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Sample records for congenic normal mice

  1. CD8+ T cells are crucial for the ability of congenic normal mice to reject highly immunogenic sarcomas induced in nude mice with 3-methylcholanthrene

    DEFF Research Database (Denmark)

    Boesen, M; Svane, I M; Engel, A M;

    2000-01-01

    An attempt was made to identify the selection pressures put upon a growing tumour by CD8+ T cells. To this end tumours induced with 3-methylcholanthrene in T cell-deficient nude mice and in congenic T cell-competent nu/+ mice were transplanted to nu/+ recipients. The rejection rate of the sarcomas...

  2. Congenic mice: cutting tools for complex immune disorders.

    Science.gov (United States)

    Rogner, Ute C; Avner, Philip

    2003-03-01

    Autoimmune diseases are, in general, under complex genetic control and subject to strong interactions between genetics and the environment. Greater knowledge of the underlying genetics will provide immunologists with a framework for study of the immune dysregulation that occurs in such diseases. Ascertaining the number of genes that are involved and their characterization have, however, proven to be difficult. Improved methods of genetic analysis and the availability of a draft sequence of the complete mouse genome have markedly improved the outlook for such research, and they have emphasized the advantages of mice as a model system. In this review, we provide an overview of the genetic analysis of autoimmune diseases and of the crucial role of congenic and consomic mouse strains in such research.

  3. Very mild disease phenotype of congenic CftrTgH(neoimHgu cystic fibrosis mice

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    Leonhard-Marek Sabine

    2008-04-01

    Full Text Available Abstract Background A major boost to cystic fibrosis disease research was given by the generation of various mouse models using gene targeting in embryonal stem cells. Moreover, the introduction of the same mutation on different inbred strains generating congenic strains facilitated the search for modifier genes. From the original CftrTgH(neoimHgu mouse model with a divergent genetic background (129/Sv, C57BL/6, HsdOla:MF1 two inbred mutant mouse strains CF/1-CftrTgH(neoimHgu and CF/3-CftrTgH(neoimHgu had been generated using strict brother × sister mating. CF/1-CftrTgH(neoimHgu and CF/3-CftrTgH(neoimHgu mice were fertile and showed normal growth and lifespan. In this work the CftrTgH(neoimHgu insertional mutation was backcrossed from CF/3-CftrTgH(neoimHgu onto the inbred backgrounds C57BL/6J and DBA/2J generating congenic animals in order to clarify the differential impact of the Cftr mutation and the genetic background on the disease phenotype of the cystic fibrosis mutant mice. Clinical and electrophysiological features of the two congenic strains were compared with those of CF/1-CftrTgH(neoimHgu and CF/3-CftrTgH(neoimHgu and wild type controls. Results Under the standardized housing conditions of the animal facility, the four mouse strains CF/1-CftrTgH(neoimHgu, CF/3-CftrTgH(neoimHgu, D2.129P2(CF/3-CftrTgH(neoimHgu and B6.129P2(CF/3-CftrTgH(neoimHgu exhibited normal life expectancy. Growth of congenic cystic fibrosis mice was comparable with that of wild type controls. All mice but D2.129P2(CF/3-CftrTgH(neoimHgu females were fertile. Short circuit current measurements revealed characteristic response profiles of the HsdOla:MF1, DBA/2J and C57BL/6J backgrounds in nose, ileum and colon. All cystic fibrosis mouse lines showed the disease-typical hyperresponsiveness to amiloride in the respiratory epithelium. The mean chloride secretory responses to carbachol or forskolin were 15–100% of those of the cognate wild type control animals

  4. Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners in mice

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    Pacyniak, Erik [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Hagenbuch, Bruno [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); The University of Kansas Cancer Center, Kansas City, KS (United States); Klaassen, Curtis D. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Lehman-McKeeman, Lois [Bristol Myers Squibb Co., Princeton, NJ (United States); Guo, Grace L., E-mail: lguo@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2011-11-15

    BDE47, BDE99 and BDE153 are the predominant polybrominated diphenyl ether (PBDE) congeners detected in humans and can induce drug metabolizing enzymes in the liver. We have previously demonstrated that several human liver organic anion transporting polypeptides (humans: OATPs; rodents: Oatps) can transport PBDE congeners. Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. However, the mechanism of the hepatic PBDE uptake in mice is not known. Therefore, the purpose of the current study was to test the hypothesis that BDE47, BDE99, and BDE153 are substrates of mouse hepatic Oatps (Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1). We used Human Embryonic Kidney 293 (HEK293) cells transiently expressing individual Oatps and quantified the uptake of BDE47, BDE99, and BDE153. Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners, whereas Oatp1a1 did transport none. Kinetic studies demonstrated that Oatp1a4 and Oatp1b2 transported BDE47 with the greatest affinity, followed by BDE99 and BDE153. In contrast, Oatp2b1 transported all three PBDE congeners with similar affinities. The importance of hepatic Oatps for the liver accumulation of BDE47 was confirmed using Oatp1a4-, and Oatp1b2-null mice. -- Highlights: Black-Right-Pointing-Pointer PBDE congeners are substrates of OATPs expressed in human hepatocytes. Black-Right-Pointing-Pointer Mice are commonly used to study the toxicity of chemicals like the PBDE congeners. Black-Right-Pointing-Pointer Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE congeners in vitro. Black-Right-Pointing-Pointer In vivo Oatp1a4 plays a minor and Oatp1b2 a major role in BDE47 liver accumulation.

  5. Congenic mice reveal genetic epistasis and overlapping disease loci for autoimmune diabetes and listeriosis.

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    Wang, Nancy; Elso, Colleen M; Mackin, Leanne; Mannering, Stuart I; Strugnell, Richard A; Wijburg, Odilia L; Brodnicki, Thomas C

    2014-08-01

    The nonobese diabetic (NOD) mouse strain serves as a genomic standard for assessing how allelic variation for insulin-dependent diabetes (Idd) loci affects the development of autoimmune diabetes. We previously demonstrated that C57BL/6 (B6) mice harbor a more diabetogenic allele than NOD mice for the Idd14 locus when introduced onto the NOD genetic background. New congenic NOD mouse strains, harboring smaller B6-derived intervals on chromosome 13, now localize Idd14 to an ~18-Mb interval and reveal a new locus, Idd31. Notably, the B6 allele for Idd31 confers protection against diabetes, but only in the absence of the diabetogenic B6 allele for Idd14, indicating genetic epistasis between these two loci. Moreover, congenic mice that are more susceptible to diabetes are more resistant to Listeria monocytogenes infection. This result co-localizes Idd14 and Listr2, a resistance locus for listeriosis, to the same genomic interval and indicates that congenic NOD mice may also be useful for localizing resistance loci for infectious disease.

  6. Germ-line reinsertions of AKR murine leukemia virus genomes in Akv-1 congenic mice.

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    Rowe, W P; Kozak, C A

    1980-08-01

    Congenic mouse strains NIH,Akv-1 and NIH,Akv-2 carry the two high ecotropic virus-inducing loci of the AKR mouse on the NIH Swiss genetic background. Progeny tests of animals in three separate congenic families show that both Avk-1 and Akv-2 are stably transmitted as classical mendelian loci in these mice. However, during the process of inbreeding, additional chromosomal viral loci were detected in several NIH.Akv-1 sublines. These loci appeared only in the progeny of virus-positive females. They segregate with mendelian ratios, are unlinked to markers on chromsome 7 near Akv-1, and are phenotypically expressed as high-virus-inducing loci. The generation of new loci for viurs induction, no doubt resulting from the rare germ-line reintegration of the endogenous ectropic provirus, represents a unique form of gene duplication and rearrangement.

  7. Spontaneous metastasis in congenic mice with transgenic breast cancer is unaffected by plasminogen gene ablation

    DEFF Research Database (Denmark)

    Almholt, Kasper; Juncker-Jensen, Anna; Lærum, Ole Didrik;

    2013-01-01

    , suggesting that there is a functional redundancy with other proteases. To explore this functional overlap in the transgenic MMTV-PyMT breast cancer metastasis model, we have combined Plg deficiency and a pharmacological metalloprotease inhibitor, which is known to reduce metastasis in this model, and has...... been shown to synergistically inhibit other tissue remodeling events in Plg-deficient mice. While metalloprotease inhibition dramatically reduced metastasis, we found no effect of Plg deficiency on metastasis, either independently or in combination with metalloprotease inhibition. We further show...... that Plg gene deficiency is of no significant consequence in this metastasis model, when analyzed in two different congenic strains: the FVB strain, and a F1 hybrid of the FVB and C57BL/6J strains. We suggest that the extensive backcrossing performed prior to our studies has eliminated the confounding...

  8. Increased susceptibility to collagen-induced arthritis in female mice carrying congenic Cia40/Pregq2 fragments

    DEFF Research Database (Denmark)

    Liljander, Maria; Andersson, Åsa Inga Maria; Holmdahl, Rikard;

    2008-01-01

    of the B10.Q strain. The major polymorphic candidate genes for the effects on CIA are Cd79b, Abca8a, and Map2k6. The congenic fragment also contains polymorphic genes that affect reproductive behavior and reproductive success. The Sox9 gene, known to influence sex reversal, is a candidate gene...... with another locus, denoted Pregq2, known to affect reproductive success. The present study was performed to evaluate the role of the Cia40 locus in congenic B10.Q mice and to identify possible polymorphic candidate genes, which may also be relevant in the context of RA. METHODS: Congenic B10.Q mice carrying...... an NFR/N fragment surrounding the Cia40/Pregq2 loci were created by 10 generations of backcrossing (N10). The congenic mice were investigated in the CIA model, and the incidence and severity of arthritis as well as the serum levels of anti-collagen II (CII) antibodies were recorded. RESULTS: Significant...

  9. Expression of S100A8 correlates with inflammatory lung disease in congenic mice deficient of the cystic fibrosis transmembrane conductance regulator

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    Keet Mary

    2006-03-01

    Full Text Available Abstract Background Lung disease in cystic fibrosis (CF patients is dominated by chronic inflammation with an early and inappropriate influx of neutrophils causing airway destruction. Congenic C57BL/6 CF mice develop lung inflammatory disease similar to that of patients. In contrast, lungs of congenic BALB/c CF mice remain unaffected. The basis of the neutrophil influx to the airways of CF patients and C57BL/6 mice, and its precipitating factor(s (spontaneous or infection induced remains unclear. Methods The lungs of 20-day old congenic C57BL/6 (before any overt signs of inflammation and BALB/c CF mouse lines maintained in sterile environments were investigated for distinctions in the neutrophil chemokines S100A8 and S100A9 by quantitative RT-PCR and RNA in situ hybridization, that were then correlated to neutrophil numbers. Results The lungs of C57BL/6 CF mice had spontaneous and significant elevation of both neutrophil chemokines S100A8 and S100A9 and a corresponding increase in neutrophils, in the absence of detectable pathogens. In contrast, BALB/c CF mouse lungs maintained under identical conditions, had similar elevations of S100A9 expression and resident neutrophil numbers, but diverged in having normal levels of S100A8. Conclusion The results indicate early and spontaneous lung inflammation in CF mice, whose progression corresponds to increased expression of both S100A8 and S100A9, but not S100A9 alone. Moreover, since both C57BL/6 and BALB/c CF lungs were maintained under identical conditions and had similar elevations in S100A9 and neutrophils, the higher S100A8 expression in the former (or suppression in latter is a result of secondary genetic influences rather than environment or differential infection.

