggest that NMPL is a good adsorbent to remove and inhibit fumonisin B1. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Modelling approach to limit aflatoxin B1 contamination in dairy cattle compound feed

    NARCIS (Netherlands)

    Bouzembrak, Y.; Fels-Klerx, van der H.J.

    2016-01-01

    Feeding dairy cattle with safe compound feed helps farmers to ensure food safety. However, several ingredients often used in compound feed production can be contaminated with aflatoxin B1 (AFB1), which may result into milk contaminated with aflatoxin M1. Given the number of ingredients and their

  10. Calculating the best parameters B0 and B1 for the IRI profile from ionograms

    International Nuclear Information System (INIS)

    Huang Xueqin; Reinisch, B.W.

    1997-01-01

    This technical note describes the software tools developed at the University of Massachusetts Lowell for the calculation of the 'best' B0 and B1 for the IRI analytic function that describes the bottomside profile of the F2 layer. A step-by-step procedure is given starting with ionograms from Digisondes or any other ionosonde. 9 refs, 4 figs, 1 tab

  11. 26 CFR 1.691(b)-1 - Allowance of deductions and credit in respect to decedents.

    Science.gov (United States)

    2010-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Income in Respect of Decedents § 1.691(b)-1..., and taxes described in sections 162, 163, 164, and 212 for which the decedent (or a prior decedent... to pay such obligation, as a deduction by the person who by bequest, devise, or inheritance from the...

  12. 76 FR 6792 - Federal Management Regulation; FMR Bulletin PBS-2011-B1; Redesignations of Federal Buildings

    Science.gov (United States)

    2011-02-08

    ... Management Regulation; FMR Bulletin PBS-2011-B1; Redesignations of Federal Buildings AGENCY: Public Buildings... announces the redesignations of three Federal buildings. DATES: Expiration Date: This bulletin announcement expires June 30, 2011. The building redesignations remain in effect until canceled or superseded by...

  13. 17 CFR 270.10b-1 - Definition of regular broker or dealer.

    Science.gov (United States)

    2010-04-01

    ... COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.10b-1 Definition of regular broker or dealer. The term regular broker or dealer of an investment company shall mean: (a) One... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of regular broker...

  14. 17 CFR 270.5b-1 - Definition of “total assets.”

    Science.gov (United States)

    2010-04-01

    ... (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.5b-1 Definition of “total assets... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Definition of âtotal assets.â..., shall mean the gross assets of the company with respect to which the computation is made, taken as of...

  15. Loss of Cyp8b1 Improves Glucose Homeostasis by Increasing GLP-1

    NARCIS (Netherlands)

    Kaur, Achint; Patankar, Jay V.; de Haan, Willeke; Ruddle, Piers; Wijesekara, Nadeeja; Groen, Albert K.; Verchere, C. Bruce; Singaraja, Roshni R.; Hayden, Michael R.

    Besides their role in facilitating lipid absorption, bile acids are increasingly being recognized as signaling molecules that activate cell-signaling receptors. Targeted disruption of the sterol 12-hydroxylase gene (Cyp8b1) results in complete absence of cholic acid (CA) and its derivatives. Here we

  16. Screening of self-assembled monolayer for aflatoxin B1 detection using immune-capacitive sensor

    Directory of Open Access Journals (Sweden)

    Alvaro V. Gutierrez R

    2015-12-01

    Full Text Available A capacitive biosensor was used for detection of aflatoxin B1. Two different methods for cleaning gold electrodes were evaluated using cyclic voltammetry in the presence of ferricyanide as redox couple. The methods involve use of a sequence of cleaning steps avoiding the use of Piranha solution and plasma cleaner. Anti-aflatoxin B1 was immobilized on self-assembled monolayers (SAM. The immune-capacitive biosensor is able to detect aflatoxin B1 concentrations in a linear range of 3.2 × 10−12 M to 3.2 × 10−9 M when thiourea was used to form the SAM; 3.2 × 10−9 M to 3.2 × 10−7 M when thioctic acid was used. When the gold surface was isolated with tyramine-electropolymerization linear ranges of 3.2 × 10−13 M to 3.2 × 10−7 M and 3.2 × 10−9 M to 3.2 × 10−7 M where obtained, respectively. The results obtained show the difference in linear range, limit of detection, and limit of quantification when different self-assembled monolayers are used for aflatoxin B1 detection.

  17. 26 CFR 41.4482(b)-1 - Definition of taxable gross weight.

    Science.gov (United States)

    2010-04-01

    ... Motor Vehicles § 41.4482(b)-1 Definition of taxable gross weight. (a) Actual unloaded weight—(1) In... general. The taxable gross weight of a highway motor vehicle is the sum of the actual unloaded weight of the vehicle fully equipped for service, the actual unloaded weight of any semitrailers or trailers...

  18. Effect of the grain protein content locus Gpc-B1 on bread and pasta quality

    Science.gov (United States)

    Grain protein concentration (GPC) affects wheat nutritional value and several critical parameters for bread and pasta quality. A gene designated Gpc-B1, which is not functional in common and durum wheat cultivars, was recently identified in Triticum turgidum ssp. dicoccoides. The functional allele o...

  19. B1 but not B2 bradykinin receptor agonists promote DU145 prostate ...

    African Journals Online (AJOL)

    University of KwaZulu-Natal,. Private Bag X7, Congella 4013, Durban,. South Africa. Tel: +27 31 2604486. Fax: +27 31 2604338. Email: naidoot@ukzn.ac.za ..... ME, Leeb-Lundberg LM,Daaka Y. Requirement for di- rect cross-talk between b1 and b2 kinin receptors for the proliferation of androgen-insensitive prostate can-.

  20. Data of evolutionary structure change: 1AJ8B-1IOMA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1AJ8B-1IOMA 1AJ8 1IOM B A LAKGLEDVYIDQTNICYIDGKEGKLYYRGYSVEELAELS...>GLY CA 362 ASP CA 307 LYS CA 257 1IOM... A 1IOMA EKLARLVAEKHGHS ARG CA 182 1IOM A 1IOM... 2.0784668922424316 2 1IOM

  1. Spiral MR fingerprinting at 7T with simultaneous B1 estimation.

    Science.gov (United States)

    Buonincontri, Guido; Schulte, Rolf F; Cosottini, Mirco; Tosetti, Michela

    2017-09-01

    Magnetic resonance fingerprinting is an efficient, new approach for quantitative imaging with MR. We aimed to extend this technique to cases with B1+ inhomogeneities within the imaging volume. Previous approaches have used abrupt changes in flip angles to estimate the B1+ field simultaneously with T1 and T2, using a Cartesian approach in a small-animal scanner at 4.7T. Here, we evaluated whether a similar approach would be suitable for imaging human brains using spiral readouts with a 7T scanner. We found that our modified scheme could significantly reduce the adverse effects of B1+ inhomogeneities even in extreme cases, reducing both the bias and the variance in T2 estimations by an order of magnitude when compared to literature methods. Acquisitions used less than 1.5W/kg SAR and could be performed in 12s per slice. In conclusion, our approach can be used to perform quantitative imaging of the brain at 7T in a short time, simultaneously estimating the B1+ profile. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. 26 CFR 49.4262(b)-1 - Exclusion of certain travel.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Exclusion of certain travel. 49.4262(b)-1... Exclusion of certain travel. (a) In general. Under section 4262(b) taxable transportation does not include... computing tax on travel not excluded. (1) Where a payment is made for transportation which includes...

  3. 26 CFR 1.147(b)-1 - Bond maturity limitation-treatment of working capital.

    Science.gov (United States)

    2010-04-01

    ... and Local Bonds § 1.147(b)-1 Bond maturity limitation-treatment of working capital. Section 147(b) does not apply to proceeds of a private activity bond issue used to finance working capital... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Bond maturity limitation-treatment of working...

  4. 26 CFR 1.1311(b)-1 - Maintenance of an inconsistent position.

    Science.gov (United States)

    2010-04-01

    ..., or nonrecognition, as the case may be, in the year of the error, and (ii) such inconsistent position... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Maintenance of an inconsistent position. 1.1311....1311(b)-1 Maintenance of an inconsistent position. (a) In general. Under the circumstances stated in...

  5. A patient with a rare leukodystrophy related to lamin B1 duplication.

    LENUS (Irish Health Repository)

    Molloy, A

    2012-06-01

    The hereditary leukodystrophies are rare disorders caused by molecular abnormalities leading to destruction of or failure of development of central white matter. For almost 30 years there has been increasing recognition of later onset Autosomal Dominant Leukodystrophy (ADLD). We report the first genetically confirmed case of lamin B1 duplication causing ADLD from Ireland.

  6. Chromatin looping and epigenetic regulation at the maize b1 locus

    NARCIS (Netherlands)

    Louwers, M.L.D.

    2008-01-01

    In this thesis, the effect of epigenetic regulation on long-range chromatin looping is studied. As a model system we used two maize b1 epialleles involved in paramutation. Paramutation entails a trans-interaction between two alleles whereby one allele heritably changes the expression level of the

  7. 26 CFR 1.381(b)-1 - Operating rules applicable to carryovers in certain corporate acquisitions.

    Science.gov (United States)

    2010-04-01

    ... for the purpose of winding up its affairs, paying its debts, and distributing any remaining balance of... DISTRIBUTION OR TRANSFER PURSUANT TO § 1.381(b)-1(b)(2),” and must include: [INSERT NAME AND EMPLOYER IDENTIFICATION NUMBER (IF ANY) OF DISTRIBUTOR OR TRANSFEROR CORPORATION] AND [INSERT NAME AND EMPLOYER...

  8. Effect of fungicide on Fusarium verticillioidesmycelial morphology and fumonisin B1 production

    Directory of Open Access Journals (Sweden)

    Tatiana de Á. Miguel

    2015-03-01

    Full Text Available The effect of fludioxonil + metalaxyl-M on the mycelial morphology, sporulation and fumonisin B1 production by Fusarium verticillioides 103 F was evaluated. Scanning electron microscopy analysis showed that the fungicide caused inhibition of hyphal growth and defects on hyphae morphology such as cell wall disruption, withered hyphae, and excessive septation. In addition, extracellular material around the hyphae was rarely observed in the presence of fludioxonil + metalaxyl-M. While promoting the reduction of mycelial growth, the fungicide increased sporulation of F. verticillioides compared to the control, and the highest production occurred on the 14th day in the treatments and on the 10th day in the control cultures. Fumonisin B1production in the culture media containing the fungicide (treatment was detected from the 7th day incubation, whereas in cultures without fungicide (control it was detected on the 10th day. The highest fumonisin B1 production occurred on the 14th day, both for the control and for the treatment. Fludioxonil + metalaxyl - M can interfere in F. verticillioides mycelial morphology and sporulation and increase fumonisin B1 levels. These data indicate the importance of understanding the effects of fungicide to minimize the occurrence of toxigenic fungi and fumonisins.

  9. Inhibition of apoptic cell death induced by Pseudomonas syringae pv. Tabaci and mycotoxin fumonisin B1

    NARCIS (Netherlands)

    Iakimova, E.T.; Batchvorova, R.; Kapchina, V.; Popov, T.; Atanassov, A.; Woltering, E.J.

    2004-01-01

    The impact of programmed cell death (PCD) inhibitors on lesion formation and biochemical events in transgenic (ttr line) and non-transgenic (Nevrokop 1164) tobacco infected with Pseudomonas syringae pv. tabaci was tested. Programmed cell death in tomato cell culture was induced by Fumonisin B1 (FUM)

  10. Selection and application of strand displacement probes for a fumonisin B1 aptamer

    Science.gov (United States)

    Fumonisin B1 (FB1) is a toxin produced by Fusarium moniliforme, mainly on contaminated maize and maize products. In this study a solid surface chain displacement strategy was used to isolate oligonucleotide displacement probes for a FB1 aptamer. The probes were used as the basis for the development ...

  11. Effect of fumonisin B1 on rat hepatic P450 system

    NARCIS (Netherlands)

    Spotti, M.; Maas, R.F.M.; Nijs, C.M. de; Fink-Gremmels, J.

    2000-01-01

    The effects of the mycotoxin fumonisin B1 (FB1) on the hepatic cytochrome P450 system were investigated in male rats dosed daily by oral gavage with 3 mg FB1 per kg body weight for 9 consecutive days. FB1 treatment resulted in a reduced weight gain. At the same time, CYP2E activity was increased,

  12. Effect of fungicide on Fusarium verticillioides mycelial morphology and fumonisin B 1 production

    Science.gov (United States)

    Miguel, Tatiana de Á.; Bordini, Jaqueline G.; Saito, Gervásio H.; Andrade, Célia G.T. de J.; Ono, Mario A.; Hirooka, Elisa Y.; Vizoni, Édio; Ono, Elisabete Y.S.

    2015-01-01

    The effect of fludioxonil + metalaxyl-M on the mycelial morphology, sporulation and fumonisin B 1 production by Fusarium verticillioides 103 F was evaluated. Scanning electron microscopy analysis showed that the fungicide caused inhibition of hyphal growth and defects on hyphae morphology such as cell wall disruption, withered hyphae, and excessive septation. In addition, extracellular material around the hyphae was rarely observed in the presence of fludioxonil + metalaxyl-M. While promoting the reduction of mycelial growth, the fungicide increased sporulation of F. verticillioides compared to the control, and the highest production occurred on the 14 th day in the treatments and on the 10 th day in the control cultures. Fumonisin B 1 production in the culture media containing the fungicide (treatment) was detected from the 7 th day incubation, whereas in cultures without fungicide (control) it was detected on the 10 th day. The highest fumonisin B 1 production occurred on the 14 th day, both for the control and for the treatment. Fludioxonil + metalaxyl - M can interfere in F. verticillioides mycelial morphology and sporulation and increase fumonisin B 1 levels. These data indicate the importance of understanding the effects of fungicide to minimize the occurrence of toxigenic fungi and fumonisins. PMID:26221120

  13. A NEW CELL CLONE DERIVED FROM TRICHOPLUSIA NI TN5B1-4 CELLS

    Institute of Scientific and Technical Information of China (English)

    Jian-xiaoTian; Chang-youLi; Gui-lingZheng; Guo-xunLi; PingWang; Granados

    2004-01-01

    The characteristics of a cultured cell line do not always remain stable and may change upon continuous passage. Most continuous cell lines, even after cloning, possess several genotypes that are constantly changing. There are numerous selective and adaptive culture processes, in addition to genetic instability, that may improve phenotypic change in cell growth, virus susceptibility, gene expression, and production of virus. Similar detrimental effects of long term passaging of insect cells have also been reported for continuous cell lines, for example, Tn5B 1-4 cells, which are the most widely used for the baculovirus expression vector system (BEVS), provide superior production of recombinant proteins,however, this high productivity may be more evident in low passage cells. In this paper, we describe the isolation of a cell clone, Tn5B-40, from low passage Tn5B 1-4 cells. The growth characteristics,productions of virus, and high level of recombinant protein productions were determined. The results showed the susceptibility of both clone and Tn5B 1-4 cells to wild-type AcNPV was approximately the same rate with over 95% of infection; when the cloned cells were infected with recombinant baculoviruses expressing β-galactosidase and secreted alkaline phosphatase (SEAP), expression of the recombinant proteins from the cloned cells exceeded that from the parental Tn5B 1-4 cells.

  14. The frequency of presence of aflatoxin B1 in foodstuffs of vegetable origin

    Directory of Open Access Journals (Sweden)

    Gojković Vesna S.

    2017-01-01

    Full Text Available Cereals, nuts and spices are foods that are used in the daily human diet. According to FAO the average consumption of foods of vegetable origin in people’s diet is increasing. Due to inadequate conditions during storage of foods of vegetable origin, there is possibility of contamination by mold that produces mycotoxins. Since the intake of these products in organism has been increased, there is a risk of exposure to mycotoxins and their harmful effect on the consumers’ health. The aim of this study was to determine the presence of aflatoxin B1 in products of vegetable origin (cereals, nuts and spices. Aflatoxin B1 was determined by enzyme-imunochemical method (ELISA, using commercial kit. 38 samples were tested. In 25 analyzed samples, the content of aflatoxin B1 was higher than 1 μg/kg (1 μg/kg is limit of detection. Out of the total number of tested samples, in 18 samples the content of aflatoxin B1 was determined higher than the allowed amount for this product group by the current regulations (2 μg/kg for cereals, 2 μg/kg for nuts and 5 μg/kg for spices.

  15. Data of evolutionary structure change: 1CF5B-1RTCA [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1CF5B-1RTCA 1CF5 1RTC B A --------DVNFDLSTATAKTYTKFIEDFRATL-PFSHK...A 211 1RTC A 1RTCA...ain> 1RTC A 1RTCA SALYYYSTGGTQLPT...pdbChain> 1RTCA MRTRIRYNRRSA HHHHHH 1RTCA AYFFH-PDNQE

  16. Design and verification of the Risø-B1 airfoil family for wind turbines

    DEFF Research Database (Denmark)

    Fuglsang, P.; Bak, C.; Gaunaa, M.

    2004-01-01

    This paper presents the design and experimental verification of the Risø-B1 airfoil family for MW-size wind turbines with variable speed and pitch control. Seven airfoils were designed with thickness-to-chord ratios between 15% and 53% to cover the entire span of a wind turbine blade. The airfoils...

  17. CYP1B1 and myocilin gene mutations in Egyptian patients with ...

    African Journals Online (AJOL)

    Purpose: Primary congenital glaucoma (PCG) accounts for 26–29% of childhood blindness in Egypt. The identification of disease causing mutations has not been extensively investigated. We aimed to examine the frequency of CYP1B1 and MYOC mutations in PCG Egyptian patients, and study a possible ...

  18. Chemical and Toxicological Fate of Fumonisin B1 during Extrusion Processing of Corn Grits

    Science.gov (United States)

    Two batches of flaking corn grits were prepared by growing Fusarium verticillioides to contain low and high levels of fumonisin B1 (FB1), Batch-1 at 9.7 ppm and Batch-2 at 50 ppm FB1 as determined by HPLC. These two batches were extruded (Batch-1E; Batch-2E) or extruded with 10% w/w glucose supplem...

  19. The polymorphic integumentary mucin B.1 from Xenopus laevis contains the short consensus repeat.

    Science.gov (United States)

    Probst, J C; Hauser, F; Joba, W; Hoffmann, W

    1992-03-25

    The frog integumentary mucin B.1 (FIM-B.1), discovered by molecular cloning, contains a cysteine-rich C-terminal domain which is homologous with von Willebrand factor. With the help of the polymerase chain reaction, we now characterize a contiguous region 5' to the von Willebrand factor domain containing the short consensus repeat typical of many proteins from the complement system. Multiple transcripts have been cloned, which originate from a single animal and differ by a variable number of tandem repeats (rep-33 sequences). These different transcripts probably originate solely from two genes and are generated presumably by alternative splicing of an huge array of functional cassettes. This model is supported by analysis of genomic FIM-B.1 sequences from Xenopus laevis. Here, rep-33 sequences are arranged in an interrupted array of individual units. Additionally, results of Southern analysis revealed genetic polymorphism between different animals which is predicted to be within the tandem repeats. A first investigation of the predicted mucins with the help of a specific antibody against a synthetic peptide determined the molecular mass of FIM-B.1 to greater than 200 kDa. Here again, genetic polymorphism between different animals is detected.

  20. Molecular characterization of cytochrome P450 1B1 and effect of ...

    African Journals Online (AJOL)

    FMV

    2013-11-27

    Nov 27, 2013 ... control, and the results revealed that there was a large increase in CYP1B1 mRNA in liver (22.8), intestine (2.0) ... to exhibit carcinogenicity in experimental ani-mals and humans .... Each PCR reaction consisted of 10 µl of SYBR® Premix Ex TaqTM II .... mainly result from incomplete combustion of organic.

  1. Picking the Bone: The B-1 Bomber as a Platform for Innovation

    Science.gov (United States)

    2010-06-01

    August 1974 amidst the Watergate scandal . Vice President Gerald Ford took office and retained James Schlesinger as his secretary of defense...Jones assumed command in 1974 amidst the Nixon presidential scandal and the B-1A design testing dilemma. General Jones understood Schlesinger‘s

  2. 7 T body MRI: B1 shimming with simultaneous SAR reduction

    International Nuclear Information System (INIS)

    Bergen, Bob van den; Berg, Cornelis A T van den; Bartels, Lambertus W; Lagendijk, Jan J W

    2007-01-01

    The high frequency of the radiofrequency (RF) fields used in high field magnetic resonance imaging (MRI) results in electromagnetic field variations that can cause local regions to have a large specific absorption rate (SAR) and/or a low excitation. In this study, we evaluated the use of a B 1 shimming technique which can simultaneously improve the B + 1 homogeneity and reduce the SAR for whole body imaging at 7 T. Optimizations for four individual anatomies showed a reduction up to 74% of the peak SAR values with respect to a quadrature excitation and a simultaneous improvement of the B + 1 homogeneity varying between 39 and 75% for different optimization parameters. The average SAR was reduced with approximately 50% for all optimizations. The optimized phase and amplitude settings from an elliptical phantom model were applied to four realistic human anatomy models to evaluate whether a generic application without prior knowledge of the detailed human anatomy is possible. This resulted in an average improvement of the B + 1 homogeneity of 37% and an average reduction of the maximum and average SAR of 50 and 55%, respectively. It can be concluded that this generic method can be used as a simple method to improve the prospects of 7 T body imaging

  3. Data of evolutionary structure change: 1BT8B-1EN5B [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available e>KGLKK----GTTLQ >H ---- > ATOM ...bChain>B 1BT8B KNMAPKGSAPERPT cture>H ...DChain> LVLKG--DKLAV >EEEE -- EEEE...ence>LVWDPLGKRINT >EEEE EEEEe> AT...re> ATOM 2237 CA LYS B 80 12.251 15.102 18.409 1.00 11.94 C

  4. Chooz B1 start-up marked by total computer control

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    The start-up of Chooz B1, the first of EdF's latest generation 1450 MWe N4 reactors, marks the first use in a nuclear power plant of a fully computerised control room. Working in partnership with EdF, Sema Group designed and supplied the advanced command and control system for this plant. (Author)

  5. CYP264B1 from Sorangium cellulosum So ce56: a fascinating norisoprenoid and sesquiterpene hydroxylase.

    Science.gov (United States)

    Ly, Thuy T B; Khatri, Yogan; Zapp, Josef; Hutter, Michael C; Bernhardt, Rita

    2012-07-01

    Many terpenes and terpenoid compounds are known as bioactive substances with desirable fragrance and medicinal activities. Modification of such compounds to yield new derivatives with desired properties is particularly attractive. Cytochrome P450 monooxygenases are potential enzymes for these reactions due to their capability of performing different reactions on a variety of substrates. We report here the characterization of CYP264B1 from Sorangium cellulosum So ce56 as a novel sesquiterpene hydroxylase. CYP264B1 was able to convert various sesquiterpenes including nootkatone and norisoprenoids (α-ionone and β-ionone). Nootkatone, an important grapefruit aromatic sesquiterpenoid, was hydroxylated mainly at position C-13. The product has been shown to have the highest antiproliferative activity compared with other nootkatone derivatives. In addition, CYP264B1 was found to hydroxylate α- and β-ionone, important aroma compounds of floral scents, regioselectively at position C-3. The products, 3-hydroxy-β-ionone and 13-hydroxy-nootkatone, were confirmed by (1)H and (13)C NMR. The kinetics of the product formation was analyzed by high-performance liquid chromatography, and the K ( m ) and k (cat) values were calculated. The results of docking α-/β-ionone and nootkatone into a homology model of CYP264B1 revealed insights into the structural basis of these selective hydroxylations.

  6. 26 CFR 31.3302(b)-1 - Additional credit against tax.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Additional credit against tax. 31.3302(b)-1... credit against tax. (a) In general. In addition to the credit against the tax allowable for contributions... credit allowable against the tax for such year shall be the aggregate of the additional credits allowable...

  7. 26 CFR 1.514(b)-1 - Definition of debt-financed property.

    Science.gov (United States)

    2010-04-01

    ... unrelated business taxable income by operation of more than one provision of the Code. (3) Examples..., an exempt organization, owns two properties, a restaurant and an office building. In 1972, all the... of the restaurant, is rented to the public for purposes not described in section 514(b)(1) (A), (B...

  8. 26 CFR 1.50B-1 - Definitions of WIN expenses and WIN employees.

    Science.gov (United States)

    2010-04-01

    ... employee. (c) Trade or business expenses. The term “WIN expenses” includes only salaries and wages which... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Definitions of WIN expenses and WIN employees. 1... INCOME TAXES Rules for Computing Credit for Expenses of Work Incentive Programs § 1.50B-1 Definitions of...

  9. Activation route of the Schistosoma mansoni cathepsin B1 drug target

    Czech Academy of Sciences Publication Activity Database

    Jílková, Adéla; Horn, Martin; Řezáčová, Pavlína; Marešová, Lucie; Fajtová, Pavla; Brynda, Jiří; Vondrášek, Jiří; McKerrow, J. H.; Caffrey, C. R.; Mareš, Michael

    2015-01-01

    Roč. 22, č. 1 (2015), s. 39 ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] Institutional support: RVO:61388963 ; RVO:68378050 Keywords : Schistosoma mansoni * cathepsin B1 * sulfated polysaccharides Subject RIV: CE - Biochemistry

  10. Data of evolutionary structure change: 1A96B-1VDMG [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available 1A96B-1VDMG 1A96 1VDM B G -EKYIVTWDMLQIHARKLASRLMPSEQWKGIIAVSRGGL...VPGALLARELGIRHVDTVCISSYDHD--NQRELKVLKRAEGDGEG--FIVIDDLVDTGGTAVAIREMYP-----KAHFVTIFAKPAGRPLVDDYVVDIPQDTWIEQPWDMG...7 LEU CA 198 1VDM G 1VDMG.../n14> 1VDM G 1VDMG2 1VDM G 1VDMG

  11. B-1 Aircraft Main Hydraulic Pump Tests With MIL-H-87257 Hydraulic Fluid

    National Research Council Canada - National Science Library

    Sharma, Shashi

    1998-01-01

    In an effort to convert the B-1 aircraft from MIL-H-5606 to M1-H-87257, the Air Force sponsored a study conducted by Rockwell International from April 1991 through June 1992, under contract F34601-89-C-0401...

  12. The safety analysis of realization of the stabilization of beams B1/B2 supports project

    International Nuclear Information System (INIS)

    Aleshin, A.M.; Batij, V.G.; Glukhen'kij, V.N.; Kozoriz, V.I.; Klyuchnikov, A.A.; Kochnev, N.A.; Pavlovskij, L.I.; Rubezhanskij, Yu.I.; Sidorenko, N.V.; Stoyanov, A.I.; Shcherbin, V.N.

    2000-01-01

    The results of the analysis of radiation safety executed at preparing for realization of the stabilization of beams B1/B2 support are given. The comparison of results of the preliminary analysis of safety with the data received during realization of works is carried out

  13. O2(b1∑+g) relaxation in active medium of oxygen-iodine laser

    Science.gov (United States)

    Tolstov, G. I.; Zagidullin, M. V.; Khvatov, N. A.; Medvedkov, I. A.; Mikheyev, P. A.

    2018-04-01

    Rate constants for the removal of O2 b1∑+g by collisions with O2, N2, CO2 and H2O have been determined at temperature 297 K. O2(b1 ∑+g) was excited by pulses from a tunable dye laser, and the deactivation kinetics were followed by observing the temporal behavior of the b1∑+g - X3∑-g fluorescence. The removal rate constants for CO2, N2 and H2O were not strongly dependent on temperature, and could be represented by the expressions kCO2=(1.8+/-0.05)×10-16 kN2=(2.2 +/- 0.2)×10-15, and kH2O=(6.12+/-0.67)×10-12 cm3 molecule-1 s-1. Rate constant for O2(b1∑+ ) removal by O2(X), being orders of magnitude lower, represented by the fitted expression kO2=(3.67 +/- 0.06)×10-17 cm3 molecule-1 s-1. All of the rate constants measured at room temperature were found to be in good agreement with previously reported values.

  14. Genetic variation in the HSD17B1 gene and risk of prostate cancer.

    Directory of Open Access Journals (Sweden)

    Peter Kraft

    2005-11-01

    Full Text Available Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17beta-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Delta5-androsterone-3beta,17beta-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002 inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes

  15. Aflatoxin B1-producing Aspergillus in sun-dried medicinal plant materials

    Directory of Open Access Journals (Sweden)

    Chinaputi, A.

    2001-10-01

    Full Text Available Fifty sun-dried medicinal plants were obtained from fraditional drug stores in Songkhla Province, Thailand, and examined for Aspergillus and aflatoxin B1. 288 isolates of Aspergillus were obtaines by standard blotter plate and 25 species were identified. The most common species were A. niger with 99 isolates, A. Flavus 84 isolates, A. terreus 33 isolates, A. oryzae 25 isolates, A.nidulans (Emericella nidulans 10 isolates, A fumigatus 9 isolates and A. chevalieri (Eurotium chevalieri 8 isolates. The other species[A. alliaceus, A.auricomus, A. carbonarius, A. carneus, A. clavatus, A. fisheri(Sartorya fumigata, A. janus, A. melleus,A. ochraceus, A. phoencis, A. sparsus, A. terricola, A. thomii, A. versicolor, A. wentii and Aspergillus sp.1-3] each had 1-2 siolates. Ofthe 50 different plants examined,9 had no trace of Aspergillus, namely Cinnamomum zeylanicum, Illicium verum, Andrographis paniculate, Carthamus tinctorius, Eugenia caryophyllus, Elettaria cardomomum, Coriandrum sativum, Curcuma longa and Cassia garrettiana. The highest number of species(9 of Aspergillus was found on Rauvolfia serpentina.The ability of Aspergillus to form aflatoxin was determined in coconut milk agar by observing the intensity of blue fluorescence in agar surrounding the colonies under ultraviolet light and the yellow pigment under the colonies. The results showed the production of aflatoxin was limited to the one species, A. flavus, from which 84 isolates produced aflatoxin in 57 isolates(67.8%.Aflatoxin B1. production was confirmed by culturing fluorescencing isolates of A. flavus in coconut nilk broth and detecting by ELISA technique. Aflatoxin B1. showed increasing production after 2 days, stabilizing at 3-4 days, and the decreasing after 5-6 days. Aflatoxin B1. could not be detected from nonfluorescencing isolates.The morphological characteristics of the aflatoxin B1. -producing and non-producing strains of A. flavus were similar under light microscope and

  16. CYP1B1 and MYOC Mutations in Vietnamese Primary Congenital Glaucoma Patients.

    Science.gov (United States)

    Do, Tan; Shei, William; Chau, Pham Thi Minh; Trang, Doan Le; Yong, Victor H K; Ng, Xiao Yu; Chen, Yue Ming; Aung, Tin; Vithana, Eranga N

    2016-05-01

    Primary congenital glaucoma (PCG, OMIM 231300), the most common glaucoma in infancy, is caused by developmental defects in the anterior chamber angle. The 3 implicated genes are cytochrome P450 family I subfamily B polypeptide 1 (CYP1B1), latent transforming growth factor β-binding protein 2 (LTBP2), and myocilin (MYOC). In this study, we sought to determine CYP1B1 and MYOC sequence variations in a Vietnamese cohort of index cases with PCG and their families. Thirty Vietnamese subjects with PCG and 120 normal Vietnamese subjects were recruited. PCG was defined by the presence of at least 2 of the following clinical manifestations: increased corneal diameter (>10 mm at birth), corneal edema, Haab's striae, optic disc changes, and absence of other ocular or systemic diseases associated with childhood glaucoma. The coding exons, intron and exon boundaries, and untranslated regions of CYP1B1 and MYOC genes were PCR amplified and subjected to bidirectional sequencing in all subjects. We identified 2 homozygous and 3 heterozygous CYP1B1 sequence alterations in our study subjects. Among the 5 mutations identified, 2 (p.H279L and p.L283F) were novel mutations, whereas 3 (p.A121_S122insDRPAFA, p.L107V, and p.V320L) had been previously reported in PCG cases. None of these mutations was observed in any of the 120 controls. Haplotypes generated with 6 non-disease-causing intragenic single nucleotide polymorphisms detected in CYP1B1 indicated that the most common haplotype in Vietnamese population is similar to that found in Chinese and Japanese. The genotype-phenotype correlation showed no significant difference between mutation and no-mutation groups for quantitative clinical features (presenting intraocular pressure, corneal diameter, number of surgeries performed, the cup-to-disc ratio) as well as for qualitative factors (bilateral cases, phenotype severity, and the prognosis) (P>0.05). Five out of 30 families with PCG (16.7%) had disease attributable to CYP1B1 alterations

  17. The Arabidopsis thiamin-deficient mutant pale green1 lacks thiamin monophosphate phosphatase of the vitamin B1 biosynthesis pathway.