  10. Very mild disease phenotype of congenic CftrTgH(neoim)Hgu cystic fibrosis mice

    NARCIS (Netherlands)

    B. Tóth (Balázs); M. Wilke (Martina); F. Stanke (Frauke); M. Dorsch (Martina); S. Jansen (Silke); D. Wedekind (Dirk); N. Charizopoulou (Nikoletta); A.G. Bot (Alice); M. Burmester (Marion); S. Leonhard-Marek (Sabine); H.R. de Jonge (Hugo); H.J. Hedrich; G. Breves (Gerhard); B. Tümmler (Burkhard)

    2008-01-01

    textabstractBackground: A major boost to cystic fibrosis disease research was given by the generation of various mouse models using gene targeting in embryonal stem cells. Moreover, the introduction of the same mutation on different inbred strains generating congenic strains facilitated the search f

  11. Congenic mice provide evidence for a genetic locus that modulates spontaneous arthritis caused by deficiency of IL-1RA.

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    Yanhong Cao

    Full Text Available To understand the role of genetic factors involved in the development of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA, we have identified a genomic region containing a major quantitative trait locus (QTL for this disease. The QTL is on chromosome 1 and appears to be the strongest genetic region regulating arthritis. To confirm the importance of the QTL and to identify potential candidate genes within it, we conducted speed congenic breeding to transfer the QTL region from DBA/1 mice that are resistant to spontaneous arthritis into BALB/c(-/- which are susceptible. Genetic markers along every chromosome were used to assist in the selection of progeny in each generation to backcross to BALB/c(-/-. By the 6th generation we determined that all of the chromosomes in the progeny were of BALB/c origin with the exception of portions of chromosome 1. At this stage we intercrossed selected mice to produce homozygous strains containing the genomic background of BALB/c(-/- except for the QTL region on chromosome 1, which was from DBA/1. We were able to establish two congenic strains with overlapping DBA/1 DNA segments. These strains were observed for the development of spontaneous arthritis. Both congenic strains were relatively resistant to spontaneous arthritis and had delayed onset and reduced severity of disease. The gene/s that regulates this major QTL would appear to be located in the region of the QTL that is shared by both strains. The common transferred region is between D1Mit110 and D1Mit209 on chromosome 1. We evaluated this region for candidate genes and have identified a limited number of candidates. Confirmation of the identity and precise role of the candidates will require additional study.

  12. OXIDATION OF POLYCHLORINATED BIPHENYLS BY LIVER TISSUE SLICES FROM PHENOBARBITAL-PRETREATED MICE IS CONGENER-SPECIFIC AND ATROPSELECTIVE

    OpenAIRE

    Wu, Xianai; Duffel, Michael; Lehmler, Hans-Joachim

    2013-01-01

    Mouse models are powerful tools to study the developmental neurotoxicity of polychlorinated biphenyls (PCBs); however, studies of the oxidation of chiral PCB congeners to potentially neurotoxic hydroxylated metabolites (OH-PCBs) in mice have not been reported. Here we investigate the atropselective oxidation of chiral PCB 91 (2,2',3,4',6-pentachlorobiphenyl), PCB 95 (2,2',3,5',6-pentachlorobiphenyl), PCB 132 (2,2',3,3',4,6'-hexachlorobiphenyl), PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl) and ...

  13. IL-10 Production Is Critical for Sustaining the Expansion of CD5+ B and NKT Cells and Restraining Autoantibody Production in Congenic Lupus-Prone Mice.

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    Yuriy Baglaenko

    Full Text Available The development and progression of systemic lupus erythematosus is mediated by the complex interaction of genetic and environmental factors. To decipher the genetics that contribute to pathogenesis and the production of pathogenic autoantibodies, our lab has focused on the generation of congenic lupus-prone mice derived from the New Zealand Black (NZB strain. Previous work has shown that an NZB-derived chromosome 4 interval spanning 32 to 151 Mb led to expansion of CD5+ B and Natural Killer T (NKT cells, and could suppress autoimmunity when crossed with a lupus-prone mouse strain. Subsequently, it was shown that CD5+ B cells but not NKT cells derived from these mice could suppress the development of pro-inflammatory T cells. In this paper, we aimed to further resolve the genetics that leads to expansion of these two innate-like populations through the creation of additional sub-congenic mice and to characterize the role of IL-10 in the suppression of autoimmunity through the generation of IL-10 knockout mice. We show that expansion of CD5+ B cells and NKT cells localizes to a chromosome 4 interval spanning 91 to 123 Mb, which is distinct from the region that mediates the majority of the suppressive phenotype. We also demonstrate that IL-10 is critical to restraining autoantibody production and surprisingly plays a vital role in supporting the expansion of innate-like populations.

  14. Genetics of Bone Mineralization and Morphology in Inbred Mice: Analysis of the HcB/Dem Recombinant Congenic Strains

    Science.gov (United States)

    2005-04-01

    data for parameters with skewed distil- 3- PONT BEND MODULUS butions. Results of this analysis are summarized in Table 2. Ir TT . We used these data to...the pathogenesis of osteoporosis. I Bone Miner Res 9:739- [be murine strength is achieved. 743. 1002 YERSHOV ET AL. 16. Demant P, Hart AA 1986...Recombinant congenic strains--a 37. Linder E, Schork N 1994 Genetic dissection of complex traits. new tool for analyzing genetic traits determined by more than

  15. Insulin resistance, steatohepatitis, and hepatocellular carcinoma in a new congenic strain of Fatty Liver Shionogi (FLS) mice with the Lep(ob) gene.

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    Soga, Masahiko; Hashimoto, Setsuko; Kishimoto, Yoshio; Hirasawa, Tsutomu; Makino, Susumu; Inagaki, Shuichiro

    2010-01-01

    In order to examine the influence of obesity on metabolic disorder and liver pathogenesis of the Fatty Liver Shionogi (FLS) mouse, which develops hereditary fatty liver and spontaneous liver tumors, we established a new congenic strain named FLS-Lep(ob). The Lep(ob) gene of the C57BL/6JWakShi (B6)-Lep(ob)/Lep(ob) mouse was transferred into the genome of the FLS mouse, by backcross mating. FLS-Lep(ob)/Lep(ob) mice were maintained by intercrossing between Lep(ob)-heterozygous littermates. The FLS-Lep(ob)/Lep(ob) mice of both sexes developed remarkable hyperphagia, obesity and type 2 diabetes mellitus. At 12 weeks of age, glucosuria was detected in all male and female FLS-Lep(ob)/Lep(ob) mice. Biochemical examination demonstrated that the FLS-Lep(ob)/Lep(ob) mice have severe hyperlipidemia and hyperinsulinemia. The livers of FLS-Lep(ob)/Lep(ob) mice showed microvesicular steatosis and deposition of large lipid droplets in hepatocytes throughout the lobules. The steatohepatitis-like lesions including the multifocal mononuclear cell infiltration and clusters of foamy cells were observed earlier in FLS-Lep(ob)/ Lep(ob) mice than in FLS mice. B6-Lep(ob)/Lep(ob) mice did not show hepatic inflammatory change. Furthermore, FLS-Lep(ob)/Lep(ob) mice developed multiple hepatic tumors including hepatocellular adenomas and carcinomas following steatohepatitis. In conclusion, the FLS-Lep(ob)/Lep(ob) mice developed steatohepatitis and hepatic tumors following hepatic steatosis. The FLS-Lep(ob)/Lep(ob) mouse with obesity and type 2 diabetes mellitus might be a useful animal model for human non-alcoholic steatohepatitis (NASH).

  16. Exercise training modifies gut microbiota in normal and diabetic mice.

    Science.gov (United States)

    Lambert, Jennifer E; Myslicki, Jason P; Bomhof, Marc R; Belke, Darrell D; Shearer, Jane; Reimer, Raylene A

    2015-07-01

    Cecal microbiota from type 2 diabetic (db/db) and control (db/(+)) mice was obtained following 6 weeks of sedentary or exercise activity. qPCR analysis revealed a main effect of exercise, with greater abundance of select Firmicutes species and lower Bacteroides/Prevotella spp. in both normal and diabetic exercised mice compared with sedentary counterparts. Conversely, Bifidobacterium spp. was greater in exercised normal but not diabetic mice (exercise × diabetes interaction). How exercise influences gut microbiota requires further investigation.

  17. Identification of the Gasa3 and Gasa4 autoimmune gastritis susceptibility genes using congenic mice and partitioned, segregative and interaction analyses.

    Science.gov (United States)

    Silveira, P A; Wilson, W E; Esteban, L M; Jordan, M A; Hawke, C G; van Driel, I R; Baxter, A G

    2001-12-01

    BALB/c mice thymectomized on their third day of life develop a high incidence of experimental autoimmune gastritis (EAG) which closely resembles human chronic atrophic (type A, autoimmune) gastritis. Linkage analysis of (BALB/cCrSlcxC57BL/6)F2 mice previously demonstrated that the Gasa1 and Gasa2 genes on distal Chromosome (Chr) 4 have major effects on the development of EAG in this murine model, while other loci displayed a trend towards linkage. Here, we implemented partitioned chi(2)-analysis in order to develop a better understanding of the genotypes contributing to susceptibility and resistance at each linkage region. This approach revealed that linkage of Gasa1 and Gasa2 to EAG was due to codominant and recessive BALB/cCrSlc alleles, respectively. To identify additional EAG susceptibility genes, separate linkage studies were performed on Gasa1 heterozygotes and Gasa2 C57BL/6 homozygotes plus heterozygotes so as to minimize the effects of these disease genes. The enhanced sensitivity of these analyses confirmed the existence of a third EAG susceptibility gene (designated Gasa3) on Chr 6. Epistatic interactions between the Gasa2 EAG susceptibility gene and the H2 were also identified, and the presence of an H2-linked susceptibility gene (Gasa4) confirmed by analysis of H2 congenic mice.

  18. Congenic mice provide in vivo evidence for a genetic locus that modulates intrinsic transforming growth factor β1-mediated signaling and bone acquisition.