    Science.gov (United States)

    Hsieh, Wei-Yu; Liao, Jo-Chien; Wang, Hsin-Tzu; Hung, Tzu-Huan; Tseng, Ching-Chih; Chung, Tsui-Yun; Hsieh, Ming-Hsiun

    2017-07-01

    Thiamin diphosphate (TPP, vitamin B 1 ) is an essential coenzyme present in all organisms. Animals obtain TPP from their diets, but plants synthesize TPPde novo. We isolated and characterized an Arabidopsis pale green1 (pale1) mutant that contained higher concentrations of thiamin monophosphate (TMP) and less thiamin and TPP than the wild type. Supplementation with thiamin, but not the thiazole and pyrimidine precursors, rescued the mutant phenotype, indicating that the pale1 mutant is a thiamin-deficient mutant. Map-based cloning and whole-genome sequencing revealed that the pale1 mutant has a mutation in At5g32470 encoding a TMP phosphatase of the TPP biosynthesis pathway. We further confirmed that the mutation of At5g32470 is responsible for the mutant phenotypes by complementing the pale1 mutant with constructs overexpressing full-length At5g32470. Most plant TPP biosynthetic enzymes are located in the chloroplasts and cytosol, but At5g32470-GFP localized to the mitochondrion of the root, hypocotyl, mesophyll and guard cells of the 35S:At5g32470-GFP complemented plants. The subcellular localization of a functional TMP phosphatase suggests that the complete vitamin B1 biosynthesis pathway may involve the chloroplasts, mitochondria and cytosol in plants. Analysis of PALE1 promoter-uidA activity revealed that PALE1 is mainly expressed in vascular tissues of Arabidopsis seedlings. Quantitative RT-PCR analysis of TPP biosynthesis genes and genes encoding the TPP-dependent enzymes pyruvate dehydrogenase, α-ketoglutarate dehydrogenase and transketolase revealed that the transcript levels of these genes were upregulated in the pale1 mutant. These results suggest that endogenous levels of TPP may affect the expression of genes involved in TPP biosynthesis and TPP-dependent enzymes. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  18. ATP8B1 requires an accessory protein for endoplasmic reticulum exit and plasma membrane lipid flippase activity

    NARCIS (Netherlands)

    Paulusma, Coen C.; Folmer, Dineke E.; Ho-Mok, Kam S.; de Waart, D. Rudi; Hilarius, Petra M.; Verhoeven, Arthur J.; Oude Elferink, Ronald P. J.

    2008-01-01

    Mutations in ATP8B1 cause progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1. Previously, we have shown in mice that Atp8b1 deficiency leads to enhanced biliary excretion of phosphatidylserine, and we hypothesized that ATP8B1 is a flippase for

  19. 17 CFR 270.30b1-1 - Semi-annual report for registered management investment companies.

    Science.gov (United States)

    2010-04-01

    ... registered management investment companies. 270.30b1-1 Section 270.30b1-1 Commodity and Securities Exchanges....30b1-1 Semi-annual report for registered management investment companies. Every registered management... management investment company that has filed a registration statement with the Commission registering its...

  20. 17 CFR 270.12b-1 - Distribution of shares by registered open-end management investment company.

    Science.gov (United States)

    2010-04-01

    ... registered open-end management investment company. 270.12b-1 Section 270.12b-1 Commodity and Securities... 1940 § 270.12b-1 Distribution of shares by registered open-end management investment company. (a)(1... the printing and mailing of sales literature; (b) A registered, open-end management investment company...

  1. Effect of vitamin B1 and mixtures of B1 with other vitamins on cytostatica efficiency under irradiation. A study in vitro

    International Nuclear Information System (INIS)

    Heinrich, E.; Getoff, N.

    2002-01-01

    Complete text of publication follows. In the last decades the research of malignant tumors (oncology) became a complex interdisciplinary branch of the modern sciences. In addition to other disciplines the radiation chemistry and radiation biology, applied in this respect, led to new and deeper understanding and knowledge in the radiation therapy of cancer. Following this line and by a combined use of both methods, studies in vitro for testing cytostatica activity and pulse radiolysis for characterisation of the corresponding transients, it was possible to gain a deeper and extensive understanding of complex reaction mechanisms. In addition to valuable biological data we have established that the cytostatica efficiency, e.g. of mitomycin C (MMC) can be very strongly increased in the presence of the vitamins C, E and β-carotene. As an essential step in this respect a cascade electron transfer with the sequence: vit. C → vit. E· + /vit. E → β-car. · + /β-car. → MMC/MMC· - was established. In the present work the ability of vitamin B1 (thiamine) to act under given conditions as cytostaticum or/and as radiation protecting agent will be reported. Extensive investigations in vitro (E. coli bacteria AB 1157 were used as a model) in different media showed that with a combination of vitamin B1 with sanazole (AK-2123) a synergistic effect occurs, which results in a very strong cytostatica enhancement. The presence of vitamin C in the system strongly contributes in this respect. The influence on the sanazole efficiency by other vitamins (E and β-carotene) added individually or in mixture will also be reported. The obtained results are of importance for the radiation therapy of cancer patients. The paper also demonstrates the significant role of radiation chemistry in radiation biology and medicine

  2. Nematode and arthropod genomes provide new insights into the evolution of class 2 B1 GPCRs.

    Science.gov (United States)

    Cardoso, João C R; Félix, Rute C; Power, Deborah M

    2014-01-01

    Nematodes and arthropods are the most speciose animal groups and possess Class 2 B1 G-protein coupled receptors (GPCRs). Existing models of invertebrate Class 2 B1 GPCR evolution are mainly centered on Caenorhabditis elegans and Drosophila melanogaster and a few other nematode and arthropod representatives. The present study reevaluates the evolution of metazoan Class 2 B1 GPCRs and orthologues by exploring the receptors in several nematode and arthropod genomes and comparing them to the human receptors. Three novel receptor phylogenetic clusters were identified and designated cluster A, cluster B and PDF-R-related cluster. Clusters A and B were identified in several nematode and arthropod genomes but were absent from D. melanogaster and Culicidae genomes, whereas the majority of the members of the PDF-R-related cluster were from nematodes. Cluster A receptors were nematode and arthropod-specific but shared a conserved gene environment with human receptor loci. Cluster B members were orthologous to human GCGR, PTHR and Secretin members with which they probably shared a common origin. PDF-R and PDF-R related clusters were present in representatives of both nematodes and arthropods. The results of comparative analysis of GPCR evolution and diversity in protostomes confirm previous notions that C. elegans and D. melanogaster genomes are not good representatives of nematode and arthropod phyla. We hypothesize that at least four ancestral Class 2 B1 genes emerged early in the metazoan radiation, which after the protostome-deuterostome split underwent distinct selective pressures that resulted in duplication and deletion events that originated the current Class 2 B1 GPCRs in nematode and arthropod genomes.

  3. Theoretical study of B3-to-B1 phase transition in ZnS

    International Nuclear Information System (INIS)

    Li, Qiang; Zhang, Rui; Lv, Tianquan; Cao, Qilong

    2016-01-01

    The pressure-induced phase transformation from B3 to B1 structures in ZnS using first-principle projector-augmented wave method is studied. To understand the nature and driving force behind the transition, the interesting properties in both phases, including enthalpy, phonon dispersion curves and elastic constants, are systematically investigated. The results show that the calculated transition pressure is within the range of 16.33 GPa to 19.04 GPa, which is in good agreement with the available experimental and theoretical data. The transition process can be viewed as the appearance and disappearance of very slight lattice distortion accompanied by the movement of Zn and S atoms along the [111] crystallographic axis. The physical driving force of the B3–B1 phase transition is confirmed to be a coupling effect between the mechanical instability of B3 phase under pressure and the softening acoustic phonon mode resulting from the pressure-induced lattice deformation. For B1 phase, it is further predicted that a new phase transition takes place at about 59.9 GPa. - Highlights: • The phase transformation from B3 to B1 structures in ZnS is studied using first-principle method. • The predicted transition pressure is within the range of 16.33 to 19.04 GPa. • The transition process can be viewed as the appearance and disappearance of very slight lattice distortion. • Physical driving force of the transition is a coupling effect between the mechanical instability and softening phonon. • For B1 phase, it is further predicted that a new phase transition takes place at about 59.9 GPa.

  4. Role of Phosphate Transport System Component PstB1 in Phosphate Internalization by Nostoc punctiforme.

    Science.gov (United States)

    Hudek, L; Premachandra, D; Webster, W A J; Bräu, L

    2016-11-01

    In bacteria, limited phosphate availability promotes the synthesis of active uptake systems, such as the Pst phosphate transport system. To understand the mechanisms that facilitate phosphate accumulation in the cyanobacterium Nostoc punctiforme, phosphate transport systems were identified, revealing a redundancy of Pst phosphate uptake systems that exists across three distinct operons. Four separate PstB system components were identified. pstB1 was determined to be a suitable target for creating phenotypic mutations that could result in the accumulation of excessive levels of phosphate through its overexpression or in a reduction of the capacity to accumulate phosphate through its deletion. Using quantitative real-time PCR (qPCR), it was determined that pstB1 mRNA levels increased significantly over 64 h in cells cultured in 0 mM added phosphate and decreased significantly in cells exposed to high (12.8 mM) phosphate concentrations compared to the level in cells cultured under normal (0.8 mM) conditions. Possible compensation for the loss of PstB1 was observed when pstB2, pstB3, and pstB4 mRNA levels increased, particularly in cells starved of phosphate. The overexpression of pstB1 increased phosphate uptake by N. punctiforme and was shown to functionally complement the loss of PstB in E. coli PstB knockout (PstB - ) mutants. The knockout of pstB1 in N. punctiforme did not have a significant effect on cellular phosphate accumulation or growth for the most part, which is attributed to the compensation for the loss of PstB1 by alterations in the pstB2, pstB3, and pstB4 mRNA levels. This study provides novel in vivo evidence that PstB1 plays a functional role in phosphate uptake in N. punctiforme IMPORTANCE: Cyanobacteria have been evolving over 3.5 billion years and have become highly adept at growing under limiting nutrient levels. Phosphate is crucial for the survival and prosperity of all organisms. In bacteria, limited phosphate availability promotes the

  5. Tumoral vitamin D synthesis by CYP27B1 1-alpha-hydroxylase delays mammary tumor progression in the PyMT-MMTV mouse model and its action involves NF-kappaB modulation

    Science.gov (United States)

    Biologically-active vitamin D (1,25(OH)2D) is synthetized from inactive prohormone 25(OH)D by the enzyme CYP27B1 1-a-hydroxylase in kidney and several extra-renal tissues including breast. While the development of breast cancer has been linked to inadequate vitamin D status, the importance of bioac...

  6. B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS

    Science.gov (United States)

    Pedersen, Gabriel K.; Àdori, Monika; Khoenkhoen, Sharesta; Dosenovic, Pia; Beutler, Bruce; Karlsson Hedestam, Gunilla B.

    2014-01-01

    B-1 cells mediate early protection against infection by responding to T cell-independent (TI) antigens found on the surface of various pathogens. Mice with impaired expression of the atypical IκB protein IκBNS have markedly reduced frequencies of B-1 cells. We used a mouse strain with dysfunctional IκBNS derived from an N-ethyl-N-nitrosourea (ENU) screen, named bumble, to investigate the point in the development of B-1 cells where IκBNS is required. The presence of wild-type (wt) peritoneal cells in mixed wt/bumble chimeras did not rescue the development of bumble B-1 cells, but wt peritoneal cells transferred to bumble mice restored natural IgM levels and response to TI antigens. The bumble and wt mice displayed similar levels of fetal liver B-1 progenitors and splenic neonatal transitional B (TrB) cells, both of which were previously shown to give rise to B-1 cells. Interestingly, we found that a subset of wt neonatal TrB cells expressed common B-1a markers (TrB-1a) and that this cell population was absent in the bumble neonatal spleen. Sorted TrB-1a (CD93+IgM+CD5+) cells exclusively generated B-1a cells when adoptively transferred, whereas sorted CD93+IgM+CD5− cells gave rise to B-2 cells and, to a lesser extent, B-1b and B-1a cells. This study identifies a phenotypically distinct splenic population of TrB-1a cells and establishes that the development of B-1a cells is blocked before this stage in the absence of IκBNS. PMID:25228759

  7. Fate of Fumonisin B1 in Naturally Contaminated Corn during Ethanol Fermentation

    Science.gov (United States)

    Bothast, R. J.; Bennett, G. A.; Vancauwenberge, J. E.; Richard, J. L.

    1992-01-01

    Two lots of corn naturally contaminated with fumonisin B1 (15 and 36 ppm) and a control lot (no fumonisin B1 detected) were used as substrates for ethanol production in replicate 8.5-liter yeast fermentations. Ethanol yields were 8.8% for both the control and low-fumonisin corn, while the high-fumonisin corn contained less starch and produced 7.2% ethanol. Little degradation of fumonisin occurred during fermentation, and most was recovered in the distillers' grains, thin stillage, and distillers' solubles fractions. No toxin was detected in the distilled alcohol or centrifuge solids. Ethanol fermentation of fumonisin-contaminated corn coupled with effective detoxification of distillers' grains and aqueous stillage is suggested as a practical process strategy for salvaging contaminated corn. PMID:16348623

  8. ESTIMATION OF AFLATOXIN B1 IN FEED INGREDIENTS AND COMPOUND POULTRY FEEDS

    Directory of Open Access Journals (Sweden)

    Bashir Mahmood Bhatti, Tanzeela Talat and Rozina Sardar

    2001-02-01

    Full Text Available A total of 3230 samples of feed ingredients of vegetable and animal origin and commercially available compound poultry feed received over a period of 5 years at Feed Testing Laboratory of the Institute were tested for Aflatoxin B1 contents (ppb . In all feed ingredients and compound feed stuffs, minimum level of aflatoxin B1 was 13 ppb and maximum level was found to be 78 ppb. No correlation of aflatoxin levels with month of collection of the year which are subject to variation in temperature and humidity could be detected. Mean values of aflatoxin concentration in feed stuffs such as rice, rice polish, wheat bran, wheat bread, maize, fish meal, blood meal, bone meal, guar meal, corn gluten 30%, corn gluten 60%, sun flower meal, soyabean meal and cotton seed meal were found to be higher than safe level of 20 ppb recommended by FDA.

  9. The influence of alloying elements in aluminium on the grain refinement with ALTI5B1

    Directory of Open Access Journals (Sweden)

    Naglič I.

    2009-07-01

    Full Text Available This work deals with the influence of alloying elements in aluminium on the grain refinement with various additions of AlTi5B1. Grain-refinement tests were made at a cooling rate of 15 °C/s. The results revealed that in both aluminium and an Al-Fe alloy the grain size decreases with increasing additions of the AlTi5B1 grain refiner. We found that for the same boron content the grain size was smaller in the case of the Al-Fe alloy. The difference in the grain sizes for the same content of boron was approximately 15 μm; this is considerably smaller than the difference between the grain sizes in samples with the same difference of growth-restricting factor made at slower cooling rates.

  10. 291-B-1 stack monitoring and sampling system annual system assessment report

    International Nuclear Information System (INIS)

    Ridge, T.M.

    1994-01-01

    The B Plant 291-B-1 main stack exhausts gaseous effluents to the atmosphere from the 221-B Building canyon and cells, the No. 1 Vessel Ventilation System (VVS1), the 212-B Cask Station cell ventilation system, and, to a limited capacity, the 224-B Building. VVS1 collects offgases from various process tanks in 221-B Building, while the 224-B system maintains a negative pressure in out-of-service, sealed process tanks. B Plant Administration Manual, WHC-CM-7-5, Section 5.30 requires an annual system assessment to evaluate and report the present condition of the sampling and monitoring system associated with Stack 291-B-1 (System Number B977A) at B Plant. The system is functional and performing satisfactorily

  11. Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.

    Science.gov (United States)

    Yee, S W; Giacomini, M M; Hsueh, C-H; Weitz, D; Liang, X; Goswami, S; Kinchen, J M; Coelho, A; Zur, A A; Mertsch, K; Brian, W; Kroetz, D L; Giacomini, K M

    2016-11-01

    Transporter-mediated drug-drug interactions (DDIs) are a major cause of drug toxicities. Using published genome-wide association studies (GWAS) of the human metabolome, we identified 20 metabolites associated with genetic variants in organic anion transporter, OATP1B1 (P acids and fatty acid dicarboxylates were among the metabolites discovered using both GWAS and CSA administration. In vitro studies confirmed tetradecanedioate (TDA) and hexadecanedioate (HDA) were novel substrates of OATP1B1 as well as OAT1 and OAT3. This study highlights the use of multiple datasets for the discovery of endogenous metabolites that represent potential in vivo biomarkers for transporter-mediated DDIs. Future studies are needed to determine whether these metabolites can serve as qualified biomarkers for organic anion transporters. Quantitative relationships between metabolite levels and modulation of transporters should be established. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  12. Receptor oligomerization in family B1 of G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

    2012-01-01

    , the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this......, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades...

  13. [Biofilm Formation by the Nonflagellated flhB1 Mutant of Azospirillum brasilense Sp245].

    Science.gov (United States)

    Shelud'ko, A V; Filip'echeva, Yu A; Shumiliva, E M; Khlebtsov, B N; Burov, A M; Petrova, L P; Katsy, E I

    2015-01-01

    Azospirillum brasilense Sp245 with mixed flagellation are able to form biofilms on various surfaces. A nonflagellated mutant of this strain with inactivated chromosomal copy of the flhB gene (flhB1) was shown to exhibit specific traits at the later stages of biofilm formation on a hydrophilic (glass) surface. Mature biofilms of the flhB1::Omegon-Km mutant Sp245.1063 were considerably thinner than those of the parent strain Sp245. The biofilms of the mutant were more susceptible to the forces of hydrodynamic shear. A. brasilense Sp245 cells in biofilms were not found to possess lateral flagella. Cells with polar flagella were, however, revealed by atomic force microscopy of mature native biofilms of strain Sp245. Preservation of a polar flagellum (probably nonmotile) on the cells of A. brasilense Sp245 may enhance the biofilm stability.

  14. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    OpenAIRE

    Adriana Frizzarin; Thiago Pereira Motta; Thamires Martins; Livia Castelani; Heloisa Solda de Azevedo; Cláudia Rodrigues Pozzi

    2012-01-01

    Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, preg...

  15. Effect of gamma radiation on the inactivation of aflatoxin B1 in food and feed crops

    International Nuclear Information System (INIS)

    Ghanem, I.; Orfi, M.; Shamma, M.

    2007-08-01

    Samples of food crops (peanut, peeled pistachio, unpeeled pistachio, rice, and corn) and feed (barley, bran, corn) were sterilized then inoculated with 10 6 of spore suspension of an isolate of Aspergillus flavus fungus known to produce aflatoxin B1 . Food and feed samples were irradiated with gamma radiation at the doses 4, 6, and 10 kGy. Results indicated that degradation of Aflatoxin B1 was positively correlated with the increase in the applied dose of gamma ray for each tested sample. For example, at a dose of 4 KGy. Percentages of aflatoxin B1 degradation were 8.4, 9.7, 16.6 and 23.5, and 43.97% for peanuts, peeled pistachios, unpeeled pistachios, corn and rice, consecutively . Whereas, at a dose of 10 KGy percentages of aflatoxin degradation reached highest values at 58.6, 68.8, 84.6, 81.1 and 87.8% for peanuts, peeled pistachios, unpeeled pistachios, corn and rice, consecutively In feed samples percentages of aflatoxin degradation were 45, 66, and 90% in barley, 47, 75, and 86% in bran, and 31, 72, and 84% in corn for the doses of 4, 6, and 10 KGy, consecutively. Aflatoxin degradation in food samples correlated negatively with oil content in irradiated samples. Thus, in peanuts, which contained the highest oil content, percentage of aflatoxin degradation at 10 KGy was not more than 56.6%, whereas, the corresponding value in corn, which contained the highest oil content, reached as high as 80%. The above results indicate the possibility of using gamma irradiation as a means of degradation of aflatoxin B1 in food and feed crops to lower than the maximum allowed levels using a maximum dose of radiation of 10 KGy which represents the permitted dose of radiation for such type of crops.(author)

  16. Effect of gamma radiation on the inactivation of aflatoxin B1 in food and feed crops

    International Nuclear Information System (INIS)

    Ghanem, I.; Orfi, M.; Shamma, M.

    2008-01-01

    Samples of food crops (peanut, peeled pistachio, unpeeled pistachio, rice, and corn) and feed (barley, bran, corn) were autoclave-sterilized, and inoculated with 106 of spore suspension of an isolate of Aspergillus flavus fungus known to produce aflatoxin B1. Food and feed samples were irradiated with gamma radiation at the doses 4, 6, and 10 kGy. Results indicated that degradation of Aflatoxin B1 was positively correlated with the increase in the applied dose of gamma ray for each tested sample. At a dose of 4 KGy percentages of aflatoxin B1 degradation were 8.4, 9.7, 16.6 and 23.5, and 43.97% for peanuts, peeled pistachios, unpeeled pistachios, corn and rice, respectively. Whereas, at a dose of 10 KGy percentages of aflatoxin degradation reached highest values at 58.6, 68.8, 84.6, 81.1 and 87.8% for peanuts, peeled pistachios, unpeeled pistachios, corn and rice, respectively. In feed samples percentages of aflatoxin degradation were 45, 66, and 90% in barley, 47, 75 and 86% in bran and 31, 72 and 84% in corn for the doses of 4, 6 and 10 KGy, respectively, Aflatoxin degradation in food samples correlated negatively with oil content in irradiated samples. Thus, in peanuts, which contained the highest oil content, percentage of aflatoxin degradation at 10 KGy was not more than 56.6% whereas, the corresponding value in corn, which contained the highest oil content, reached as high as 80%. The above results indicate the possibility of using gamma radiation as a means of degradation of aflatoxin B1 in food and feed crops to levels lower than the maximum allowed levels.(author)

  17. Exercices de grammaire B1 du cadre européen

    CERN Document Server

    Beaulieu, Christian

    2007-01-01

    Ce cahier d'exercices s'adresse à des apprenants en français. Il présente des activités d'entraînement correspondant au niveau B1 du Cadre Européen commun de référence pour les langues. Ce cahier peut être utilisé en classe ou en autonomie.

  18. Effect of gamma radiation on the inactivation of aflatoxin B1 in food and feed crops

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, I; Orfi, M; Shamma, M [Atomic Energy Commission, Damascus (Syrian Arab Republic), Dept. of Molecular Biology and Biotechnology

    2008-09-15

    Samples of food crops (peanut, peeled pistachio, unpeeled pistachio, rice, and corn) and feed (barley, bran, corn) were autoclave-sterilized, and inoculated with 106 of spore suspension of an isolate of Aspergillus flavus fungus known to produce aflatoxin B1. Food and feed samples were irradiated with gamma radiation at the doses 4, 6, and 10 kGy. Results indicated that degradation of Aflatoxin B1 was positively correlated with the increase in the applied dose of gamma ray for each tested sample. At a dose of 4 KGy percentages of aflatoxin B1 degradation were 8.4, 9.7, 16.6 and 23.5, and 43.97% for peanuts, peeled pistachios, unpeeled pistachios, corn and rice, respectively. Whereas, at a dose of 10 KGy percentages of aflatoxin degradation reached highest values at 58.6, 68.8, 84.6, 81.1 and 87.8% for peanuts, peeled pistachios, unpeeled pistachios, corn and rice, respectively. In feed samples percentages of aflatoxin degradation were 45, 66, and 90% in barley, 47, 75 and 86% in bran and 31, 72 and 84% in corn for the doses of 4, 6 and 10 KGy, respectively, Aflatoxin degradation in food samples correlated negatively with oil content in irradiated samples. Thus, in peanuts, which contained the highest oil content, percentage of aflatoxin degradation at 10 KGy was not more than 56.6% whereas, the corresponding value in corn, which contained the highest oil content, reached as high as 80%. The above results indicate the possibility of using gamma radiation as a means of degradation of aflatoxin B1 in food and feed crops to levels lower than the maximum allowed levels.(author)

  19. Effect of gamma radiation on the inactivation of aflatoxin B1 in food and feed crops

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, I; Orfi, M; Shamma, M [Atomic Energy Commission, Damascus (Syrian Arab Republic), Dept. of Molecular Biology and Biotechnology

    2007-08-15

    Samples of food crops (peanut, peeled pistachio, unpeeled pistachio, rice, and corn) and feed (barley, bran, corn) were sterilized then inoculated with 10{sup 6} of spore suspension of an isolate of Aspergillus flavus fungus known to produce aflatoxin B1 . Food and feed samples were irradiated with gamma radiation at the doses 4, 6, and 10 kGy. Results indicated that degradation of Aflatoxin B1 was positively correlated with the increase in the applied dose of gamma ray for each tested sample. For example, at a dose of 4 KGy. Percentages of aflatoxin B1 degradation were 8.4, 9.7, 16.6 and 23.5, and 43.97% for peanuts, peeled pistachios, unpeeled pistachios, corn and rice, consecutively . Whereas, at a dose of 10 KGy percentages of aflatoxin degradation reached highest values at 58.6, 68.8, 84.6, 81.1 and 87.8% for peanuts, peeled pistachios, unpeeled pistachios, corn and rice, consecutively In feed samples percentages of aflatoxin degradation were 45, 66, and 90% in barley, 47, 75, and 86% in bran, and 31, 72, and 84% in corn for the doses of 4, 6, and 10 KGy, consecutively. Aflatoxin degradation in food samples correlated negatively with oil content in irradiated samples. Thus, in peanuts, which contained the highest oil content, percentage of aflatoxin degradation at 10 KGy was not more than 56.6%, whereas, the corresponding value in corn, which contained the highest oil content, reached as high as 80%. The above results indicate the possibility of using gamma irradiation as a means of degradation of aflatoxin B1 in food and feed crops to lower than the maximum allowed levels using a maximum dose of radiation of 10 KGy which represents the permitted dose of radiation for such type of crops.(author)

  20. Fluorescent sensor systems based on nanostructured polymeric membranes for selective recognition of Aflatoxin B1.

    Science.gov (United States)

    Sergeyeva, Tetyana; Yarynka, Daria; Piletska, Elena; Lynnik, Rostyslav; Zaporozhets, Olga; Brovko, Oleksandr; Piletsky, Sergey; El'skaya, Anna

    2017-12-01

    Nanostructured polymeric membranes for selective recognition of aflatoxin B1 were synthesized in situ and used as highly sensitive recognition elements in the developed fluorescent sensor. Artificial binding sites capable of selective recognition of aflatoxin B1 were formed in the structure of the polymeric membranes using the method of molecular imprinting. A composition of molecularly imprinted polymer (MIP) membranes was optimized using the method of computational modeling. The MIP membranes were synthesized using the non-toxic close structural analogue of aflatoxin B1, ethyl-2-oxocyclopentanecarboxylate as a dummy template. The MIP membranes with the optimized composition demonstrated extremely high selectivity towards aflatoxin B1 (AFB1). Negligible binding of close structural analogues of AFB1 - aflatoxins B2 (AFB2), aflatoxin G2 (AFG2), and ochratoxin A (OTA) was demonstrated. Binding of AFB1 by the MIP membranes was investigated as a function of both type and concentration of the functional monomer in the initial monomer composition used for the membranes' synthesis, as well as sample composition. The conditions of the solid-phase extraction of the mycotoxin using the MIP membrane as a stationary phase (pH, ionic strength, buffer concentration, volume of the solution, ratio between water and organic solvent, filtration rate) were optimized. The fluorescent sensor system based on the optimized MIP membranes provided a possibility of AFB1 detection within the range 14-500ngmL -1 demonstrating detection limit (3Ϭ) of 14ngmL -1 . The developed technique was successfully applied for the analysis of model solutions and waste waters from bread-making plants. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Incidence of Fusarium spp. and Levels of Fumonisin B1 in Maize in Western Kenya

    Science.gov (United States)

    Kedera, C. J.; Plattner, R. D.; Desjardins, A. E.

    1999-01-01

    Maize kernel samples were collected in 1996 from smallholder farm storages in the districts of Bomet, Bungoma, Kakamega, Kericho, Kisii, Nandi, Siaya, Trans Nzoia, and Vihiga in the tropical highlands of western Kenya. Two-thirds of the samples were good-quality maize, and one-third were poor-quality maize with a high incidence of visibly diseased kernels. One hundred fifty-three maize samples were assessed for Fusarium infection by culturing kernels on a selective medium. The isolates obtained were identified to the species level based on morphology and on formation of the sexual stage in Gibberella fujikuroi mating population tests. Fusarium moniliforme (G. fujikuroi mating population A) was isolated most frequently, but F. subglutinans (G. fujikuroi mating population E), F. graminearum, F. oxysporum, F. solani, and other Fusarium species were also isolated. The high incidence of kernel infection with the fumonisin-producing species F. moniliforme indicated a potential for fumonisin contamination of Kenyan maize. However, analysis of 197 maize kernel samples by high-performance liquid chromatography found little fumonisin B1 in most of the samples. Forty-seven percent of the samples contained fumonisin B1 at levels above the detection limit (100 ng/g), but only 5% were above 1,000 ng/g, a proposed level of concern for human consumption. The four most-contaminated samples, with fumonisin B1 levels ranging from 3,600 to 11,600 ng/g, were from poor-quality maize collected in the Kisii district. Many samples with a high incidence of visibly diseased kernels contained little or no fumonisin B1, despite the presence of F. moniliforme. This result may be attributable to the inability of F. moniliforme isolates present in Kenyan maize to produce fumonisins, to the presence of other ear rot fungi, and/or to environmental conditions unfavorable for fumonisin production. PMID:9872757

  2. A Condition Based Maintenance Approach to Forecasting B-1 Aircraft Parts

    Science.gov (United States)

    2017-03-23

    Air Force Institute of Technology AFIT Scholar Theses and Dissertations 3-23-2017 A Condition Based Maintenance Approach to Forecasting B-1 Aircraft...component’s life history where reliability forecasts could be stipulated based on a component’s current condition . One of the major issues their report noted...Engine Condition Monitoring System Specification. Contract Number DOT-CG-80513-A. Grand Prairie, TX. Air Force Materiel Command. (2011) Requirements For

  3. Assessment of workers’ exposure to Aflatoxin B1 in a Portuguese waste industry

    OpenAIRE

    Viegas, Susana; Veiga, Luísa; Figueredo, Paula; Almeida, Ana; Carolino, Elisabete; Viegas, Carla

    2015-01-01

    Aflatoxin B1 (AFB1) is considered by different International Agencies as a genotoxic and potent hepatocarcinogen. However, despite the fact that the fungi producing this compound are detected in some work environments, AFB1 is rarely monitored in occupational settings. The aim of the present investigation was to assess exposure to AFB1 of workers from one Portuguese waste company located in the outskirt of Lisbon. Occupational exposure assessment to AFB1 was done with a biomarker of internal ...

  4. Reactive scattering of B+(1S/sub g/) by molecular deuterium

    International Nuclear Information System (INIS)

    Sondergaard, N.A.; Sauers, I.; Kaufman, J.J.; Koski, W.S.