    Science.gov (United States)

    Mukherjee, Aditi; Larson, Emily A; Carlos, Amy S; Belknap, John K; Rotwein, Peter; Klein, Robert F

    2012-06-01

    Osteoporosis, the most common skeletal disorder, is characterized by low bone mineral density (BMD) and an increased risk of fragility fractures. BMD is the best clinical predictor of future osteoporotic fracture risk, but is a complex trait controlled by multiple environmental and genetic determinants with individually modest effects. Quantitative trait locus (QTL) mapping is a powerful method for identifying chromosomal regions encompassing genes involved in shaping complex phenotypes, such as BMD. Here we have applied QTL analysis to male and female genetically-heterogeneous F(2) mice derived from a cross between C57BL/6 and DBA/2 strains, and have identified 11 loci contributing to femoral BMD. Further analysis of a QTL on mouse chromosome 7 following the generation of reciprocal congenic strains has allowed us to determine that the high BMD trait, which tracks with the DBA/2 chromosome and exerts equivalent effects on male and female mice, is manifested by enhanced osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro and by increased growth of metatarsal bones in short-term primary culture. An insertion/deletion DNA polymorphism in Ltbp4 exon 12 that causes the in-frame removal of 12 codons in the DBA/2-derived gene maps within 0.6 Mb of the marker most tightly linked to the QTL. LTBP4, one of four paralogous mouse proteins that modify the bioavailability of the transforming growth factor β (TGF-β) family of growth factors, is expressed in differentiating MSC-derived osteoblasts and in long bones, and reduced responsiveness to TGF-β1 is observed in MSCs of mice homozygous for the DBA/2 chromosome 7. Taken together, our results identify a potential genetic and biochemical relationship between decreased TGF-β1-mediated signaling and enhanced femoral BMD that may be regulated by a variant LTBP4 molecule. Copyright © 2012 American Society for Bone and Mineral Research.

  19. Inhibitory effects of whisky congeners on IgE-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice.

    Science.gov (United States)

    Itoh, Tomohiro; Tsukane, Mariko; Koike, Minako; Nakamura, Chizu; Ohguchi, Kenji; Ito, Masafumi; Akao, Yukihiro; Koshimizu, Seiichi; Nozawa, Yoshinori; Wakimoto, Toshiyuki; Nukaya, Haruo; Suwa, Yoshihide

    2010-06-23

    Whisky is matured in oak casks. Many nonvolatile substances (whisky congeners, WC) seep from the oak cask during the maturing process. In this study, three antiallergic agents (syringaldehyde, SA; lyoniresinol, Lyo; and ellagic acid, EA) were isolated from WC. Treatment with SA, Lyo, and EA reduced the elevation of intracellular free Ca(2+) concentration ([Ca(2+)]i) and intracellular ROS production caused by FcepsilonRI activation. The inhibitions of the elevation of [Ca(2+)]i and intracellular ROS production by SA and Lyo were mainly due to the suppression of the NADPH oxidase activity and scavenging of the produced radical, respectively. On the other hand, EA inactivated spleen tyrosine kinase and led to the inhibition of the elevation of [Ca(2+)]i and intracellular ROS production. Furthermore, it was found that WC strongly inhibited IgE binding to the FcepsilonRIalpha chain, whereas SA, Lyo, and EA did not indicate this inhibitory effect. These results suggest that WC inhibits allergic reactions through multiple mechanisms. To disclose the in vivo effects of WC, SA, Lyo, and EA, these compounds were administered to type I allergic model mice, and the passive cutaneous anaphylaxis (PCA) reaction was measured. These compounds remarkably suppressed the PCA reaction. Taken together, these findings suggest that WC seemed to be beneficial to ameliorate allergic reactions.

  20. [Infection of Mice with Normal Immune Function by Taenia asiatica].

    Science.gov (United States)

    Liu, Xiao-yan; Guo, Guang-wu; Chen, Li-hong; Mo, Xing-ze; Yu, Yue-sheng

    2015-08-01

    The Taenia asiatica eggs pre-incubated with sodium hypochlorite solution for 4 min, 6 min and 8 mins were subcutaneously injected into mice with normal immune function(groups Al-A3 respectively, n=20 in each) and mice with immunosuppression (groups B1-B3, n=20 in each). All groups of mice began to show body discomfort on day 5 after infection and develop lumps on the back about on day 15. In groups Al-A3, animal death occurred during days 7-15, with a same survival rate of 95.0%(19/20) and infection rate of 89.4%(17/19), 73.6%(14/19) and 47.3%(9/19) respectively. In groups B1-B3, animal death occurred during days 7-50, with survival rate of 60%(13/20), 55%(11/20)and 55%(11/20) and infection rate of 76.9% (10/13), 54.5% (6/11) and 45.4% (5/11) respectively. After the scolex of cysticercus was evaginated with 15% pig bile, four suckers, an apparent rostellum and two distinct hook-like puncta structures were seen. These results indicate that mice with normal immune function can be used as a replacement of immunosuppressive mice to establish a T. asiatica oncosphere infection model. In addition, the T. asiatica eggs pre-incubated with sodium hypochlorite solution for 4 min have the strongest infection ability.

  1. Increased litter size and super-ovulation rate in congenic C57BL mice carrying a polymorphic fragment of NFR/N origin at the Fecq4 locus of chromosome 9

    DEFF Research Database (Denmark)

    Liljander, Maria; Andersson, Åsa Inga Maria; Holmdahl, Rikard

    2009-01-01

    By analysing N2 mice from a cross between the inbred C57BL strain B10.Q and the NMRI-related NFR/N strain, we recently identified a quantitative trait locus (QTL) influencing litter size. This locus is now denoted Fecq4, and it is present on the murine chromosome 9. In the present paper, we....... In addition, embryos containing the Fecq4 fragment were easy to cultivate in vitro, resulting in a higher yield of embryos reaching the blastocyst stage. We propose that B10.Q.NFR/N-Fecq4 congenic mice may be used to improve breeding or super-ovulation rate in different types of genetically modified mice (on...

  2. Normal cardiac function in mice with supraphysiological cardiac creatine levels.

    Science.gov (United States)

    Santacruz, Lucia; Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A; Jacobs, Danny O

    2014-02-01

    Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies.

  3. Very mild disease phenotype of congenic CftrTgH(neoim)Hgu cystic fibrosis mice

    OpenAIRE

    Leonhard-Marek Sabine; Burmester Marion; Bot Alice; Charizopoulou Nikoletta; Wedekind Dirk; Jansen Silke; Dorsch Martina; Stanke Frauke; Wilke Martina; Tóth Balázs (1985-); de Jonge Hugo R; Hedrich Hans-Jürgen; Breves Gerhard; Tümmler Burkhard

    2008-01-01

    Abstract Background A major boost to cystic fibrosis disease research was given by the generation of various mouse models using gene targeting in embryonal stem cells. Moreover, the introduction of the same mutation on different inbred strains generating congenic strains facilitated the search for modifier genes. From the original CftrTgH(neoim)Hgu mouse model with a divergent genetic background (129/Sv, C57BL/6, HsdOla:MF1) two inbred mutant mouse strains CF/1-CftrTgH(neoim)Hgu and CF/3-Cftr...

  4. Prepulse inhibition (PPI) of tactile startle response in recombinant congenic strains of mice:QTL mapping and comparison with acoustic PPI

    Institute of Scientific and Technical Information of China (English)

    Adam Torkamanzehi; Patricia Boksa; Ridha Joober

    2008-01-01

    Prepulse inhibition (PPI) of the startle response is a psychophysiological measure of sensorimotor gating believed to be cross-modal between different sensory systems.We analyzed the tactile startle response (TSR) and PPI of TSR (tPPD,using light as a prepulse stimulus,in the mouse strains A/J and C57BL/6J and 36 recombinant congenic strains derived from them.Parental strains were significantly different for TSR,but were comparable for tPPI.Among the congenic strains,variation for TSR was significant in both genetic backgrounds,but that of tPPI was significant only for the C57BL/6J background.Provisional mapping for loci modulating TSR and tPPI was carded out.Using mapping data from our previous study on acoustic startle responses (ASR) and PPI of ASR (aPPI),no common markers for aPPI and tPPI were identified.However,some markers were significantly associated with both ASR and TSIL at least in one genetic background.These results indicate cross-modal genetic regulation for the startle response but not for PPI,in these mouse strains.

  5. Acute Toxicities of the Saxitoxin Congeners Gonyautoxin 5, Gonyautoxin 6, Decarbamoyl Gonyautoxin 2&3, Decarbamoyl Neosaxitoxin, C-1&2 and C-3&4 to Mice by Various Routes of Administration

    Directory of Open Access Journals (Sweden)

    Andrew I. Selwood

    2017-02-01

    Full Text Available Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs. The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as “Toxicity Equivalence Factors” (TEFs. At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health.

  6. Acute Toxicities of the Saxitoxin Congeners Gonyautoxin 5, Gonyautoxin 6, Decarbamoyl Gonyautoxin 2&3, Decarbamoyl Neosaxitoxin, C-1&2 and C-3&4 to Mice by Various Routes of Administration.

    Science.gov (United States)

    Selwood, Andrew I; Waugh, Craig; Harwood, David T; Rhodes, Lesley L; Reeve, John; Sim, Jim; Munday, Rex

    2017-02-21

    Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as "Toxicity Equivalence Factors" (TEFs). At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health.

  7. ZPAC is required for normal spermatogenesis in mice.

    Science.gov (United States)

    Zuo, Er-Wei; Yang, Xiao-Gan; Lu, Yang-Qing; Xie, Long; Shang, Jiang-Hua; Li, Di; Yang, Huan; Hu, Lin-Lin; Zhao, Hui-Min; Lu, Sheng-Sheng; Lu, Ke-Huan

    2015-10-01

    The ubiquitin-proteasome pathway, involved in genetic recombination and sex-chromosome silencing during meiosis, plays critical roles in the specification of germ-line stem cells and the differentiation of gametes from gonocytes. Zygote-specific proteasome assembly chaperone (ZPAC) is expressed in the early mouse embryo, where it is important for progression of the mouse maternal-to-zygotic transition. The role of ZPAC during spermatogenesis in the adult gonads, however, remains unknown. In this study, rapid amplification of cDNA ends was used to determine the Zpac cDNA sequence, a 1584-bp transcript that includes a putative 1122-bp open reading frame coding for a 373 amino acid protein. Western blot and immunohistochemistry revealed that ZPAC was specifically expressed in gonads. To further dissect the function of ZPAC during spermatogenesis, we employed PiggyBac-based RNA interference vectors for transgenesis combined with cell transplantation to deplete Zpac during spermatogenesis. This RNAi-mediate depletion in Zpac expression disrupted normal spermatogenesis from spermatogonial stem cells. Two independent yeast two-hybrid screens further revealed an interaction between ZPAC and SYCE1. Together, these data suggest that ZPAC is required for normal spermatogenesis in mice.

  8. Adenylate kinase 1 knockout mice have normal thiamine triphosphate levels.

    Science.gov (United States)

    Makarchikov, Alexander F; Wins, Pierre; Janssen, Edwin; Wieringa, Bé; Grisar, Thierry; Bettendorff, Lucien

    2002-10-21

    Thiamine triphosphate (ThTP) is found at low concentrations in most animal tissues and it may act as a phosphate donor for the phosphorylation of proteins, suggesting a potential role in cell signaling. Two mechanisms have been proposed for the enzymatic synthesis of ThTP. A thiamine diphosphate (ThDP) kinase (ThDP+ATP if ThTP+ADP) has been purified from brewer's yeast and shown to exist in rat liver. However, other data suggest that, at least in skeletal muscle, adenylate kinase 1 (AK1) is responsible for ThTP synthesis. In this study, we show that AK1 knockout mice have normal ThTP levels in skeletal muscle, heart, brain, liver and kidney, demonstrating that AK1 is not responsible for ThTP synthesis in those tissues. We predict that the high ThTP content of particular tissues like the Electrophorus electricus electric organ, or pig and chicken skeletal muscle is more tightly correlated with high ThDP kinase activity or low soluble ThTPase activity than with non-stringent substrate specificity and high activity of adenylate kinase.