    1979-01-01

    The angular and energy distribution of ionic products from the reaction of B + ( 1 S/sub g/) with D 2 was studied over a projectile energy range of 10 to 50 eV in the laboratory system. The product states as determined from the limiting values of the translational exoergicity were BD + ( 2 Σ + ) and BD + ( 2 π). The experimental measurements and theoretical considerations suggest that both of these reactions are proceeding through a persistent complex

  5. Targeting Sulfotransferase (SULT) 2B1b as a regulator of Cholesterol Metabolism in Prostate Cancer

    Science.gov (United States)

    2016-10-01

    associated with de novo androgen synthesis will be addressed based on the hypothesis that SULT2B1b promotes PCa proliferation by impacting the...evaluation of sulfonation activity on other sterols using in vitro assays. Seven thousand (7,000) compounds were screened after computational...stim- ulation, and previous studies have demonstrated that cholesterol canbeused as a precursor for androgen synthesis (6, 26). Thus, the impact of

  6. Genome sequence of the Bacteroides fragilis phage ATCC 51477-B1

    Directory of Open Access Journals (Sweden)

    Hawkins Shawn A

    2008-08-01

    Full Text Available Abstract The genome of a fecal pollution indicator phage, Bacteroides fragilis ATCC 51477-B1, was sequenced and consisted of 44,929 bases with a G+C content of 38.7%. Forty-six putative open reading frames were identified and genes were organized into functional clusters for host specificity, lysis, replication and regulation, and packaging and structural proteins.

  7. Cleanup Verification Package for the 118-B-1, 105-B Solid Waste Burial Ground

    International Nuclear Information System (INIS)

    Capron, J.M.

    2008-01-01

    This cleanup verification package documents completion of remedial action, sampling activities, and compliance criteria for the 118-B-1, 105-B Solid Waste Burial Ground. This waste site was the primary burial ground for general wastes from the operation of the 105-B Reactor and P-10 Tritium Separation Project and also received waste from the 105-N Reactor. The burial ground received reactor hardware, process piping and tubing, fuel spacers, glassware, electrical components, tritium process wastes, soft wastes and other miscellaneous debris

  8. Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

    International Nuclear Information System (INIS)

    Trubicka, Joanna; Byrski, Tomasz; Gronwald, Jacek; Złowocka, Elżbieta; Kładny, Józef; Banaszkiewicz, Zbigniew; Wiśniowski, Rafał; Kowalska, Elżbieta; Lubinski, Jan; Scott, Rodney J; Grabowska-Kłujszo, Ewa; Suchy, Janina; Masojć, Bartłomiej; Serrano-Fernandez, Pablo; Kurzawski, Grzegorz; Cybulski, Cezary; Górski, Bohdan; Huzarski, Tomasz

    2010-01-01

    CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs), it represents an attractive candidate gene for studies into colorectal cancer susceptibility. We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations

  9. Stratigraphic structure of the B1 Tertiary tectonostratigraphic unit in eastern Slovenia

    Directory of Open Access Journals (Sweden)

    Bogomir Jelen

    2002-06-01

    Full Text Available High inconsistency and incoherence in the stratigraphy of the Slovenian upper Paleogene and lower Miocene have remained unsolved in the past 150 years. To solve the problem, we tried to rigorously conduct the authentic Galilei’s scientific method. Steps of logical and empirical verification confirmed the existence of the posited B1 Tertiary tectonostratigraphic unit, and a general chronostratigraphic model of new positional relationships of lithologic units resulted from rather good biochronostratigraphic resolution achieved by nannoplankton and planktonic foraminifera biostratigraphy. The application of principles of newly developed fields in science helped us to avoid errors in transmission of messages (to reduce noise from the source (rock to the concept formation,which had been done previously. This in turn has strongly reduced inconsistency andincoherence (high information entropy = uncertainty. The released amount of information enabled us to answer also questions that reached beyond the original difficulty, e.g.: is the tectonostratigraphic structure of eastern Slovenia a manifestation of plate tectonics processes, and of which ones, are theories of continental escape in the Alps and associated dissection and offset of the formerly uniform Slovenian-Hungarian Paleogene basin tenableor not, are then there in the B1 stratigraphic equivalents of the Hungarian Paleogene basin formations, where are the important Eocene / Oligocene, Paleogene / Neogene, Rupelian / Chattian and Kiscellian / Egerian boundaries in Slovenia, and is there acontinuation of the B1 in Croatia and in the Mid-Hungarian tectonic zone?

  10. Denoising of B1+ field maps for noise-robust image reconstruction in electrical properties tomography

    International Nuclear Information System (INIS)

    Michel, Eric; Hernandez, Daniel; Cho, Min Hyoung; Lee, Soo Yeol

    2014-01-01

    Purpose: To validate the use of adaptive nonlinear filters in reconstructing conductivity and permittivity images from the noisy B 1 + maps in electrical properties tomography (EPT). Methods: In EPT, electrical property images are computed by taking Laplacian of the B 1 + maps. To mitigate the noise amplification in computing the Laplacian, the authors applied adaptive nonlinear denoising filters to the measured complex B 1 + maps. After the denoising process, they computed the Laplacian by central differences. They performed EPT experiments on phantoms and a human brain at 3 T along with corresponding EPT simulations on finite-difference time-domain models. They evaluated the EPT images comparing them with the ones obtained by previous EPT reconstruction methods. Results: In both the EPT simulations and experiments, the nonlinear filtering greatly improved the EPT image quality when evaluated in terms of the mean and standard deviation of the electrical property values at the regions of interest. The proposed method also improved the overall similarity between the reconstructed conductivity images and the true shapes of the conductivity distribution. Conclusions: The nonlinear denoising enabled us to obtain better-quality EPT images of the phantoms and the human brain at 3 T

  11. Electrochemical Immunosensor Based on Polythionine/Gold Nanoparticles for the Determination of Aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Joseph H.O. Owino

    2008-12-01

    Full Text Available An aflatoxin B1 (AFB1 electrochemical immunosensor was developed by the immobilisation of aflatoxin B1-bovine serum albumin (AFB1-BSA conjugate on a polythionine (PTH/gold nanoparticles (AuNP-modified glassy carbon electrode (GCE. The surface of the AFB1-BSA conjugate was covered with horseradish peroxidase (HRP, in order to prevent non-specific binding of the immunosensors with ions in the test solution. The AFB1 immunosensor exhibited a quasi-reversible electrochemistry as indicated by a cyclic voltammetric (CV peak separation (ΔEp value of 62 mV. The experimental procedure for the detection of AFB1 involved the setting up of a competition between free AFB1 and the immobilised AFB1-BSA conjugate for the binding sites of free anti-aflatoxin B1 (anti-AFB1 antibody. The immunosensor’s differential pulse voltammetry (DPV responses (peak currents decreased as the concentration of free AFB1 increased within a dynamic linear range (DLR of 0.6 - 2.4 ng/mL AFB1 and a limit of detection (LOD of 0.07 ng/mL AFB1. This immunosensing procedure eliminates the need for enzyme-labeled secondary antibodies normally used in conventional ELISA–based immunosensors.

  12. Facile synthesis of cyclopentenone B1- and L1-type Phytoprostanes

    Directory of Open Access Journals (Sweden)

    Alexandre eGuy

    2015-07-01

    Full Text Available Phytoprostanes (PhytoPs represent non-enzymatic metabolites of α-linolenic acid (ALA, the essential omega-3 polyunsaturated fatty acid (PUFA derived from plants. PhytoPs are present in the plant kingdom and represent endogenous mediators capable of protecting cells from oxidative stress damages in plants. Recently, it was found that such metabolites are present in cooking oil in high quantities, and also that B1-PhytoPs protect immature neurons from oxidant injury and promote differentiation of oligodendrocyte progenitors through PPAR-γ activation. We report a novel and facile synthesis of natural 2,3-substituted cyclopentenone PhytoPs, 16-B1-PhytoP and 9-L1-PhytoP. Our strategy is based on reductive alkylation at the 2-position of 1,3-cyclopentanedione using a recent protocol developed by Ramachary et al., and on a cross-coupling metathesis to access conjugate dienone system. In conclusion, this strategy permitted access to B1- and L1-PhytoPs in a relative short sequence process, and afford the possibility to easily develop analogs of PhytoPs.

  13. Final characterization report for the 104-B-1 Tritium Vault and 104-B-2 Tritium Laboratory

    International Nuclear Information System (INIS)

    Encke, D.B.; Harris, R.A.

    1996-11-01

    This report is a compilation of the characterization data collected from the 104-B-1 Tritium Vault and the 104-B-2 Trillium Laboratory. The characterization activities were organized and implemented to evaluate the radiological status and identify any hazardous materials. The data contained in this report reflects the current conditions and status of the 104-B-1 Tritium Vault and 104-B-2 Tritium Laboratory. This information is intended to be utilized in support of future building decontamination and demolition, to allow for proper disposal of the demolition debris as required by the Washington Administrative Code, WAC 173-303, the Hanford Site Solid Waste Acceptance Criteria, WHC-EP-0063, and the Environmental Restoration Disposal Facility Waste Acceptance Criteria, BHI-00139. Based on the historical information and facility inspections, the only hazardous materials sampling and analysis activities necessary were to identify lead paint and asbestos containing materials (ACM) in the 104-B-1 Tritium Vault and the 104-B-2 Tritium Laboratory. Asbestos samples were obtained from the outer boundary of the roof areas to confirm the presence and type of asbestos containing fibers. Lead paint samples were obtained to confirm the presence and quantity of lead paint on the roof trim, doors and vents

  14. Evaluation of Extraction and Degradation Methods to Obtain Chickpeasaponin B1 from Chickpea (Cicer arietinum L.

    Directory of Open Access Journals (Sweden)

    Kun Cheng

    2017-02-01

    Full Text Available The objective of this research is to implement extraction and degradation methods for the obtainment of 3-O-[α-l-rhamnopyranosyl-(1→2-β-d-galactopyranosyl] soyasapogenol B (chickpeasaponin B1 from chickpea. The effects of microwave-assisted extraction (MAE processing parameters—such as ethanol concentration, solvent/solid ratio, extraction temperature, microwave irradiation power, and irradiation time—were evaluated. Using 1g of material with 8 mL of 70% aqueous ethanol and an extraction time of 10 min at 70 °C under irradiation power 400W provided optimal extraction conditions. Compared with the conventional extraction techniques, including heat reflux extraction (HRE, Soxhlet extraction (SE, and ultrasonic extraction (UE, MAE produced higher extraction efficiency under a lower extraction time. DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one saponin can be degraded to structurally stable saponin B by the loss of its DDMP group. The influence of pH and the concentration of potassium hydroxide on transformation efficiency of the target compound was investigated. A solution of 0.25 M potassium hydroxide in 75% aqueous ethanol was suitable for converting the corresponding DDMP saponins of chickpeasaponin B1. The implementation by the combining MAE technique and alkaline hydrolysis method for preparing chickpeasaponin B1 provides a convenient technology for future applications.

  15. Evaluation of Extraction and Degradation Methods to Obtain Chickpeasaponin B1 from Chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Cheng, Kun; Gao, Hua; Wang, Rong-Rong; Liu, Yang; Hou, Yu-Xue; Liu, Xiao-Hong; Liu, Kun; Wang, Wei

    2017-02-21

    The objective of this research is to implement extraction and degradation methods for the obtainment of 3- O -[α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranosyl] soyasapogenol B (chickpeasaponin B1) from chickpea. The effects of microwave-assisted extraction (MAE) processing parameters-such as ethanol concentration, solvent/solid ratio, extraction temperature, microwave irradiation power, and irradiation time-were evaluated. Using 1g of material with 8 mL of 70% aqueous ethanol and an extraction time of 10 min at 70 °C under irradiation power 400W provided optimal extraction conditions. Compared with the conventional extraction techniques, including heat reflux extraction (HRE), Soxhlet extraction (SE), and ultrasonic extraction (UE), MAE produced higher extraction efficiency under a lower extraction time. DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4 H -pyran-4-one) saponin can be degraded to structurally stable saponin B by the loss of its DDMP group. The influence of pH and the concentration of potassium hydroxide on transformation efficiency of the target compound was investigated. A solution of 0.25 M potassium hydroxide in 75% aqueous ethanol was suitable for converting the corresponding DDMP saponins of chickpeasaponin B1. The implementation by the combining MAE technique and alkaline hydrolysis method for preparing chickpeasaponin B1 provides a convenient technology for future applications.

  16. Preliminary investigations on B0 and B1 parameters of equatorial ionospheric profiles

    International Nuclear Information System (INIS)

    Adeniyi, J.O.

    1997-01-01

    The data used for this study are those from Ouagadougou (Lat. 12.4 deg. N, Dip 5.9 deg. N) and Ibadan (Lat. 7.4 deg. N, Dip 6.3 deg. S). Analysis were done for only daytime period. The results indicate that B0 exhibit a solar zenith angle dependent diurnal variation and some seasonal effect is presented during certain hours of the day. B1 does not show pronounced seasonal effects or solar zenith angle dependence. Daytime average value of B0 varied from 70 to 180 while B1 varied from 1.5 to 3.1. The average magnitudes of B0 at 1000,1200 and 1400 at Ibadan are greater than those of Ouagadougou during the winter season and the corresponding values of B1 are also greater in Ibadan during summer and winter seasons. In summer, average IRI B0 at 1200 hour for Ibadan is about the same as the experimental value but during winter, the IRI average is less than the experimental one. (author). 5 refs, 5 tabs

  17. Simultaneous use of linear and nonlinear gradients for B1+ inhomogeneity correction.

    Science.gov (United States)

    Ertan, Koray; Atalar, Ergin

    2017-09-01

    The simultaneous use of linear spatial encoding magnetic fields (L-SEMs) and nonlinear spatial encoding magnetic fields (N-SEMs) in B 1 + inhomogeneity problems is formulated and demonstrated with both simulations and experiments. Independent excitation k-space variables for N-SEMs are formulated for the simultaneous use of L-SEMs and N-SEMs by assuming a small tip angle. The formulation shows that, when N-SEMs are considered as an independent excitation k-space variable, numerous different k-space trajectories and frequency weightings differing in dimension, length, and energy can be designed for a given target transverse magnetization distribution. The advantage of simultaneous use of L-SEMs and N-SEMs is demonstrated by B 1 + inhomogeneity correction with spoke excitation. To fully utilize the independent k-space formulations, global optimizations are performed for 1D, 2D RF power limited, and 2D RF power unlimited simulations and experiments. Three different cases are compared: L-SEMs alone, N-SEMs alone, and both used simultaneously. In all cases, the simultaneous use of L-SEMs and N-SEMs leads to a decreased standard deviation in the ROI compared with using only L-SEMs or N-SEMs. The simultaneous use of L-SEMs and N-SEMs results in better B 1 + inhomogeneity correction than using only L-SEMs or N-SEMs due to the increased number of degrees of freedom. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Pharmacological characterization of homobaclofen on wild type and mutant GABA(B)1b receptors coexpressed with the GABA(B)2 receptor

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Madsen, Bo E.; Krogsgaard-Larsen, P

    2001-01-01

    homogenate and in an assay of electrically induced contractions of guinea pig ileum. The results from the two tissues did, however, not correlate very well, and in order to further investigate these discrepancies, we have pharmacologically characterized these enantiomers on recombinant wild type and mutant...... rat GABA(B)1b receptors coexpressed with rat GABA(B)2 receptors. The results from this study correlate nicely with the binding data from rat brain. (R)-Homobaclofen was shown to act like (R)-baclofen albeit with 20-fold less potency, and (S)-homobaclofen was inactive on the receptor. The discrepancies...

  19. Simulation of Fungal-Mediated Cell Death by Fumonisin B1 and Selection of Fumonisin B1–Resistant (fbr) Arabidopsis Mutants

    Science.gov (United States)

    Stone, Julie M.; Heard, Jacqueline E.; Asai, Tsuneaki; Ausubel, Frederick M.