  9. Exhaled metallic mercury in acatalasemic, hypocatalasemic and normal mice injected with mercury (II chloride.

    Directory of Open Access Journals (Sweden)

    Meguro,Tadamichi

    1990-10-01

    Full Text Available To clarify the relationship between the catalase activity in mouse organs and the amounts of metallic mercury exhaled, normal, homozygous hypocatalasemic and acatalasemic mice were injected with mercuric chloride. The cumulative amount of metallic mercury exhaled by mice was evidently expressed in the descending order of acatalasemic, hypocatalasemic, and normal mice. Statistically significant differences in the cumulative exhaled metallic mercury levels were observed between acatalasemic and hypocatalasemic mice, between normal and hypocatalasemic mice, and between acatalasemic and normal mice using the method of one way analysis of variance (ANOVA. A linear relationship was obtained through logarithm of catalase activity in the lungs or the blood, and logarithm of the cumulative amount of the exhaled mercury.

  10. Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice

    OpenAIRE

    Takayanagi, Y.; Yoshida, M; Bielsky, IF; Ross, HE; Kawamata, M; Onaka, J; Yanagisawa, Teruyuki; Kimura, T.; Matzuk, MM; Young, LJ; Nishimori, K.

    2006-01-01

    The oxytocin receptor (OXTR) and its ligand, oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene (Oxtr-/-) and compared them with OXT-deficient (Oxt-/-) mice. Oxtr-/- mice were viable and had no obvious deficits in fertility or reproductive behavior. Oxtr-/- dams exhibited normal parturition but demonstrated defects in lactation and mater...

  11. Leg contracture in mice: an assay of normal tissue response

    Energy Technology Data Exchange (ETDEWEB)

    Stone, H.B.

    1984-07-01

    Leg contracture, defined as the difference in extensibility of the control and irradiated hind legs of mice, was found to correlate with single doses of radiation from about 20 to 80 Gy. The time of development of the early phase of the response coincided with that reported for the appearance of the acute skin response, and in some cases, partially reversed as this reaction healed. The contracture then progressed again at a moderate rate through 90 days, and then more slowly through one year. Skin contraction, measured by decrease in intertattoo distance, was assayed in the same mice. It followed the same time course as leg contracture, but had a different dose-response relationship. To determine the contribution of skin contraction to the overall leg contracture response, mice were sacrificed and the leg contracture measured before and after the removal of the skin of the leg. After doses of up to 30 Gy, little contracture remained from skinning the leg, indicating that skin contraction was largely responsible for leg contracture in this dose range. After doses of about 45 Gy and above, some contracture remained in the skinned legs, although less than in intact legs. There was little or no enhancement of either skin contraction or leg contracture by the hypoxic cell sensitizers metronidazole or misonidazole.

  12. Characterization of colonic dendritic cells in normal and colitic mice

    Institute of Scientific and Technical Information of China (English)

    Sheena M Cruickshank; Nicholas R English; Peter J Felsburg; Simon R Carding

    2005-01-01

    AIM: Recent studies demonstrating the direct involvement of dendritic cells (DC) in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC.METHODS: Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient (IL2-/-) mice that develop colitis.RESULTS: In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type 1 myeloid (CD11c+, CD11b+,B220-, CD8α-) DC made up the largest (40-45%) population and all DC expressed low levels of CD80, CD86, and CD40,and had high endocytic activity consistent with an immature phenotype. In colitic IL2-/- mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes (MLN).The majority (>85%) of DC in the colon and MLN of IL2-/-mice were type 1 myeloid, and expressed high levels of MHC class Ⅱ, CD80, CD86, CD 40, DEC 205, and CCR5molecules and were of low endocytic activity consistent with mature DC.CONCLUSION: These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon.

  13. Dynamics of testicular germ cell apoptosis in normal mice and transgenic mice overexpressing rat androgen-binding protein

    Directory of Open Access Journals (Sweden)

    Petrusz Peter

    2003-06-01

    Full Text Available Abstract The number and type of testicular germ cells undergoing apoptosis in different age groups of mice (from 7 to 360 days of age was determined and compared in age-matched wild type (WT control and in a transgenic (TG mice homozygous to rat androgen binding protein (ABP using flow cytometry. Flow cytometric quantification revealed that the total number of germ cells undergoing apoptosis did not differ significantly in WT and TG mice up to Day 14. From Day 21 to Day 60, the number of germ cells undergoing apoptosis was consistently higher in TG than in WT mice. Starting from Day 90, the number of germ cells undergoing apoptosis in TG mice was lower than controls until Day 360. In 21–60 days old TG mice, spermatogonia, S-Phase cells, and primary spermatocytes are the cell types undergoing apoptosis at significantly greater numbers than those in WT mice. However, starting from day 60, the total number of spermatids undergoing apoptosis was significantly lower in TG mice than in age-matched WT controls. TdT-mediated dUTP-biotin nick end labeling (TUNEL in testicular sections from TG mice of 21 and 30 days of age confirmed the presence of increased numbers of apoptotic germ cells compared to their age matched controls. These data indicate that the continuous presence of greater than physiological concentrations of ABP in the mouse testis has a biphasic effect on the frequency of apoptosis in germ cells. The initial pre-pubertal increase in testicular germ cell apoptosis may result from direct or indirect actions of ABP and is likely to determine the subsequent life-death balance of germ cell populations in TG mice, whereas the subsequent reduction may result from maturation depletion. A wave of apoptosis during the pre-pubertal period is required for normal spermatogenesis to develop, and our data indicate that this apoptotic wave may be regulated by ABP and/or androgens.

  14. Selective radioprotection of normal tissues by bowman-birk proteinase inhibitor (BBI) in mice

    Energy Technology Data Exchange (ETDEWEB)

    Dittmann, K.; Toulany, M.; Peter Rodemann, H. [Div. of Radiobiology and Environmental Research, Dept. of Radiation Oncology, Univ. of Tuebingen (Germany); Classen, J.; Heinrich, V. [Dept. of Radiation Oncology, Univ. of Tuebingen (Germany); Milas, L. [Dept. of Experimental Radiation Oncology, The Univ. of Texas, M.D. Anderson Cancer Center, Houston, TX (United States)

    2005-03-01

    Background and purpose: the efficacy of radiotherapy is limited by the response of normal tissues within the radiation field. The application of normal-tissue-specific radioprotectors may improve the therapeutic benefit of radiotherapy. The purpose of the present study was to explore the in vivo normal-tissue radioprotective potential of Bowman-Birk proteinase inhibitor (BBI), which acts as a normal-cell-specific radioprotector in vitro. Material and methods: the leg contracture assay in mice, a model system assessing radiation-induced fibrotic processes, was used. To determine whether BBI acts also as a radioprotector of tumors (i.e., FSA and FSAII), the tumor growth delay assay was used. Results: radiation induced leg contracture in mice with a maximum of about 8 mm at day 150 after irradiation. Treatment of mice with 100 mg/kg BBI before irradiation reduced leg contracture by > 4 mm, by about 50% (p < 0.05, t-test). Doses < 100 mg/kg were ineffective, and doses > 100 mg/kg did not further increase the degree of radioprotection. By contrast, BBI did not induce radioprotection of either TP53-mutated FSA or TP53-normal FSAII tumor xenografts in mice, which argues for normal-tissue-specific effect. Conclusion: BBI acts as a potent selective normal-tissue radioprotector in vitro and in vivo, apparently without protecting tumors, and thus has the potential to improve clinical radiotherapy. (orig.)

  15. Relationships between protein and mineral during enamel development in normal and genetically altered mice

    Science.gov (United States)

    Smith, Charles E.; Hu, Yuanyuan; Richardson, Amelia S.; Bartlett, John D.; Hu, Jan C-C.; Simmer, James P.

    2012-01-01

    The purpose of this study was to quantify and compare the amounts of volatiles (mostly protein) and mineral present in developing incisor enamel in normal mice and in those genetically engineered for absence of intact enamelin, ameloblastin, matrix metalloproteinase 20 (MMP20) or kallikrein-related peptidase 4 (KLK4). Data indicated that all mice showed peaks in the gross weight of volatiles and a similar weight of mineral at locations on incisors normally associated with early maturation. Thereafter, the content of volatiles on normal incisors declined rapidly by as much as 62%, but not by 100%, over 2 mm, accompanied by increases of ~threefold in mineral weights. Enamelin heterozygous mice (lower incisors) showed a decrease in volatile content across the maturation stage, yet mineral failed to increase significantly. Mmp20 null mice showed no significant loss of volatiles from maturing enamel, yet the amount of mineral increased. Klk4 null mice showed normal mineral acquisition up to early maturation, but the input of new volatiles in mid to late maturation caused the final mineralization to slow below normal levels. These results suggest that it is not only the amount of protein but also the nature or type of protein or fragments present in the local crystallite environment that affects their volumetric expansion as they mature. PMID:22243238

  16. Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice.

    Science.gov (United States)

    Murphy, Andrew J; Macdonald, Lynn E; Stevens, Sean; Karow, Margaret; Dore, Anthony T; Pobursky, Kevin; Huang, Tammy T; Poueymirou, William T; Esau, Lakeisha; Meola, Melissa; Mikulka, Warren; Krueger, Pamela; Fairhurst, Jeanette; Valenzuela, David M; Papadopoulos, Nicholas; Yancopoulos, George D

    2014-04-01

    Mice genetically engineered to be humanized for their Ig genes allow for human antibody responses within a mouse background (HumAb mice), providing a valuable platform for the generation of fully human therapeutic antibodies. Unfortunately, existing HumAb mice do not have fully functional immune systems, perhaps because of the manner in which their genetic humanization was carried out. Heretofore, HumAb mice have been generated by disrupting the endogenous mouse Ig genes and simultaneously introducing human Ig transgenes at a different and random location; KO-plus-transgenic humanization. As we describe in the companion paper, we attempted to make mice that more efficiently use human variable region segments in their humoral responses by precisely replacing 6 Mb of mouse Ig heavy and kappa light variable region germ-line gene segments with their human counterparts while leaving the mouse constant regions intact, using a unique in situ humanization approach. We reasoned the introduced human variable region gene segments would function indistinguishably in their new genetic location, whereas the retained mouse constant regions would allow for optimal interactions and selection of the resulting antibodies within the mouse environment. We show that these mice, termed VelocImmune mice because they were generated using VelociGene technology, efficiently produce human:mouse hybrid antibodies (that are rapidly convertible to fully human antibodies) and have fully functional humoral immune systems indistinguishable from those of WT mice. The efficiency of the VelocImmune approach is confirmed by the rapid progression of 10 different fully human antibodies into human clinical trials.