    2000-01-01

    Fumonisin B1 (FB1), a programmed cell death–eliciting toxin produced by the necrotrophic fungal plant pathogen Fusarium moniliforme, was used to simulate pathogen infection in Arabidopsis. Plants infiltrated with 10 μM FB1 and seedlings transferred to agar media containing 1 μM FB1 develop lesions reminiscent of the hypersensitive response, including generation of reactive oxygen intermediates, deposition of phenolic compounds and callose, accumulation of phytoalexin, and expression of pathogenesis-related (PR) genes. Arabidopsis FB1-resistant (fbr) mutants were selected directly by sowing seeds on agar containing 1 μM FB1, on which wild-type seedlings fail to develop. Two mutants chosen for further analyses, fbr1 and fbr2, had altered PR gene expression in response to FB1. fbr1 and fbr2 do not exhibit differential resistance to the avirulent bacterial pathogen Pseudomonas syringae pv maculicola (ES4326) expressing the avirulence gene avrRpt2 but do display enhanced resistance to a virulent isogenic strain that lacks the avirulence gene. Our results demonstrate the utility of FB1 for high-throughput isolation of Arabidopsis defense-related mutants and suggest that pathogen-elicited programmed cell death of host cells may be an important feature of compatible plant–pathogen interactions. PMID:11041878

  20. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    Directory of Open Access Journals (Sweden)

    Adriana Frizzarin

    2012-12-01

    Full Text Available Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, pregnant women and elderly. The objective of this study was to detect the presence of B1 aflatoxin in feed supplied to dairy cows and the presence of M1 aflatoxin in milk. Samples were collected from complete diet (corn silage and concentrate from a batch of 15 lactating cows from a dairy farm in the Campinas region. Two samples of diets were collected directly into the troughs in intervals of 24 hours at every 15 days, totalizing a period of 45 days. Milk samples of those cows were collected 24 hours after diet collection, directly from sample valves in the glass jars.. B1 and M1 aflatoxins were detected by the technique of High Performance Liquid Chromatography after extraction and purification on immunoaffinity columns. From the 40 samples of diets evaluated, 40% were contaminated with B1 aflatoxin, and the levels found ranged from 1.93 to 43.78μg/Kg. One sample showed result higher than the maximum recommended for grain and animal feed in Brazil (20μg/Kg. From the 75 milk samples analyzed, the presence of M1 aflatoxin was detected in 13.3% with levels ranging from 0.03 to 0.16μg/L, not exceeding the maximum permitted for marketing in the country of 0.5μg/L, however 80% of contaminated samples had values above the maximum permissible levels of 0.05μg/L, value found among countries with abundant milk production... The presence of aflatoxins highlights the importance of monitoring the production, the storage and the importance of handling food and

  1. Effect of Aflatoxin B1 on Growth of Bovine Mammary Epithelial Cells in 3D and Monolayer Culture System.

    Science.gov (United States)

    Forouharmehr, Ali; Harkinezhad, Taher; Qasemi-Panahi, Babak

    2013-01-01

    Many studies have been showed transfer of aflatoxins, toxins produced by Aspergillus flvaus and Aspergillus parasiticus fungi, into milk. These toxins are transferred into the milk through digestive system by eating contaminated food. Due to the toxicity of these materials, it seems that it has side effects on the growth of mammary cells. Therefore, the present work aimed to investigate possible toxic effects of aflatoxin B1 (AFB1) on bovine mammary epithelial cells in monolayer and three-dimensional cultures. Specimens of the mammary tissue of bovine were sized out in size 2×2 cm in slaughterhouse. After disinfection and washing in sterile PBS, primary cell culture was performed by enzymatic digestion of tissue with collagenase. When proper numbers of cells were achieved in monolayer culture, cells were seeded in a 24-well culture plate for three-dimensional (3D) culture in Matrigel matrix. After 21 days of 3D culture and reaching the required number of cells, the concentrations of 15, 25 and 35 µL of AFB1 were added to the culture in quadruplicate and incubated for 8 hours. Cellular cytotoxicity was examined using standard colorimetric assay and finally, any change in the morphology of the cells was studied by microscopic technique. Microscopic investigations showed necrosis of the AFB1-exposed cells compared to the control cells. Also, bovine mammary epithelial cells were significantly affected by AFB1 in dose and time dependent manner in cell viability assays. According to the results, it seems that AFB1 can induce cytotoxicity and necrosis in bovine mammary epithelial cells.

  2. Effect of Aflatoxin B1 on Growth of Bovine Mammary Epithelial Cells in 3D and Monolayer Culture System

    Directory of Open Access Journals (Sweden)

    Babak Qasemi-Panahi

    2013-02-01

    Full Text Available Purpose: Many studies have been showed transfer of aflatoxins, toxins produced by Aspergillus flvaus and Aspergillus parasiticus fungi, into milk. These toxins are transferred into the milk through digestive system by eating contaminated food. Due to the toxicity of these materials, it seems that it has side effects on the growth of mammary cells. Therefore, the present work aimed to investigate possible toxic effects of aflatoxin B1 (AFB1 on bovine mammary epithelial cells in monolayer and three-dimensional cultures. Methods: Specimens of the mammary tissue of bovine were sized out in size 2×2 cm in slaughterhouse. After disinfection and washing in sterile PBS, primary cell culture was performed by enzymatic digestion of tissue with collagenase. When proper numbers of cells were achieved in monolayer culture, cells were seeded in a 24-well culture plate for three-dimensional (3D culture in Matrigel matrix. After 21 days of 3D culture and reaching the required number of cells, the concentrations of 15, 25 and 35 μL of AFB1 were added to the culture in quadruplicate and incubated for 8 hours. Cellular cytotoxicity was examined using standard colorimetric assay and finally, any change in the morphology of the cells was studied by microscopic technique. Results: Microscopic investigations showed necrosis of the AFB1-exposed cells compared to the control cells. Also, bovine mammary epithelial cells were significantly affected by AFB1 in dose and time dependent manner in cell viability assays. Conclusion: According to the results, it seems that AFB1 can induce cytotoxicity and necrosis in bovine mammary epithelial cells.

  3. Genetic modification of potato against microbial diseases: in vitro and in planta activity of a dermaseptin B1 derivative, MsrA2.

    Science.gov (United States)

    Osusky, Milan; Osuska, Lubica; Kay, William; Misra, Santosh

    2005-08-01

    Dermaseptin B1 is a potent cationic antimicrobial peptide found in skin secretions of the arboreal frog Phyllomedusa bicolor. A synthetic derivative of dermaseptin B1, MsrA2 (N-Met-dermaseptin B1), elicited strong antimicrobial activities against various phytopathogenic fungi and bacteria in vitro. To assess its potential for plant protection, MsrA2 was expressed at low levels (1-5 microg/g of fresh tissue) in the transgenic potato (Solanum tuberosum L.) cv. Desiree. Stringent challenges of these transgenic potato plants with a variety of highly virulent fungal phytopathogens--Alternaria, Cercospora, Fusarium, Phytophthora, Pythium, Rhizoctonia and Verticillium species--and with the bacterial pathogen Erwinia carotovora demonstrated that the plants had an unusually broad-spectrum and powerful resistance to infection. MsrA2 profoundly protected both plants and tubers from diseases such as late blight, dry rot and pink rot and markedly extended the storage life of tubers. Due to these properties in planta, MsrA2 is proposed as an ideal antimicrobial peptide candidate to significantly increase resistance to phytopathogens and improve quality in a variety of crops worldwide with the potential to obviate fungicides and facilitate storage under difficult conditions.

  4. Tissue engineering

    CERN Document Server

    Fisher, John P; Bronzino, Joseph D

    2007-01-01

    Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

  5. New function of the adaptor protein SH2B1 in brain-derived neurotrophic factor-induced neurite outgrowth.

    Directory of Open Access Journals (Sweden)

    Chien-Hung Shih

    Full Text Available Neurite outgrowth is an essential process for the establishment of the nervous system. Brain-derived neurotrophic factor (BDNF binds to its receptor TrkB and regulates axonal and dendritic morphology of neurons through signal transduction and gene expression. SH2B1 is a signaling adaptor protein that regulates cellular signaling in various physiological processes. The purpose of this study is to investigate the role of SH2B1 in the development of the central nervous system. In this study, we show that knocking down SH2B1 reduces neurite formation of cortical neurons whereas overexpression of SH2B1β promotes the development of hippocampal neurons. We further demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth and signaling using the established PC12 cells stably expressing TrkB, SH2B1β or SH2B1β mutants. Our data indicate that overexpressing SH2B1β enhances BDNF-induced MEK-ERK1/2, and PI3K-AKT signaling pathways. Inhibition of MEK-ERK1/2 and PI3K-AKT pathways by specific inhibitors suggest that these two pathways are required for SH2B1β-promoted BDNF-induced neurite outgrowth. Moreover, SH2B1β enhances BDNF-stimulated phosphorylation of signal transducer and activator of transcription 3 at serine 727. Finally, our data indicate that the SH2 domain and tyrosine phosphorylation of SH2B1β contribute to BDNF-induced signaling pathways and neurite outgrowth. Taken together, these findings demonstrate that SH2B1β promotes BDNF-induced neurite outgrowth through enhancing pathways involved MEK-ERK1/2 and PI3K-AKT.

  6. Amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole

    International Nuclear Information System (INIS)

    Saidov, D.K.; Rakhmonov, R.O.; Khodzhiboev, Yu.; Kukaniev, M.A.; Bandaev, S.

    2015-01-01

    Present article is devoted to amino methylation of 2-R-6-R_1-imidazo-[2.1-B]-1.3.4-thiadiazole. The reaction of new modifications of derivatives of imidazo-[2.1-B]-1.3.4-thiadiazoles-2-bromine-6-p-bromophenyl and 2-alkyl alkylene sulfonyl-6-phenyl imidazo--[2.1-B]-1.3.4-thiadiazole on Mannich with secondary and heterocyclic amines was studied.

  7. 40 CFR 721.9662 - Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro... Specific Chemical Substances § 721.9662 Thieno[3,4-b]-1,4-dioxin, 2,3-dihydro- (9CI). (a) Chemical...-b]-1,4-dioxin, 2,3-dihydro- (9CI) (PMN P-95-1825; CAS No. 126213-50-1) is subject to reporting under...

  8. Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena [Instituto De Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-07-01

    Full text: Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all renal cell carcinomas (RCC) and has the Von Hippel-Lindau (VHL) tumor suppressor gene mutated. The lack of VHL protein leads to a constitutionally active Hypoxia Inducible Factor (HIF) pathway that confers both chemoresistance and radioresistance for renal tumor. HIF pathway is known to interact with the transcription factor nuclear factor kappa B (NF-kB). Increased NF-κB activity is associated with the development and progression of RCC (IKEGAMI A, TEIXEIRA LF. BRAGA MS et al. The American Society for Cell Biology 2016; 26: 3948-3955). Objective: Evaluate the synergistic effect of NF-kB1 knockdown and ionizing radiation in murine renal adenocarcinoma cell line. Methods: The murine renal adenocarcinoma cell line (Renca cells) (ATCC, USA) was cultured in RPMI 1640 supplemented with 10% FBS and penicillin/streptomycin. Lentiviral shRNA vector was used to knockdown of NF-KB1 gene in Renca cells, as described previously (1). In the clonogenic cell survival assay, the cells were irradiated by {sup 60}Co source in the range from 0 to 10 Gy, using the GammaCell 220 – Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture, cell colonies were fixed and stained with formaldehyde 4% and rhodamine B 2% and counted. To assess cell viability, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-MTS] was performed within 24 hours after irradiation at a dose of 10Gy. The survival variables α e β were fitted according to the linear quadratic equation (SF=exp[-αD-βD2]); SF=survival fraction, D=dose of irradiation and P value was determined by F test. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. P< 0.05 was considered statistically significant. Data are shown as the mean ± SD. Results: The Renca-shRNA-NF-kB1 cells were found

  9. Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

    International Nuclear Information System (INIS)

    Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena

    2017-01-01

    Full text: Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all renal cell carcinomas (RCC) and has the Von Hippel-Lindau (VHL) tumor suppressor gene mutated. The lack of VHL protein leads to a constitutionally active Hypoxia Inducible Factor (HIF) pathway that confers both chemoresistance and radioresistance for renal tumor. HIF pathway is known to interact with the transcription factor nuclear factor kappa B (NF-kB). Increased NF-κB activity is associated with the development and progression of RCC (IKEGAMI A, TEIXEIRA LF. BRAGA MS et al. The American Society for Cell Biology 2016; 26: 3948-3955). Objective: Evaluate the synergistic effect of NF-kB1 knockdown and ionizing radiation in murine renal adenocarcinoma cell line. Methods: The murine renal adenocarcinoma cell line (Renca cells) (ATCC, USA) was cultured in RPMI 1640 supplemented with 10% FBS and penicillin/streptomycin. Lentiviral shRNA vector was used to knockdown of NF-KB1 gene in Renca cells, as described previously (1). In the clonogenic cell survival assay, the cells were irradiated by 60 Co source in the range from 0 to 10 Gy, using the GammaCell 220 – Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture, cell colonies were fixed and stained with formaldehyde 4% and rhodamine B 2% and counted. To assess cell viability, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-MTS] was performed within 24 hours after irradiation at a dose of 10Gy. The survival variables α e β were fitted according to the linear quadratic equation (SF=exp[-αD-βD2]); SF=survival fraction, D=dose of irradiation and P value was determined by F test. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. P< 0.05 was considered statistically significant. Data are shown as the mean ± SD. Results: The Renca-shRNA-NF-kB1 cells were found to be

  10. In vitro study of vitamins B1, B2 and B6 adsorption on zeolite

    Directory of Open Access Journals (Sweden)

    Basić Zorica

    2011-01-01

    Full Text Available Background/Aim. Zeolites are the hydratised alumosilicates of alcali and earthalcali cations, which have a long three-dimensional crystal structure. Preparations on the basis of zeolites are used for adsorption of organic and nonorganic toxic substances and they, also, find more and more use in veterinary and human medicine and pharmacy. The aim of this study was to evaluate the possibilities of zeolite to adsorb vitamins B1, B2 and B6 in acid and neutral solutions, as well as the characteristics of the process (saturability, reversibility and competitivness. Methods. The specific and sensitive HPLC method with fluorescent detector was used for determination of vitamins B1, B2 and B6. Analyte separation and detection were carried out by applying the reverse-phase method on column C18. An in vitro experiment was done by testing the influence of pH value (2 and 7, concentration of vitamin solution (1, 2 and 5 mg/L, the lenght of contact with zeolite (10-180 min and cation competitiveness on the exchange capacity, which is achieved by media and zeolite contact, as well as a possible vitamins desorption through changing pH value of the solution at 37°C. Jon competitiveness was examined by adding commercial feed mixture (grower with a defined content of the examined vitamines in zeolite solutions the pH = 2 and pH = 7. Results. Vitamins B1, B2 and B6 were stable in both pH=2 and pH = 7 solutions at 37°C, in the defined time intervals. In acid solution concentrations of vitamins significantly declined in the first 10 min, with no significant decline in further 30 min for all the three concentrations testch. In neutral solution, after the addition of 1% zeolite, decrease in vitamins concentrations was slightly lower than in acid solution, but also significant in the first 10 min of the contact with zeolite. It was found that zeolite, which adsorbed vitamins in acid solution, transferred in the neutral one released a significant quantity of adsorbed

  11. Evaluation of Pyrantel Pamoate, Nitramisole and Avermectin B1aAgainst Migrating Strongylus vulgaris Larvae‡

    Science.gov (United States)

    Slocombe, J. O. D.; McCraw, B. M.