  17. Glucocorticoid receptor deficient thymic and peripheral T cells develop normally in adult mice.

    Science.gov (United States)

    Purton, Jared F; Zhan, Yifan; Liddicoat, Douglas R; Hardy, Charles L; Lew, Andrew M; Cole, Timothy J; Godfrey, Dale I

    2002-12-01

    The involvement of glucocorticoid receptor (GR) signaling in T cell development is highly controversial, with several studies for and against. We have previously demonstrated that GR(-/-) mice, which usually die at birth because of impaired lung development, exhibit normal T cell development, at least in embryonic mice and in fetal thymus organ cultures. To directly investigate the role of GR signaling in adult T cell development, we analyzed the few GR(-/-) mice that occasionally survive birth, and irradiated mice reconstituted with GR(-/-) fetal liver precursors. All thymic and peripheral T cells, as well as other leukocyte lineages, developed and were maintained at normal levels. Anti-CD3-induced cell death of thymocytes in vitro, T cell repertoire heterogeneity and T cell proliferation in response to anti-CD3 stimulation were normal in the absence of GR signaling. Finally, we show that metyrapone, an inhibitor of glucocorticoid synthesis (commonly used to demonstrate a role for glucocorticoids in T cell development), impaired thymocyte development regardless of GR genotype indicating that this reagent inhibits thymocyte development in a glucocorticoid-independent fashion. These data demonstrate that GR signaling is not required for either normal T cell development or peripheral maintenance in embryonic or adult mice.

  18. No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions

    DEFF Research Database (Denmark)

    Wellendorph, Petrine; Johansen, Lars Dan; Jensen, Anders Asbjørn;

    2009-01-01

    . Analogously to the closely related calcium-sensing receptor, GPRC6A has been proposed to function as a metabolic sensor of Ca2+ and amino acids in bone and other tissues. In the present study, we have generated the first GPRC6A knockout mice and studied their phenotype with particular focus on bone...... homeostasis. The generated GPRC6A knockout mice are viable and fertile, develop normally and exhibit no significant differences in body weight compared to wild type littermates. Assessment of bone mineral density, histomorphometry and bone metabolism demonstrated no significant differences between 13-week......-old knockout and wild type mice. In conclusion, our data do not support a role for GPRC6A in normal bone physiology....

  19. Kinetics of small lymphocytes in normal and nude mice after splenectomy

    DEFF Research Database (Denmark)

    Hougen, H P; Hansen, F; Jensen, E K

    1977-01-01

    Autoradiography and various quantitations on lymphoid tissues have been used to evaluate the kinetics of small lymphocytes in normal (+/nu or +/+) and congenitally athymic nude (nu/nu) NMRI mice 1 month after splenectomy or sham-splenectomy. The results indicate that splenectomy causes depressed...

  20. Antidiabetic activity of Plumeria rubra L. in normal and alloxan induced diabetic mice

    Directory of Open Access Journals (Sweden)

    Amruta V. Yadav

    2016-06-01

    Conclusions: PR exhibited significant antihyperglycemic activity in normal and alloxan-induced diabetic mice. The results of the present study provide support to the traditional usage of the plant in diabetes. [Int J Basic Clin Pharmacol 2016; 5(3.000: 884-889

  1. A lifespan MRI evaluation of ventricular enlargement in normal aging mice.

    Science.gov (United States)

    Chen, Chiao-Chi V; Tung, Yu-Ying; Chang, Chen

    2011-12-01

    Ventricular enlargement has been proposed as a structural biomarker for the progression of Alzheimer's disease (AD). This biomarker, established in human patients, needs to be translated to animals to facilitate drug development for the disease. However, ventricular enlargement is not exclusive to AD, since the ventricle size increases during normal aging. A longitudinal characterization of ventricular enlargement in normal aging in mice is therefore crucial before further evaluations of mouse models or neurodegenerative diseases associated to brain atrophy. To this end, ventricular enlargement in normal aging mice was characterized over the lifespan (i.e., 2 years). The results showed that the overall ventricle size increased with age, with the expansion beginning during the early life stages and continuing to old age. The reported data represent a biomarker benchmark for normal aging mice under unmodified conditions. This provides a foundation for evaluating the validity of AD mouse models or the effects of potential drugs. The considerable physiological ventricular enlargement during normal aging must be considered in related experiments.

  2. Construction of a hepatic stellate cells subtracted cDNA library of differentially expressed genes in normal mice and mice with Schistosomiasis japonica*

    OpenAIRE

    2005-01-01

    To construct a hepatic stellate cells (HSCs) subtracted cDNA library to find differentially expressed genes in normal mice and mice infected with Schistosoma japonicum (S. japonicum). Suppression subtractive hybridization (SSH) was used. The cDNA fragments of normal mouse were compared to those of schistosoma-infected mice to find differentially expressed genes. Then differentially expressed cDNA fragments were directly inserted into T/A cloning vector to set up the subtractive library. Ampli...

  3. Complexin 1 knockout mice exhibit marked deficits in social behaviours but appear to be cognitively normal.

    Science.gov (United States)

    Drew, Cheney J G; Kyd, Rachel J; Morton, A Jennifer

    2007-10-01

    Complexins are presynaptic proteins that modulate neurotransmitter release. Abnormal expression of complexin 1 (Cplx1) is seen in several neurodegenerative and psychiatric disorders in which disturbed social behaviour is commonplace. These include Parkinsons's disease, Alzheimer's disease, schizophrenia, major depressive illness and bipolar disorder. We wondered whether changes in Cplx1 expression contribute to the psychiatric components of the diseases in which Cplx1 is dysregulated. To investigate this, we examined the cognitive and social behaviours of complexin 1 knockout mice (Cplx1(-/-)) mice. Cplx1(-/-) mice have a profound ataxia that limits their ability to perform co-ordinated motor tasks. Nevertheless, when we taught juvenile Cplx1(-/-) mice to swim, they showed no evidence of cognitive impairment in the two-choice swim tank. In contrast, although olfactory discrimination in Cplx1(-/-) mice was normal, Cplx1(-/-) mice failed in the social transmission of food preference task, another cognitive paradigm. This was due to abnormal social interactions rather than cognitive impairments, increased anxiety or neophobia. When we tested social behaviour directly, Cplx1(-/-) mice failed to demonstrate a preference for social novelty. Further, in a resident-intruder paradigm, male Cplx1(-/-) mice failed to show the aggressive behaviour that is typical of wild-type males towards an intruder mouse. Together our results show that in addition to the severe motor and exploratory deficits already described, Cplx1(-/-) mice have pronounced deficits in social behaviours. Abnormalities in complexin 1 levels in the brain may therefore contribute to the psycho-social aspects of human diseases in which this protein is dysregulated.

  4. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

    Science.gov (United States)

    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  5. Doublecortin knockout mice show normal hippocampal-dependent memory despite CA3 lamination defects.

    Directory of Open Access Journals (Sweden)

    Johanne Germain

    Full Text Available Mutations in the human X-linked doublecortin gene (DCX cause major neocortical disorganization associated with severe intellectual disability and intractable epilepsy. Although Dcx knockout (KO mice exhibit normal isocortical development and architecture, they show lamination defects of the hippocampal pyramidal cell layer largely restricted to the CA3 region. Dcx-KO mice also exhibit interneuron abnormalities. As well as the interest of testing their general neurocognitive profile, Dcx-KO mice also provide a relatively unique model to assess the effects of a disorganized CA3 region on learning and memory. Based on its prominent anatomical and physiological features, the CA3 region is believed to contribute to rapid encoding of novel information, formation and storage of arbitrary associations, novelty detection, and short-term memory. We report here that Dcx-KO adult males exhibit remarkably preserved hippocampal- and CA3-dependant cognitive processes using a large battery of classical hippocampus related tests such as the Barnes maze, contextual fear conditioning, paired associate learning and object recognition. In addition, we show that hippocampal adult neurogenesis, in terms of proliferation, survival and differentiation of granule cells, is also remarkably preserved in Dcx-KO mice. In contrast, following social deprivation, Dcx-KO mice exhibit impaired social interaction and reduced aggressive behaviors. In addition, Dcx-KO mice show reduced behavioral lateralization. The Dcx-KO model thus reinforces the association of neuropsychiatric behavioral impairments with mouse models of intellectual disability.

  6. Validation of Simple Sequence Length Polymorphism Regions of Commonly Used Mouse Strains for Marker Assisted Speed Congenics Screening

    Directory of Open Access Journals (Sweden)

    Channabasavaiah B. Gurumurthy

    2015-01-01

    Full Text Available Marker assisted speed congenics technique is commonly used to facilitate backcrossing of mouse strains in nearly half the time it normally takes otherwise. Traditionally, the technique is performed by analyzing PCR amplified regions of simple sequence length polymorphism (SSLP markers between the recipient and donor strains: offspring with the highest number of markers showing the recipient genome across all chromosomes is chosen for the next generation. Although there are well-defined panels of SSLP makers established between certain pairs of mice strains, they are incomplete for most strains. The availability of well-established marker sets for speed congenic screens would enable the scientific community to transfer mutations across strain backgrounds. In this study, we tested the suitability of over 400 SSLP marker sets among 10 mouse strains commonly used for generating genetically engineered models. The panel of markers presented here can readily identify the specified strains and will be quite useful in marker assisted speed congenic screens. Moreover, unlike newer single nucleotide polymorphism (SNP array methods which require sophisticated equipment, the SSLP markers panel described here only uses PCR and agarose gel electrophoresis of amplified products; therefore it can be performed in most research laboratories.

  7. Mice deficient in 11beta-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation

    DEFF Research Database (Denmark)

    Justesen, Jeannette; Mosekilde, Lis; Holmes, Megan

    2004-01-01

    and regenerates active cortisol (corticosterone) from circulating inert 11-keto forms. The aim of the present study was to investigate the role of this intracrine activation of GCs on normal bone physiology in vivo using mice deficient in 11betaHSD1 (HSD1(-/-)). The HSD1(-/-) mice exhibited no significant changes...... in cortical or trabecular bone mass compared with wild-type (Wt) mice. Aged HSD1(-/-) mice showed age-related bone loss similar to that observed in Wt mice. Histomorphometric analysis showed similar bone formation and bone resorption parameters in HSD1(-/-) and Wt mice. However, examination of bone marrow...

  8. Radioiodinated Naphthylalanine Derivatives Targeting Pancreatic Beta Cells in Normal and Nonobese Diabetic Mice

    Science.gov (United States)

    Amartey, John K.; Shi, Yufei; Al-Jammaz, Ibrahim; Esguerra, Celestina; Al-Otaibi, Basem; Al-Mohanna, Futwan

    2008-01-01

    An imaging method capable of using a signal from pancreatic beta cells to determine their mass would be of immense value in monitoring the progression of diabetes as well as response to treatment. Somatostatin receptors (SSTRs) are expressed on beta cells and are a potential target for imaging. The main objective of this study was to investigate whether pancreatic beta cells are a target for radiolabeled naphthylalanine derivatives. The molecules were subjected to in vitro and ex vivo evaluations. Pancreatic uptake of radioactivity was lower in nonobese diabetic (NOD) mice than normal mice at all time points investigated (P < .05) and correlated with the number of islets in tissue sections of both control and NOD mice. Immunohistochemical and confocal fluorescent microscopic studies showed colocalization of insulin and the conjugate radioligand in the pancreas. The results demonstrated that pancreatic uptake is receptor-mediated, and that beta cells are the primary target. PMID:18483609

  9. Neonatal iron deficiency causes abnormal phosphate metabolism by elevating FGF23 in normal and ADHR mice.

    Science.gov (United States)

    Clinkenbeard, Erica L; Farrow, Emily G; Summers, Lelia J; Cass, Taryn A; Roberts, Jessica L; Bayt, Christine A; Lahm, Tim; Albrecht, Marjorie; Allen, Matthew R; Peacock, Munro; White, Kenneth E

    2014-02-01

    Fibroblast growth factor 23 (FGF23) gain of function mutations can lead to autosomal dominant hypophosphatemic rickets (ADHR) disease onset at birth, or delayed onset following puberty or pregnancy. We previously demonstrated that the combination of iron deficiency and a knock-in R176Q FGF23 mutation in mature mice induced FGF23 expression and hypophosphatemia that paralleled the late-onset ADHR phenotype. Because anemia in pregnancy and in premature infants is common, the goal of this study was to test whether iron deficiency alters phosphate handling in neonatal life. Wild-type (WT) and ADHR female breeder mice were provided control or iron-deficient diets during pregnancy and nursing. Iron-deficient breeders were also made iron replete. Iron-deficient WT and ADHR pups were hypophosphatemic, with ADHR pups having significantly lower serum phosphate (p 50 fold; p < 0.01). WT and ADHR pups receiving low iron had elevated intact serum FGF23; ADHR mice were affected to a greater degree (p < 0.01). Iron-deficient mice also showed increased Cyp24a1 and reduced Cyp27b1, and low serum 1,25-dihydroxyvitamin D (1,25D). Iron repletion normalized most abnormalities. Because iron deficiency can induce tissue hypoxia, oxygen deprivation was tested as a regulator of FGF23, and was shown to stimulate FGF23 mRNA in vitro and serum C-terminal FGF23 in normal rats in vivo. These studies demonstrate that FGF23 is modulated by iron status in young WT and ADHR mice and that hypoxia independently controls FGF23 expression in situations of normal iron. Therefore, disturbed iron and oxygen metabolism in neonatal life may have important effects on skeletal function and structure through FGF23 activity on phosphate regulation.

  10. Impairing effects of angiotensin-converting enzyme inhibitor Captopril on bone of normal mice.

    Science.gov (United States)

    Yang, Min; Xia, Chao; Song, Yan; Zhao, Xi; Wong, Man-Sau; Zhang, Yan

    2016-01-15

    There are contradicting results about the effects of angiotensin-converting enzyme inhibitors (ACEIs) on bones. This study was aimed to investigate the effect of ACEI, Captopril, on bone metabolism and histology as well as the action of Captopril on skeletal renin-angiotensin system (RAS) and bradykinin receptor pathway in normal male mice. The urine, serum, tibias and femurs from normal control mice and Captopril-treated (10mg/kg) mice were collected for biochemical, histological and molecular analyses after drug administration for eight weeks. The mice after the treatment with Captopril had a significant decrease of serum testosterone level. The histological measurements showed the loss of trabecular bone mass and trabecular bone number, and the breakage of trabecular bone network as well as the changes of chondrocyte zone at epiphyseal plate in Captopril-treated mice. The defect of Captopril on trabecular bone was reflected by the quantitative bio-parameters from micro-CT. The expression of renin receptor and bradykinin B2 receptor (B2R) was significantly up-regulated in tibia of mice upon to the Captopril treatment, which decreased the ratio of OPG/RANKL and the expression of osteoblastic factor RUNX2. Furthermore, Captopril treatment resulted in the increase of pAkt/Akt and pNFκB expression in tibia. The present study revealed the impairing effects of Captopril on bone via interfering with the circulating sex hormone level and B2R pathway, which suggests that the bone metabolism of patients need to be carefully monitored when being prescribed for ACEIs. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Kinetics of small lymphocytes in normal and nude mice after splenectomy

    DEFF Research Database (Denmark)

    Hougen, H P; Hansen, F; Jensen, E K;

    1977-01-01

    Autoradiography and various quantitations on lymphoid tissues have been used to evaluate the kinetics of small lymphocytes in normal (+/nu or +/+) and congenitally athymic nude (nu/nu) NMRI mice 1 month after splenectomy or sham-splenectomy. The results indicate that splenectomy causes depressed ......, are released from the lympho-myeloid organs in compensation for the loss of long-lived, thymus-derived cells....

  12. Regional Heterogeneity in Murine Lung Fibroblasts from Normal Mice or Mice Exposed Once to Cigarette Smoke

    Science.gov (United States)

    Preobrazhenska, Olena; Wright, Joanne L.; Churg, Andrew

    2012-01-01

    Chronic obstructive lung disease (COPD) is characterized by matrix deposition in the small airways but matrix loss from the parenchyma, phenomena which must depend on the ability of local fibroblasts to produce matrix after smoke exposure. To investigate this idea, we exposed C57Bl/6 mice once to cigarette smoke or to air (control) and prepared primary cultures of lung fibroblasts by microdissecting large airways (trachea, LAF), medium size airways (major bronchi, MAF) and parenchyma (PF). Control PF showed the lowest rate of wound closure and wound closure was depressed in all lines by a single in vivo smoke exposure. Gene expression of matrix proteins differed considerably among the sites; decorin, which may sequester TGFβ, was markedly higher in PF. PF showed higher intrinsic ratios of pSmad2/Smad2. Smoke caused much greater increases in secreted and matrix deposited collagens 1 and 3 in PF than in LAF or MAF. Expression of Thy-1, a gene that suppresses myofibroblast differentiation, was increased by smoke in PF. We conclude that there is considerable regional heterogeneity in murine lung fibroblasts in terms of matrix production, either basally or after in vivo smoke exposure; that PF have lower ability to repair wounds and higher intrinsic TGFβ signaling; and that a single exposure to smoke produces lasting changes in the pattern of matrix production and wound repair, changes that may be mediated in part by smoke-induced release of TGFβ. However, PF still retain the ability to repair by producing new matrix after a single in vivo smoke exposure. PMID:22761892

  13. Comparative analysis of gastrointestinal microbiota between normal and caudal-related homeobox 2 (cdx2) transgenic mice.

    Science.gov (United States)

    Sakamoto, Hirotsugu; Asahara, Takashi; Chonan, Osamu; Yuki, Norikatsu; Mutoh, Hiroyuki; Hayashi, Shunji; Yamamoto, Hironori; Sugano, Kentaro

    2015-01-01

    Caudal-related homeobox 2 (Cdx2) is expressed in the human intestinal metaplastic mucosa and induces intestinal metaplastic mucosa in the Cdx2 transgenic mouse stomach. Atrophic gastritis and intestinal metaplasia commonly lead to gastric achlorhydria, which predisposes the stomach to bacterial overgrowth. In the present study, we determined the differences in gut microbiota between normal and Cdx2 transgenic mice, using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Twelve normal (control) and 12 Cdx2 transgenic mice were sacrificed, and the gastric, jejunal, ileac, cecal and colonic mucosa, and feces were collected. To quantitate bacterial microbiota, we used real-time qRTPCR with 16S rRNA gene-targeted, species-specific primers. The total numbers of bacteria in the gastric, jejunal, ileac, cecal, and colonic mucosa of the Cdx2 transgenic mice were significantly higher than those of the normal mice. The Bacteroides fragilis group and also Prevotella were not detected in the stomach of the normal mice, although they were detected in the Cdx2 transgenic mice. Moreover, the Clostridium coccoides group, Clostridium leptum subgroup, Bacteroides fragilis group, and Prevotella were not detected in the jejunum or ileum of the normal mice, although they were detected in the Cdx2 transgenic mice. The fecal microbiota of the normal mice was similar to that of the Cdx2 transgenic mice. Our results showed the differences in composition of gut microbiota between normal and Cdx2 transgenic mice, which may be caused by the development of gastric achlorhydria and intestinal metaplasia in Cdx2 transgenic mice.

  14. The cell adhesion molecule nectin-1 is critical for normal enamel formation in mice.

    Science.gov (United States)

    Barron, Martin J; Brookes, Steven J; Draper, Clare E; Garrod, David; Kirkham, Jennifer; Shore, Roger C; Dixon, Michael J

    2008-11-15

    Nectin-1 is a member of a sub-family of immunoglobulin-like adhesion molecules and a component of adherens junctions. In the current study, we have shown that mice lacking nectin-1 exhibit defective enamel formation in their incisor teeth. Although the incisors of nectin-1-null mice were hypomineralized, the protein composition of the enamel matrix was unaltered. While strong immunostaining for nectin-1 was observed at the interface between the maturation-stage ameloblasts and the underlying cells of the stratum intermedium (SI), its absence in nectin-1-null mice correlated with separation of the cell layers at this interface. Numerous, large desmosomes were present at this interface in wild-type mice; however, where adhesion persisted in the mutant mice, the desmosomes were smaller and less numerous. Nectins have been shown to regulate tight junction formation; however, this is the first report showing that they may also participate in the regulation of desmosome assembly. Importantly, our results show that integrity of the SI-ameloblast interface is essential for normal enamel mineralization.

  15. Rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Afifi, M.S.H.

    1985-01-01

    The objective of this study was to investigate the mechanisms of rejection of normal and neoplastic hemopoietic cells by lethally irradiated mice, in part by investigating the hypothesis that two or more cell types are involved in recognition and rejection of hemopoietic cells. Interferon (IFN) was used as a tool for investigating such mechanisms. IFN alpha/beta stimulated the rejection of normal hemopoietic marrow cell grafts in Fl hybrid and in allogeneic host mice but did not affect the growth of cells in syngeneic mice. IFN alpha/beta was effective in hosts pretreated with silica but not in hosts pretreated with cyclophosphamide (Cy) or with anti-asialoGMI serum. Rabbit anti-IFN alpha/beta, but not anti-IFN gamma, serum inhibited genetic resistance to bone marrow cells. These results indicated that IFN alpha/beta was acting indirectly during the rejection of normal hemopoietic cells. It is proposed that four events occur in succession: a host cell recognizes the hemopoietic histocompatibility (Hh) antigens expressed on the surface of incompatible stem cells; this recognition leads to secretion of IFN; IFN activates natural killer (NK) cells; NK cells lyse donor stem cells. Silica interrupts one or both of the first two events. i.e., recognition and/or interrupts one or both of the first two events, i.e. recognition and/or IGN secretion.

  16. Bisphosphonates improve trabecular bone mass and normalize cortical thickness in ovariectomized, osteoblast connexin43 deficient mice.