    1980-01-01

    Trials were conducted in ponies to evaluate the efficacy of pyrantel pamoate (Strongid-T®) and two newer anthelmintics not yet commercially available, nitramisole and avermectin B1a, against migrating Strongylus vulgaris larvae. Ponies were removed from their mares within 24-48 hr after birth and reared in isolation, worm free. Between six and 14 weeks of age they were infected with 2000 or 2500 infective S. vulgaris larvae. Subsequently, they were monitored daily for clinical signs until the experiment terminated at 28 days postinfection. All ponies showed increased body temperature and reduced appetite within the first week of infection. All anthelmintics were administered on day 7 and in addition pyrantel pamoate was given on day 8 postinfection. The anthelmintics were in liquid formulation. Nitramisole and pyrantel pamoate were given by stomach tube and avermectin B1a by subcutaneous injection. Following administration of these compounds toxic reactions were not observed. All anthelmintics caused a reduction in body temperature and increased appetite and effected a clinical cure. In ponies which were not treated with an anthelmintic, temperatures remained elevated and appetites never returned completely to normal. These ponies also showed variable degrees of lethargy, depression, recumbency and colic and the majority died between two and three weeks postinfection. At necropsy, these control ponies showed variable degrees of adhesions involving the abdominal organs, necrosis of the ileum and cecum and severe arteritis and thrombosis of the major abdominal arteries and their branches. Although pyrantel pamoate, used at eight times the therapeutic dose for intestinal nematodes in the horse, effected a clinical cure it did not produce a radical cure. At necropsy, ponies treated with pyrantel pamoate had arteritis and thrombosis of the cranial mesenteric artery and its major branches. Nitramisole and avermectin B1a were able to effect both a clinical and radical

  12. Evaluation of pyrantel pamoate, nitramisole and avermectin B1a against migrating Strongylus vulgaris larvae.

    Science.gov (United States)

    Slocombe, J O; McCraw, B M

    1980-01-01

    Trials were conducted in ponies to evaluate the efficacy of pyrantel pamoate (Strongid-T(R)) and two newer anthelmintics not yet commercially available, nitramisole and avermectin B(1)a, against migrating Strongylus vulgaris larvae. Ponies were removed from their mares within 24-48 hr after birth and reared in isolation, worm free. Between six and 14 weeks of age they were infected with 2000 or 2500 infective S. vulgaris larvae. Subsequently, they were monitored daily for clinical signs until the experiment terminated at 28 days postinfection. All ponies showed increased body temperature and reduced appetite within the first week of infection. All anthelmintics were administered on day 7 and in addition pyrantel pamoate was given on day 8 postinfection. The anthelmintics were in liquid formulation. Nitramisole and pyrantel pamoate were given by stomach tube and avermectin B(1)a by subcutaneous injection.Following administration of these compounds toxic reactions were not observed. All anthelmintics caused a reduction in body temperature and increased appetite and effected a clinical cure. In ponies which were not treated with an anthelmintic, temperatures remained elevated and appetites never returned completely to normal. These ponies also showed variable degrees of lethargy, depression, recumbency and colic and the majority died between two and three weeks postinfection. At necropsy, these control ponies showed variable degrees of adhesions involving the abdominal organs, necrosis of the ileum and cecum and severe arteritis and thrombosis of the major abdominal arteries and their branches.Although pyrantel pamoate, used at eight times the therapeutic dose for intestinal nematodes in the horse, effected a clinical cure it did not produce a radical cure. At necropsy, ponies treated with pyrantel pamoate had arteritis and thrombosis of the cranial mesenteric artery and its major branches. Nitramisole and avermectin B(1)a were able to effect both a clinical and

  13. Milk kefir: ultrastructure, antimicrobial activity and efficacy on aflatoxin B1 production by Aspergillus flavus.

    Science.gov (United States)

    Ismaiel, Ahmed A; Ghaly, Mohamed F; El-Naggar, Ayman K

    2011-05-01

    The association of kefir microbiota was observed by electron microscopic examination. Scanning electron microscopic (SEM) observations revealed that kefir grain surface is very rough and the inner portions had scattered irregular holes on its surface. The interior of the grain comprised fibrillar materials which were interpreted as protein, lipid and a soluble polysaccharide, the kefiran complex that surrounds yeast and bacteria in the grain. Yeast was observed more clearly than bacteria on the outer portion of the grain. Transmission electron microscopic (TEM) observations of kefir revealed that the grain comprised a mixed culture of yeast and bacteria growing in close association with each other. Microbiota is dominated by budded and long-flattened yeast cells growing together with lactobacilli and lactococci bacteria. Bacterial cells with rounded ends were also observed in this mixed culture. Kefir grains, kefir suspensions, and kefiran were tested for antimicrobial activities against several bacterial and fungal species. The highest activity was obtained against Streptococcus faecalis KR6 and Fusarium graminearum CZ1. Growth of Aspergillus flavus AH3 producing for aflatoxin B1 for 10 days in broth medium supplemented with varying concentrations of kefir filtrate (%, v/v) showed that sporulation was completely inhibited at the higher concentrations of kefir filtrate (7-10%, v/v). The average values of both mycelial dry weights and aflatoxin B1 were completely inhibited at 10% (v/v). This is the first in vitro study about the antifungal characteristics of kefir against filamentous fungi which was manifested by applying its inhibitory effect on the productivity of aflatoxin B1 by A. flavus AH3.

  14. The CHESS survey of the L1157-B1 bow-shock: Dissecting the water content

    Science.gov (United States)

    Busquet, Gemma; Lefloch, Bertrand; Benedettini, Milena; Ceccarelli, Cecilia; Codella, Claudio; Cabrit, Sylvie; Nisini, Brunella; Viti, Serena; Gómez-Ruiz, Arturo; Gusdorf, Antoine; Di Giorgio, Anna Maria; Wiesenfeld, Laurent

    2013-07-01

    Molecular outflows powered by young protostars strongly affect the kinematics and chemistry of the natal molecular cloud through strong shocks, resulting in an increase of the abundance of several species. In particular, water is a powerful tracer of shocked material due to its sensitivity to both physical conditions and chemical processes. The observations of the "Chemical Herschel Survey of Star forming regions" (CHESS) key program towards the shock region L1157-B1 offered a unique and comprehensive view of the water emission in a typical protostellar bow shock across the submillimeter and far-infrared window. A grand total of 13 water lines have been detected with the PACS and HIFI instruments, probing a wide range of excitation conditions and providing us with a detailed picture on both the kinematics and the spatial distribution of water emission. Several gas components have been identified coexisting in the L1157-B1 shock region. Large Velocity Gradient (LVG) analysis reveals that these components have different excitation conditions: i) a warm (T~250 K) and dense (n(H2)~10^6 cm-3) gas component seen also with the CO lines and associated with the partly dissociative shock produced by the impact of the protostellar jet against the bow shock; ii) a compact (size~5''), hot (T~700 K), and less dense (n(H2)~10^4 cm-3) gas component, and iii) an extended component associated with the B1 outflow cavity. These three components present clear differences in terms of water enrichment. Finally, we confront the physical and chemical properties of the H2O emission to the predictions of current shock models.

  15. Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility

    Directory of Open Access Journals (Sweden)

    Trubicka Joanna

    2010-08-01

    Full Text Available Abstract Background CYP1B1 is a P450 enzyme which is involved in the activation of pro-carcinogens to carcinogens as well as sex hormone metabolism. Because differences in the activity of the enzyme have been correlated with variant alleles of single nucleotide polymorphisms (SNPs, it represents an attractive candidate gene for studies into colorectal cancer susceptibility. Methods We genotyped 597 cancer patients and 597controls for three CYP1B1 SNPs, which have previously been shown to be associated with altered enzymatic activity. Using the three SNPs, eight different haplotypes were constructed. The haplotype frequencies were estimated in cases and controls and then compared. The odds ratio for each tumour type, associated with each haplotype was estimated, with reference to the most common haplotype observed in the controls. Results The three SNPs rs10012, rs1056827 and rs1056836 alone did not provide any significant evidence of association with colorectal cancer risk. Haplotypes of rs1056827 and rs10012 or rs1056827 and rs1056836 revealed an association with colorectal cancer which was significantly stronger in the homozygous carriers. One haplotype was under represented in the colorectal cancer patient group compared to the control population suggesting a protective effect. Conclusion Genetic variants within the CYP1B1 that are associated with altered function appear to influence susceptibility to a colorectal cancer in Poland. Three haplotypes were associated with altered cancer risk; one conferred protection and two were associated with an increased risk of disease. These observations should be confirmed in other populations.

  16. Identification of a novel antagonist of the ErbB1 receptor capable of inhibiting migration of human glioblastoma cells

    DEFF Research Database (Denmark)

    Staberg, Mikkel; Riemer, Christian; Xu, Ruodan

    2013-01-01

    B1 targeting peptide, termed Herfin-1, was designed based on a model of the tertiary structure of the EGF-EGFR ternary complex. The binding kinetics of this peptide were determined employing surface plasmon resonance analyses. ErbB1-4 expression and phosphorylation in human glioblastoma cell lines U...... processing. RESULTS: The present study shows that Herfin-1 functions as an ErbB1 antagonist. It binds to the extracellular domain of ErbB1 with a KD value of 361 nM. In U87 and U118 cells, both expressing high levels of ErbB1, Herfin-1 inhibits EGF-induced ErbB1 phosphorylation and cell migration....... Additionally, Herfin-1 was found to increase neurite outgrowth in cerebellar granule neurons, likely through the inhibition of a sustained weak ErbB1 activation. CONCLUSIONS: Targeting the ErbB1 receptor dimerization interface is a promising strategy to inhibit receptor activation in ErbB1-expressing glioma...

  17. Decreased internalisation of erbB1 mutants in lung cancer is linked with a mechanism conferring sensitivity to gefitinib.

    Science.gov (United States)

    Hendriks, B S; Griffiths, G J; Benson, R; Kenyon, D; Lazzara, M; Swinton, J; Beck, S; Hickinson, M; Beusmans, J M; Lauffenburger, D; de Graaf, D

    2006-11-01

    A majority of gefitinib (IRESSA)-responsive tumours in non-small cell lung cancer have been found to carry mutations in ErbB1. Previously, it has been observed that internalisation-deficient ErbB1 receptors are strong drivers of oncogenesis. Using a computational model of ErbB1 trafficking and signalling, it is found that a deficiency in ErbB1 internalisation is sufficient to explain the observed signalling phenotype of these gefitinib-responsive ErbB1 mutants in lung cancer cell lines. Experimental tests confirm that gefitinib-sensitive cell lines with and without ErbB1 mutations exhibit markedly slower internalisation rates than gefitinib-insensitive cell lines. Moreover, the computational model demonstrates that reduced ErbB1 internalisation rates are mechanistically linked to upregulated AKT signalling. Experimentally it is confirmed that impaired internalisation of ErbB1 is associated with increased AKT activity, which can be blocked by gefitinib. On the basis of these experimental and computational results, it is surmised that gefitinib sensitivity is a marker of a reliance on AKT signalling for cell survival that may be brought about by impaired ErbB1 internalisation.

  18. Heterogeneous nuclear ribonucleoprotein B1 protein impairs DNA repair mediated through the inhibition of DNA-dependent protein kinase activity

    International Nuclear Information System (INIS)

    Iwanaga, Kentaro; Sueoka, Naoko; Sato, Akemi; Hayashi, Shinichiro; Sueoka, Eisaburo

    2005-01-01

    Heterogeneous nuclear ribonucleoprotein B1, an RNA binding protein, is overexpressed from the early stage of lung cancers; it is evident even in bronchial dysplasia, a premalignant lesion. We evaluated the proteins bound with hnRNP B1 and found that hnRNP B1 interacted with DNA-dependent protein kinase (DNA-PK) complex, and recombinant hnRNP B1 protein dose-dependently inhibited DNA-PK activity in vitro. To test the effect of hnRNP B1 on DNA repair, we performed comet assay after irradiation, using normal human bronchial epithelial (HBE) cells treated with siRNA for hnRNP A2/B1: reduction of hnRNP B1 treated with siRNA for hnRNP A2/B1 induced faster DNA repair in normal HBE cells. Considering these results, we assume that overexpression of hnRNP B1 occurring in the early stage of carcinogenesis inhibits DNA-PK activity, resulting in subsequent accumulation of erroneous rejoining of DNA double-strand breaks, causing tumor progression

  19. Suicidal gene therapy with rabbit cytochrome P450 4B1/4-ipomeanol, 2-aminoanthracene system in glioma cell

    International Nuclear Information System (INIS)

    Jang, Su Jin; Kang, Joo Hyun; Kim, Kwang Il; Lee, Tae Sup; Lee, Yong Jin; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

    2010-01-01

    Suicidal gene therapy is based on the transduction of tumor cells with 'suicide' genes encoding for prodrugactivating enzymes that render target cells susceptible to prodrug treatment. Suicidal gene therapy results in the death of tumor with the expression of gene encoding enzyme that converts non-toxic prodrug into cytotoxic product. Cytochrome P450 4B1 (CYP4B1) activates 4- ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) to cytotoxic furane epoxide and unsaturated dialdehyde intermediate. In this study, therapeutic effects of suicidal gene therapy with rabbit CYP4B1/4-ipo or CYP4B1/2-AA system

  20. Suicidal gene therapy with rabbit cytochrome P450 4B1/4-ipomeanol, 2-aminoanthracene system in glioma cell

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Su Jin; Kang, Joo Hyun; Kim, Kwang Il; Lee, Tae Sup; Lee, Yong Jin; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2010-10-15

    Suicidal gene therapy is based on the transduction of tumor cells with 'suicide' genes encoding for prodrugactivating enzymes that render target cells susceptible to prodrug treatment. Suicidal gene therapy results in the death of tumor with the expression of gene encoding enzyme that converts non-toxic prodrug into cytotoxic product. Cytochrome P450 4B1 (CYP4B1) activates 4- ipomeanol (4-ipo) and 2-aminoanthracene (2-AA) to cytotoxic furane epoxide and unsaturated dialdehyde intermediate. In this study, therapeutic effects of suicidal gene therapy with rabbit CYP4B1/4-ipo or CYP4B1/2-AA system

  1. Targeting Sulfotransferase (SULT) 2B1b as a Regulator of Cholesterol Metabolism in Prostate Cancer

    Science.gov (United States)

    2015-10-01

    next  subtask.       Subtask 2: Production of infective Lentivirus using co-transfection of HEK293 (pCa cells LNCaP, PC3, DU145, and VCaP...PCa lines. We determined that the level of shRNA expression from a stably intergrated transgene gene delivered by lentivirus was too low...effects  on  SULT2B1b  enzyme  activity  of   cholesterol  sulfate   production  in  vitro.     We  developed  a

  2. Emericella astellata, a new producer of aflatoxin B-1, B-2 and sterigmatocystin

    DEFF Research Database (Denmark)

    Frisvad, Jens Christian; Samson, R.A.; Smedsgaard, Jørn

    2004-01-01

    To report on aflatoxin B-1 and B-2 production from a species of Emericella. Methods and Results: Aflatoxins and sterigmatocystin were determined by high-pressure liquid chromatography (HPLC) with diode array detection and confirmed by HPLC with mass spectrometry detection. Among 30 known species...... of Emericella only one species produced aflatoxin. Strains originating from the same geographical source material had different patterns of aflatoxin and sterigmatocystin production on different media, indicating that epigenetic factors may be involved in the regulation of aflatoxin production. However, two...

  3. Degradation of Aflatoxin B1 during the Fermentation of Alcoholic Beverages

    OpenAIRE

    Inoue, Tomonori; Nagatomi, Yasushi; Uyama, Atsuo; Mochizuki, Naoki

    2013-01-01

    Aflatoxin B1 (AFB1) is a contaminant of grain and fruit and has one of the highest levels of carcinogenicity of any natural toxin. AFB1 and the fungi that produce it can also contaminate the raw materials used for beer and wine manufacture, such as corn and grapes. Therefore, brewers must ensure strict monitoring to reduce the risk of contamination. In this study, the fate of AFB1 during the fermentation process was investigated using laboratory-scale bottom and top beer fermentation and wine...

  4. Detoxification of aflatoxin B1 in poultry and fish feed by various chemicals

    International Nuclear Information System (INIS)

    Nisa, A.U.; Hina, S.; Ejaz, N.

    2012-01-01

    In this study various poultry and fish feed samples were initially analyzed for presence of aflatoxin. All the samples were found contaminated with aflatoxin B I only. Contaminated samples were treated with different organic and inorganic chemicals to detoxify aflatoxin B 1 in poultry and fish feed samples. The maximum reduction in the aflatoxin Bl concentration was observed with 0.5% HCI as 14.20 ppb to 2.09 ppb (86.50%) in the poultry and 69.26 ppb to 10.46 ppb (84.89%) in fish feed samples.

  5. 2-Isobutyl-6-(4-methoxyphenylimidazo[2,1-b][1,3,4]thiadiazole

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2011-02-01

    Full Text Available In the title compound, C15H17N3OS, the dihedral angle between the statistically planar imidazo[2,1-b][1,3,4]thiadiazole fused-ring system (r.m.s. deviation = 0.002 Å and the methyoxbenzene ring is 4.52 (6°. In the crystal, molecules are arranged into columns and stacked down the a axis. The crystal structure is stabilized by weak C—H...π and π–π interactions [centroid–centroid separations = 3.6053 (8 and 3.7088 (7 Å].

  6. Aflatoxin B1 and sterigmatocystin survey in beer sold in China.

    Science.gov (United States)

    Zhao, Yarong; Huang, Jianxiang; Ma, Liyan; Liu, Shuai; Wang, Fuhua

    2017-03-01

    A total of 101 samples of beer from the Chinese market were analysed for the presence of aflatoxin B 1 (AFB 1 ) and sterigmatocystin (STC), using methods based on liquid chromatography-tandem mass spectrometry. The limit of quantification and the limit of detection in beer were 0.1 and 0.03 µg/kg, respectively. Recoveries of AFB 1 and STC from spiked beer samples were 97.8-103.6% and 92.7-102.1%, respectively. None of the beer purchased samples were contaminated with AFB 1 or STC.

  7. Effect of Mycoplasma hyopneumoniae and fumonisin B1 toxin on the lung in pigs

    Directory of Open Access Journals (Sweden)

    Melinda Kovács

    2010-01-01

    Full Text Available The authors examined the combined effect of Mycoplasma hyopneumoniae (Mh and fumonisin B1 (FB1 mycotoxin in pigs. Computed tomography (CT was applied to follow up the pathological events in the lung. Piglets were infected with Mh, or treated with FB1, or both infected and treated with Mh and FB1. The Mh infection produced lung lesions in all piglets the severity of which was increased by FB1. The CT is a suitable method for studying the pathological conditions in the lower respiratory tract of swine.

  8. Genetic variation of Aflatoxin B(1) aldehyde reductase genes (AFAR) in human tumour cells

    DEFF Research Database (Denmark)

    Praml, Christian; Schulz, Wolfgang; Claas, Andreas

    2008-01-01

    AFAR genes play a key role in the detoxification of the carcinogen Aflatoxin B(1) (AFB(1)). In the rat, Afar1 induction can prevent AFB(1)-induced liver cancer. It has been proposed that AFAR enzymes can metabolise endogenous diketones and dialdehydes that may be cytotoxic and/or genotoxic. Furth...... many aldo-keto reductases. This polarity change may have an effect on the proposed substrate binding amino acids nearby (Met(47), Tyr(48), Asp(50)). Further population analyses and functional studies of the nine variants detected may show if these variants are disease-related....

  9. Yeast cell based feed additives: Studies on aflatoxin B1 and zearalenone

    OpenAIRE

    2011-01-01

    Abstract Thirty commercially available yeast cell wall products and two reference bentonites were tested for their ability to bind aflatoxin B1 (AFB1) and zearalenone (ZON) in buffer solutions at pH 3 and pH 6.5 as well as in real gastric juice. For most products, the binding efficacy of AFB1 correlated with the ash content which was between 2.6 and 89% and constituted the inorganic non-volatile components, like mineral clays, of the samples. Samples with smectite as main ash compo...

  10. Evaluation of Extraction and Degradation Methods to Obtain Chickpeasaponin B1 from Chickpea (Cicer arietinum L.)

    OpenAIRE

    Kun Cheng; Hua Gao; Rong-Rong Wang; Yang Liu; Yu-Xue Hou; Xiao-Hong Liu; Kun Liu; Wei Wang

    2017-01-01

    The objective of this research is to implement extraction and degradation methods for the obtainment of 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-galactopyranosyl] soyasapogenol B (chickpeasaponin B1) from chickpea. The effects of microwave-assisted extraction (MAE) processing parameters—such as ethanol concentration, solvent/solid ratio, extraction temperature, microwave irradiation power, and irradiation time—were evaluated. Using 1g of material with 8 mL of 70% aqueous ethanol and an extraction t...

  11. TU-H-206-03: Characterizing B1 Inhomogeneities in DCE MRI

    International Nuclear Information System (INIS)

    Gach, H; Mason, N

    2016-01-01

    Purpose: Dynamic Contrast Enhanced (DCE) MRI is a valuable technique for measuring perfusion and permeability characteristics of tumors. Exogenous contrast concentrations are calculated based on changes in T 1 measured using fast 3D gradient echo (FLASH) sequences. However, the slab selective pulses used in 3D MRI may result in B 1 inhomogeneities across the volume of interest that can lead to errors in T 1 and thus the estimated gadolinium concentration. We compared three FLASH DCE sequences (GRE, TWIST, and VIBE) to determine their signal homogeneity across slices and the accuracy in calculating T 1 using acquisitions with variable flip angles. Methods: The sequences were tested at 3 T on a Siemens mMR (VB20P) using a doped water phantom 3.75 g/L NiSO 4 - 6H 2 O + 5 g/L NaCl (T 1 = 104 ms) and a 2% agar, 0.67% NaCl phantom (T 1 = 1.71 s). 2D EPI B 1 maps and inversion recovery T 1 maps were acquired for ground truth. 3D MRI was acquired at different flip angles to generate a T 1 map. Regions of interest were drawn to measure signal inside the phantoms as a function of slice position. The T 1 for each slice ROI was fit to the FLASH steady-state model of magnetization. Results: Based on the data, GRE gave the most uniform signal homogeneity and T 1 values in the middle slices of the 3D volume. The 3D VIBE sequence had the largest region of signal inhomogeneity compared to the 3D GRE and TWIST sequences. VIBE’s B 1 inhomogeneity is inconsistent at low flip angles. However, VIBE resulted in more slices with T 1 values similar to the ground truth. Conclusion: The central 1/3 of the slices yielded signals that result in T 1 fits consistent with the ground truth. However, the remaining slices required some form of B 1 inhomogeneity correction for quantitative DCE analysis. The research was supported in part by NIH NCI Grant R01CA159471.

  12. In vitro study of vitamins B1, B2 and B6 adsorption on zeolite

    OpenAIRE

    Basić Zorica; Kilibarda Vesna; Dobrić Silva; Resanović Radmila

    2011-01-01

    Background/Aim. Zeolites are the hydratised alumosilicates of alcali and earthalcali cations, which have a long three-dimensional crystal structure. Preparations on the basis of zeolites are used for adsorption of organic and nonorganic toxic substances and they, also, find more and more use in veterinary and human medicine and pharmacy. The aim of this study was to evaluate the possibilities of zeolite to adsorb vitamins B1, B2 and B6 in acid and neutral solutions, as well as the chara...

  13. Numerical study of the static and pitching RISØ-B1-18 airfoil

    DEFF Research Database (Denmark)

    Bertagnolio, Franck

    2004-01-01

    The objective of this report is the better understanding of the physics of the aeroelastic motion of wind turbine blades in order to improve the numerical models used for their design. In this study, the case of the RISØ-B1-18 airfoil which was equippedand measured in an open jet wind tunnel...... that are available both for the static airfoil and in the case of pitching motions. It is shown that the Navier-Stokes simulations can reproduced the maincharacteristic features of the flow. The DES model seems also to be able to reproduce some details of the unsteady aerodynamics. The Navier-Stokes computations can...

  14. RIN4 recruits the exocyst subunit EXO70B1 to the plasma membrane

    Czech Academy of Sciences Publication Activity Database

    Sabol, P.; Kulich, I.; Žárský, Viktor

    2017-01-01

    Roč. 68, č. 12 (2017), s. 3253-3265 ISSN 0022-0957 R&D Projects: GA ČR(CZ) GA15-14886S Institutional support: RVO:61389030 Keywords : oligomeric golgi-complex * powdery mildew fungus * pseudomonas-syringae * cell polarity * arabidopsis * protein * plants * resistance * expression * transport * Autophagy * exo70b1 * exo70b2 * exocyst * plant immunity * rin4 * secretion Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 5.830, year: 2016

  15. Identification of N-acyl-fumonisin B1 as new cytotoxic metabolites of fumonisin mycotoxins.

    Science.gov (United States)

    Harrer, Henning; Laviad, Elad L; Humpf, Hans Ulrich; Futerman, Anthony H

    2013-03-01

    Fumonisins are mycotoxins produced by Fusarium species. The predominant derivative, fumonisin B1 (FB1), occurs in food and feed and is of health concern due to its hepatotoxic and carcinogenic effects. However, the role of FB1 metabolites on the mechanism of the toxicity, the inhibition of the ceramide synthesis, is unknown. The aim of this study was to identify new fumonisin metabolites and to evaluate their cytotoxic potential. MS, molecular biology, and in vitro enzyme assays were used to investigate fumonisin metabolism in mammalian cells overexpressing human ceramide synthase (CerS) genes. N-acyl-FB1 derivatives were detected as new metabolites in cultured cells at levels of up to 10 pmol/mg of protein. The N-acylation of FB1 and hydrolyzed FB1 was analyzed in several cell lines, including cells overexpressing CerS. The acyl-chain length of the N-acyl fumonisins depends on the CerS isoform acylating them. The N-acyl fumonisins are more cytotoxic than the parent fumonisin B1. The identification of N-acyl fumonisins with various acyl chain lengths together with the observed cytotoxicity of these compounds is a new aspect of fumonisin-related toxicity. Therefore, these new metabolites might play an important role in the mode of action of fumonisins. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. High-sensitivity immunochromatographic assay for fumonisin B1 based on indirect antibody labeling.

    Science.gov (United States)

    Urusov, Alexandr E; Petrakova, Alina V; Gubaydullina, Milyausha K; Zherdev, Anatoly V; Eremin, Sergei A; Kong, Dezhao; Liu, Liqiang; Xu, Chuanlai; Dzantiev, Boris B

    2017-05-01

    To develop a high-sensitivity immunochromatographic test for fumonisin B1 in plant extracts. Unlike conventional immunochromatographic tests, this assay is performed in two stages: competitive reaction with free specific antibodies and identifying immune complexes by their interaction with the anti-species antibody-conjugated gold nanoparticles. The use of a new geometry for the test strip membranes and a novel reagent application method ensures the proper order of these stages without additional manipulations. The contact of the ready-to-use test strip with the liquid sample suffices in initiating all stages of the assay and obtaining test results. The developed test was used on corn extracts; its instrumental limit of fumonisin B1 detection was 0.6 ng ml -1 at 15 min of assay duration. The proposed approach is flexible and can be used for a wide range of low molecular compounds. The use of anti-species antibody-conjugated gold nanoparticles in immunochromatography significantly facilitates the development of test systems by eliminating the need to synthesize and characterize the conjugates with specific antibodies for each new compound to be detected.

  17. Pressure dependent elastic and structural (B3-B1) properties of Ga based monopnictides

    International Nuclear Information System (INIS)

    Varshney, Dinesh; Joshi, Geetanjali; Varshney, Meenu; Shriya, Swarna

    2010-01-01

    By formulating an effective interionic interaction potential that incorporates the long-range Coulomb, the covalency effects, the charge transfer caused by the deformation of the electron shells of the overlapping ions, the Hafemeister and Flygare type short-range overlap repulsion extended up to the second neighbour ions and the van der Waals (vdW) interaction, the pressure dependent elastic and thermodynamical properties of the III-V semiconductors as GaY (Y = N, P, As) are studied. The estimated values of phase transition pressure of GaY (Y = N, P, As) are in reasonably good agreement with the available data on the phase transition pressures (P t = 41, 22, 17 GPa). The vast volume discontinuity in pressure-volume phase diagram identifies a structural phase transition from zinc-blende (B3) to rock salt (B1) structure. Later on, the Poisson's ratio ν, the ratio R S/B of S (Voigt averaged shear modulus) over B (bulk modulus), elastic anisotropy parameter, elastic wave velocity, average wave velocity and Debye temperature as functions of pressure is calculated. From Poisson's ratio and the ratio R S/B it is inferred that GaY (Y = N, P, As) is brittle [ductile] in zinc-blende (B3) [Sodium Chloride (B1)] phase. To our knowledge this is the first quantitative theoretical prediction of the pressure dependence of ductile (brittle) nature of GaY compounds and still awaits experimental confirmations.

  18. Analytical determination of thiamine (vitamin B1) in irradiated and stored Brazilian beans

    International Nuclear Information System (INIS)

    Villavicencio, Anna L.C.H.; Mancini-Filho, Jorge; Bognar, A.

    1997-01-01

    Thiamine (vitamin B 1 ) content in two varieties of Brazilian beans, Phaselus vulgaris L., var. carioca and Vigna unguiculata (L) Walp, var. macacar , irradiated with doses ranging from 0,05, 1.0, 2.5, 5.0 and 10.0 kGy was investigated. After a 6 months storage period, the optimum cooking time was established for each dose and variety. Sensorial evaluation tests were carried out by a panel of six people trained to this specific task. Our purpose to work with these beans is because conflicting results have appeared in studies about vitamin loss after low-dose irradiation. In our case, after a 6-month storage period of this two kinds of beans, in addition to the analysis of cooking time and sensory properties the vitamin B 1 content was evaluated. No significant vitamin losses were observed in Macacar beans until 10.0 kGy. Carioca beans showed small losses after 2.5 kGy. (author). 23 refs., 2 figs., 5 tabs

  19. THE L1157-B1 ASTROCHEMICAL LABORATORY: MEASURING THE TRUE FORMALDEHYDE DEUTERATION ON GRAIN MANTLES

    International Nuclear Information System (INIS)

    Fontani, F.; Codella, C.; Ceccarelli, C.; Lefloch, B.; Viti, S.; Benedettini, M.

    2014-01-01

    L1157 is a prototypical chemically active outflow driven by a low-mass class-0 protostar, and B1 is its brightest bow shock. Toward L1157-B1, several emission lines of deuterated molecules have been detected for the first time by Codella et al. The authors suggested that these were formed on grain mantles, and then released into the gas phase by the passage of the shock. In this Letter we report observations obtained at high angular resolution with the Plateau de Bure Interferometer of HDCO and CH 2 DOH. The emission of HDCO perfectly delineates the region of the interface between the fast jet and the slower ambient material, confirming the predictions of the previous work that deuterated species were formed on grain mantles and then released into the gas phase by the passage of the shock. CH 2 DOH emission is fainter and thus its emitting region is not well determined. The deuterated fraction HDCO/H 2 CO is ∼0.1 in the HDCO emitting region, an order of magnitude larger than the upper limit found in the surrounding material, probably dominated by warm-gas chemistry and less affected by grain evaporation. Our study represents the first clear evidence ever found of a deuterated molecule as shock tracer, and yields an indirect but ''clean'' measurement of the deuteration of the ices covering the dust grains during the cold pre-protostellar phase

  20. Measurement and assessment of aflatoxin B1 and its producing molds in Iranian sausages and burgers

    Directory of Open Access Journals (Sweden)

    Siavash Maktabi

    2016-09-01

    Full Text Available Abstract Introduction: Aflatoxin B1 (AFB1 is one of the most well-known hepatocarcinogens in humans. Contamination of raw materials, used in the production of sausages and burgers, with aflatoxin producing molds can lead to increased level of aflatoxin in the final products and can impose hazards to human health. Unfortunately, aflatoxin is resistant to heating and freezing processes, etc. and can remain in these products untile consumption. Methods: During a six-month period, 45 sausage and 53 burger samples from valid brands across the country were randomly purchased from the stores. The samples were analyzed for AFB1 by ELISA technique. Meanwhile, the number of molds was calculated and aflatoxin producing molds were identified by direct and slide culture methods. Results: The findings showed that 2 susage samples (4.9% and 3 burger samples (6.3% were contaminated with >1 ng/g aflatoxin. Moreover, 4 burger samples (8.9% contaminated with mold included aspergillus flavus, aspergillus niger, mucor, and penicillium while, none of the susage samples showed mold contamination. Conclusion: The Iranian meat products had a relative aflatoxin B1 contamination during the study period, but the contamination rate was low and in allowable range. Standard hygienic preparation and packaging of meat products molds is recommended to reduce fungal contamination, especially aflatoxin-producing molds.