    Science.gov (United States)

    Watkins, Marcus P; Norris, Jin Yi; Grimston, Susan K; Zhang, Xiaowen; Phipps, Roger J; Ebetino, Frank H; Civitelli, Roberto

    2012-10-01

    The gap junction protein, connexin43 (Cx43) controls both bone formation and osteoclastogenesis via osteoblasts and/or osteocytes. Cx43 has also been proposed to mediate an anti-apoptotic effect of bisphosphonates, potent inhibitors of bone resorption. We studied whether bisphosphonates are effective in protecting mice with a conditional Cx43 gene deletion in osteoblasts and osteocytes (cKO) from the consequences of ovariectomy on bone mass and strength. Ovariectomy resulted in rapid loss of trabecular bone followed by a slight recovery in wild type (WT) mice, and a similar degree of trabecular bone loss, albeit slightly delayed, occurred in cKO mice. Treatment with either risedronate (20 μg/kg) or alendronate (40 μg/kg) prevented ovariectomy-induced bone loss in both genotypes. In basal conditions, bones of cKO mice have larger marrow area, higher endocortical osteoclast number, and lower cortical thickness and strength relative to WT. Ovariectomy increased endocortical osteoclast number in WT but not in cKO mice. Both bisphosphonates prevented these increases in WT mice, and normalized endocortical osteoclast number, cortical thickness and bone strength in cKO mice. Thus, lack of osteoblast/osteocyte Cx43 does not alter bisphosphonate action on bone mass and strength in estrogen deficiency. These results support the notion that one of the main functions of Cx43 in cortical bone is to restrain osteoblast and/or osteocytes from inducing osteoclastogenesis at the endocortical surface. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Age sensitivity of behavioral tests and brain substrates of normal aging in mice.

    Science.gov (United States)

    Kennard, John A; Woodruff-Pak, Diana S

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  18. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    Directory of Open Access Journals (Sweden)

    John A. Kennard

    2011-05-01

    Full Text Available Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  19. Hybrid embryonic stem cell-derived tetraploid mice show apparently normal morphological, physiological, and neurological characteristics.

    Science.gov (United States)

    Schwenk, Frieder; Zevnik, Branko; Brüning, Jens; Röhl, Mathias; Willuweit, Antje; Rode, Anja; Hennek, Thomas; Kauselmann, Gunther; Jaenisch, Rudolf; Kühn, Ralf

    2003-06-01

    ES cell-tetraploid (ES) mice are completely derived from embryonic stem cells and can be obtained at high efficiency upon injection of hybrid ES cells into tetraploid blastocysts. This method allows the immediate generation of targeted mouse mutants from genetically modified ES cell clones, in contrast to the standard protocol, which involves the production of chimeras and several breeding steps. To provide a baseline for the analysis of ES mouse mutants, we performed a phenotypic characterization of wild-type B6129S6F(1) ES mice in relation to controls of the same age, sex, and genotype raised from normal matings. The comparison of 90 morphological, physiological, and behavioral parameters revealed elevated body weight and hematocrit as the only major difference of ES mice, which exhibited an otherwise normal phenotype. We further demonstrate that ES mouse mutants can be produced from mutant hybrid ES cells and analyzed within a period of only 4 months. Thus, ES mouse technology is a valid research tool for rapidly elucidating gene function in vivo.

  20. Nrf2 is required for normal postnatal bone acquisition in mice

    Institute of Scientific and Technical Information of China (English)

    Jung-Hyun Kim; Vandana Singhal; Shyam Biswal; Rajesh K Thimmulappa; Douglas J DiGirolamo

    2014-01-01

    A large body of literature suggests that bone metabolism is susceptible to the ill effects of reactive species that accumulate in the body and cause cellular dysfunction. One of the body’s front lines in defense against such damage is the transcription factor, Nrf2. This transcription factor regulates a plethora of antioxidant and cellular defense pathways to protect cells from such damage. Despite the breadth of knowledge of both the function of Nrf2 and the effects of reactive species in bone metabolism, the direct role of Nrf2 in skeletal biology has yet to be thoroughly examined. Thus, in the current study, we have examined the role of Nrf2 in postnatal bone metabolism in mice. Mice lacking Nrf2 (Nrf22/2) exhibited a marked deficit in postnatal bone acquisition, which was most severe at 3 weeks of age when osteoblast numbers were 12-fold less than observed in control animals. While primary osteoblasts from Nrf22/2 mice functioned normally in vitro, the colony forming capacity of bone marrow stromal cells (BMSCs) from these mice was significantly reduced compared to controls. This defect could be rescued through treatment with the radical scavenger N-acetyl cysteine (NAC), suggesting that increased reactive species stress might impair early osteoblastogenesis in BMSCs and lead to the failure of bone acquisition observed in Nrf22/2 animals. Taken together, these studies suggest Nrf2 represents a key pathway in regulating bone metabolism, which may provide future therapeutic targets to treat osteoporosis.

  1. Genital-tract infection and disease in nude and immunologically competent mice after inoculation of a human strain of Chlamydia trachomatis.

    OpenAIRE

    1982-01-01

    A fast, human strain of Chlamydia trachomatis was introduced into the uterus of progesterone-treated CBA mice and congenic CBA nude mice through the uterine wall or via the cervical canal. The numbers of inclusions produced by samples taken from the vagina of the nude mice were significantly greater (P less than 0.05) than those produced by samples from immunologically competent normal mice. However, the infection was self-limited, lasting about 60 days, and there was no statistical differenc...

  2. Calbindin distribution in cortical and subcortical brain structures of normal and rabies-infected mice.

    Science.gov (United States)

    Torres-Fernández, Orlando; Yepes, Gloria E; Gómez, Javier E; Pimienta, Hernán J

    2005-10-01

    Rabies has been an enigmatic disease of the nervous system because microscopic findings in the brain tissue are not paralleled by the severity of the clinical illness. The calcium binding protein calbindin (CB) is a neuronal marker of great interest in neuroanatomy and neuropathology. CB-ir neurons in the striatum and cerebral cortex are gabaergic cells. In the present work CB-immunoreactivity was evaluated in brains of normal and rabies-infected mice. Rabies infection caused loss of CB-immunostaining in the cortical supragranular layers as well as in the striatum. Loss of CB in the brains of mice infected with rabies virus can produce impairment in Ca++ homeostasis and in the gabaergic neurotransmission.

  3. Probiotics normalize the gut-brain-microbiota axis in immunodeficient mice.

    Science.gov (United States)

    Smith, Carli J; Emge, Jacob R; Berzins, Katrina; Lung, Lydia; Khamishon, Rebecca; Shah, Paarth; Rodrigues, David M; Sousa, Andrew J; Reardon, Colin; Sherman, Philip M; Barrett, Kim E; Gareau, Mélanie G

    2014-10-15

    The gut-brain-microbiota axis is increasingly recognized as an important regulator of intestinal physiology. Exposure to psychological stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis and causes altered intestinal barrier function, intestinal dysbiosis, and behavioral changes. The primary aim of this study was to determine whether the effects of psychological stress on intestinal physiology and behavior, including anxiety and memory, are mediated by the adaptive immune system. Furthermore, we wanted to determine whether treatment with probiotics would normalize these effects. Here we demonstrate that B and T cell-deficient Rag1(-/-) mice displayed altered baseline behaviors, including memory and anxiety, accompanied by an overactive HPA axis, increased intestinal secretory state, dysbiosis, and decreased hippocampal c-Fos expression. Both local (intestinal physiology and microbiota) and central (behavioral and hippocampal c-Fos) changes were normalized by pretreatment with probiotics, indicating an overall benefit on health conferred by changes in the microbiota, independent of lymphocytes. Taken together, these findings indicate a role for adaptive immune cells in maintaining normal intestinal and brain health in mice and show that probiotics can overcome this immune-mediated deficit in the gut-brain-microbiota axis. Copyright © 2014 the American Physiological Society.

  4. The Forkhead Transcription Factor, FOXP3, Is Required for Normal Pituitary Gonadotropin Expression in Mice1

    Science.gov (United States)

    Jung, Deborah O.; Jasurda, Jake S.; Egashira, Noboru; Ellsworth, Buffy S.

    2012-01-01

    ABSTRACT The hypothalamic-pituitary-gonadal axis is central to normal reproductive function. This pathway begins with the release of gonadotropin-releasing hormone in systematic pulses by the hypothalamus. Gonadotropin-releasing hormone is bound by receptors on gonadotroph cells in the anterior pituitary gland and stimulates the synthesis and secretion of luteinizing hormone and, to some extent, follicle-stimulating hormone. Once stimulated by these glycoprotein hormones, the gonads begin gametogenesis and the synthesis of sex hormones. In humans, mutations of the forkhead transcription factor, FOXP3, lead to an autoimmune disorder known as immunodysregulation, polyendocrinopathy, and enteropathy, X-linked syndrome. Mice with a mutation in the Foxp3 gene have a similar autoimmune syndrome and are infertile. To understand why FOXP3 is required for reproductive function, we are investigating the reproductive phenotype of Foxp3 mutant mice (Foxp3sf/Y). Although the gonadotroph cells appear to be intact in Foxp3sf/Y mice, luteinizing hormone beta (Lhb) and follicle-stimulating hormone beta (Fshb) expression are significantly decreased, demonstrating that these mice exhibit a hypogonadotropic hypogonadism. Hypothalamic expression of gonadotropin-releasing hormone is not significantly decreased in Foxp3sf/Y males. Treatment of Foxp3sf/Y males with a gonadotropin-releasing hormone receptor agonist does not rescue expression of Lhb or Fshb. Interestingly, we do not detect Foxp3 expression in the pituitary or hypothalamus, suggesting that the infertility seen in Foxp3sf/Y males is a secondary effect, possibly due to loss of FOXP3 in immune cells. Pituitary expression of glycoprotein hormone alpha (Cga) and prolactin (Prl) are significantly reduced in Foxp3sf/Y males, whereas the precursor for adrenocorticotropic hormone, pro-opiomelanocortin (Pomc), is increased. Human patients diagnosed with IPEX often exhibit thyroiditis due to destruction of the thyroid gland by

  5. Effects of propolis and gamma-cyclodextrin on intestinal neoplasia in normal weight and obese mice.

    Science.gov (United States)

    Cho, Youngjin; Gutierrez, Linda; Bordonaro, Michael; Russo, Daniel; Anzelmi, Frank; Hooven, Jayde T; Cerra, Carmine; Lazarova, Darina L

    2016-09-01

    Obesity is associated with colorectal cancer (CRC). This effect might be attributed to adipokine-supported signaling. We have established that propolis suppresses survival signaling in CRC cells in vitro; therefore, we ascertained the ability of a propolis supplement to modulate intestinal neoplastic development in C57BL/6J-ApcMin/+/J mice in the lean and obese state. To induce obesity, mice were fed with a Western diet containing 40% fat. Since the propolis supplement includes gamma-cyclodextrin, the interventions included diets supplemented with or without gamma-cyclodextrin. The animals were administered the following diets: (1) control diet, (2) control diet/gamma-cyclodextrin, (3) control diet/propolis, (4) Western diet, (5) Western diet/gamma-cyclodextrin, and (6) Western diet/propolis. Western diet, resulting in obesity, accelerated neoplastic progression, as evidenced by the larger size and higher grade dysplasia of the neoplasms. In the context of normal weight, gamma-cyclodextrin and propolis affected neoplastic progression, as determined by the size of the lesions and their grade of dysplasia. A statistically significant decrease in the number of adenomas was detected in mice fed a control diet with the propolis supplement (61.8 ± 10.6 vs. 35.3 ± 7.6, P = 0.008). Although there was no significant difference in the polyp numbers between the six groups, the mice with the lowest number and size of adenomas were those fed a Western diet with gamma-cyclodextrin. This unexpected outcome might be explained by the increased levels of apoptosis detected in the intestinal tissues of these obese mice. We posit that butyrate derived from the metabolism of gamma-cyclodextrin may contribute to the decreased neoplastic burden in the context of obesity; however, future studies are required to address this possibility.

  6. Pathogenicity of Candida viswanathii for normal and cortisone-treated mice.

    Science.gov (United States)

    Randhawa, H S; Mishra, S K; Damodaran, V N; Prakash, A; Chowdhary, A; Khan, Z U

    2015-12-01

    The pathogenicity of Candida viswanathii, PCI 501/1 (CBS 4024), originally isolated from CSF of a fatal case of meningitis in India, is reported. Also, included is a global overview of the occurrence of C. viswanathii in clinical and environmental sources. The investigation was done in normal and cortisone-treated albino mice challenged intravenously with variable doses of 1×10(6), 4×10(6) and 16×10(6) actively growing yeast cells of the fungus. The animals were kept under observation up to 3 weeks when they were sacrificed for a mycological and histopathologic study. As apparent from the data on morbidity and mortality, the species exhibited low virulence for normal mice, whereas it caused significantly higher mortality (Pcortisone group. Likewise, there was overall higher recovery of C. viswanathii in culture from the cortisone-treated than in the normal group of mice. These observations are indicative of C. viswanathii being an opportunistic pathogen. It is recognized that a definitive identification of C. viswanathii requires mycological expertise for comprehensive phenotypic characterization or the application of expensive techniques such as Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) and molecular techniques, facilities for which are generally lacking in a vast majority of laboratory diagnostic centers especially in developing countries. Consequently, the prevalence of C. viswanathii in clinical and environmental samples is currently likely to be underestimated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. Synthesis and biodistribution of 2-[{sup 123}I]iodomelatonin in normal mice

    Energy Technology Data Exchange (ETDEWEB)

    Al-Jammaz, I. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)]. E-mail: jammaz@kfshrc.edu.sa; Al-Otaibi, B. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Aboul-Enein, H. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia); Amartey, J.K. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211 (Saudi Arabia)

    2006-01-01

    Melatonin demands that this hormone and its receptors be well understood. With this aim in mind, synthetic melatonin was radioiodinated with no-carrier-added (n.c.a.) sodium iodide-123 using in situ generated peracetic acid as oxidizing agent for electrophilic iodination at room temperature. The radiochemical yield was typically greater than 80% after 20 min reaction time especially when relatively small amounts of activities were used (10 mCi). Biological evaluation was performed in normal mice. The distribution of the tracer did not reveal any specificity during the time frame studied. There was no significant retention in the whole brain.

  8. Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice

    Science.gov (United States)

    Takayanagi, Yuki; Yoshida, Masahide; Bielsky, Isadora F.; Ross, Heather E.; Kawamata, Masaki; Onaka, Tatsushi; Yanagisawa, Teruyuki; Kimura, Tadashi; Matzuk, Martin M.; Young, Larry J.; Nishimori, Katsuhiko

    2005-01-01

    The oxytocin receptor (OXTR) and its ligand, oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene (Oxtr-/-) and compared them with OXT-deficient (Oxt-/-) mice. Oxtr-/- mice were viable and had no obvious deficits in fertility or reproductive behavior. Oxtr-/- dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing. Infant Oxtr-/- males emitted fewer ultrasonic vocalizations than wild-type littermates in response to social isolation. Adult Oxtr-/- males also showed deficits in social discrimination and elevated aggressive behavior. Ligand Oxt-/- males from Oxt-/- dams, but not from Oxt+/- dams, showed similar high levels of aggression. These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior. Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior. PMID:16249339

  9. Requirement of the RNA-editing enzyme ADAR2 for normal physiology in mice.

    Science.gov (United States)

    Horsch, Marion; Seeburg, Peter H; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Garrett, Lilian; Götz, Alexander; Hans, Wolfgang; Higuchi, Miyoko; Hölter, Sabine M; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Adamski, Jerzy; Busch, Dirk H; Esposito, Irene; Graw, Jochen; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Mempel, Martin; Ollert, Markus; Schulz, Holger; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Gailus-Durner, Valérie; Fuchs, Helmut; de Angelis, Martin Hrabe; Beckers, Johannes

    2011-05-27

    ADAR2, an RNA editing enzyme that converts specific adenosines to inosines in certain pre-mRNAs, often leading to amino acid substitutions in the encoded proteins, is mainly expressed in brain. Of all ADAR2-mediated edits, a single one in the pre-mRNA of the AMPA receptor subunit GluA2 is essential for survival. Hence, early postnatal death of mice lacking ADAR2 is averted when the critical edit is engineered into both GluA2 encoding Gria2 alleles. Adar2(-/-)/Gria2(R/R) mice display normal appearance and life span, but the general phenotypic effects of global lack of ADAR2 have remained unexplored. Here we have employed the Adar2(-/-)/Gria2(R/R) mouse line, and Gria2(R/R) mice as controls, to study the phenotypic consequences of loss of all ADAR2-mediated edits except the critical one in GluA2. Our extended phenotypic analysis covering ∼320 parameters identified significant changes related to absence of ADAR2 in behavior, hearing ability, allergy parameters and transcript profiles of brain.

  10. Requirement of the RNA-editing Enzyme ADAR2 for Normal Physiology in Mice*

    Science.gov (United States)

    Horsch, Marion; Seeburg, Peter H.; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Becker, Lore; Calzada-Wack, Julia; Garrett, Lilian; Götz, Alexander; Hans, Wolfgang; Higuchi, Miyoko; Hölter, Sabine M.; Naton, Beatrix; Prehn, Cornelia; Puk, Oliver; Rácz, Ildikó; Rathkolb, Birgit; Rozman, Jan; Schrewe, Anja; Adamski, Jerzy; Busch, Dirk H.; Esposito, Irene; Graw, Jochen; Ivandic, Boris; Klingenspor, Martin; Klopstock, Thomas; Mempel, Martin; Ollert, Markus; Schulz, Holger; Wolf, Eckhard; Wurst, Wolfgang; Zimmer, Andreas; Gailus-Durner, Valérie; Fuchs, Helmut; de Angelis, Martin Hrabě; Beckers, Johannes

    2011-01-01

    ADAR2, an RNA editing enzyme that converts specific adenosines to inosines in certain pre-mRNAs, often leading to amino acid substitutions in the encoded proteins, is mainly expressed in brain. Of all ADAR2-mediated edits, a single one in the pre-mRNA of the AMPA receptor subunit GluA2 is essential for survival. Hence, early postnatal death of mice lacking ADAR2 is averted when the critical edit is engineered into both GluA2 encoding Gria2 alleles. Adar2−/−/Gria2R/R mice display normal appearance and life span, but the general phenotypic effects of global lack of ADAR2 have remained unexplored. Here we have employed the Adar2−/−/Gria2R/R mouse line, and Gria2R/R mice as controls, to study the phenotypic consequences of loss of all ADAR2-mediated edits except the critical one in GluA2. Our extended phenotypic analysis covering ∼320 parameters identified significant changes related to absence of ADAR2 in behavior, hearing ability, allergy parameters and transcript profiles of brain. PMID:21467037

  11. Glycaemic effects of traditional European plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice.

    Science.gov (United States)

    Swanston-Flatt, S K; Day, C; Flatt, P R; Gould, B J; Bailey, C J

    1989-02-01

    Twelve plants used for the traditional treatment of diabetes mellitus in northern Europe were studied using normal and streptozotocin diabetic mice to evaluate effects on glucose homeostasis. The plants were administered in the diet (6.25% by weight) and/or as decoctions or infusions in place of drinking water, to coincide with the traditional method of preparation. Treatment for 28 days with preparations of burdock (Arctium lappa), cashew (Anacardium occidentale), dandelion (Taraxacum officinale), elder (Sambucus nigra), fenugreek (Trigonella foenum-graecum), guayusa (Ilex guayusa), hop (Humulus lupulus), nettle (Urtica dioica), cultivated mushroom (Agaricus bisporus), periwinkle (Catharanthus roseus), sage (Salvia officinale), and wild carrot (Daucus carrota) did not affect the parameters of glucose homeostasis examined in normal mice (basal plasma glucose and insulin, glucose tolerance, insulin-induced hypoglycaemia and glycated haemoglobin). After administration of streptozotocin (200 mg/kg) burdock and nettle aggravated the diabetic condition, while cashew, dandelion, elder, fenugreek, hop, periwinkle, sage and wild carrot did not significantly affect the parameters of glucose homeostasis studied (basal glucose and insulin, insulin-induced hypoglycaemia, glycated haemoglobin and pancreatic insulin concentration). Guayusa and mushroom retarded the development of hyperglycaemia in streptozotocin diabetes and reduced the hyperphagia, polydipsia, body weight loss, and glycated haemoglobin. Mushroom also countered the initial reduction in plasma insulin and the reduction in pancreatic insulin concentration, and improved the hypoglycaemic effect of exogenous insulin. These studies suggest the presence of potentially useful antidiabetic agents in guayusa and mushroom.

  12. Dynamics of oligodendrocyte responses to anterograde axonal (Wallerian) and terminal degeneration in normal and TNF-transgenic mice

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Fenger, Christina; Nielsen, Helle H

    2004-01-01

    degeneration and lesion-induced axonal sprouting in the hippocampal dentate gyrus in TNF-transgenic mice with the response in genetically normal mice. Transectioning of the entorhino-dentate perforant path axonal projection increased hippocampal TNF mRNA expression in both types of mice, but to significantly...... larger levels in the TNF-transgenics. At 5 days after axonal transection, numbers of oligodendrocytes and myelin basic protein (MBP) mRNA expression in the denervated dentate gyrus in TNF-transgenic mice had increased to the same extent as in nontransgenic littermates. At this time, transgenics showed...

  13. Brown Norway chromosome 1 congenic reduces symptoms of renal disease in fatty Zucker rats.

    Science.gov (United States)

    Warden, Craig H; Slupsky, Carolyn; Griffey, Stephen M; Bettaieb, Ahmed; Min, Esther; Le, Anh; Fisler, Janis S; Hansen, Susan; Haj, Fawaz; Stern, Judith S

    2014-01-01

    We previously reported that a congenic rat with Brown Norway (BN) alleles on chromosome 1 reduces renal disease of 15-week old fatty Zucker rats (ZUC). Development of renal disease in fatty BN congenic and fatty ZUC rats from 9 through 28 weeks is now examined. Analysis of urine metabolites by (1)H nuclear magnetic resonance (NMR) spectroscopy revealed a significantly increased urinary loss of glucose, myo-inositol, urea, creatine, and valine in ZUC. Food intake was lower in the BN congenic rats at weeks 9-24, but they weighed significantly more at 28 weeks compared with the ZUC group. Fasting glucose was significantly higher in ZUC than congenic and adiponectin levels were significantly lower in ZUC, but there was no significant genotype effect on Insulin levels. Glucose tolerance tests exhibited no significant differences between ZUC and congenic when values were normalized to basal glucose levels. Quantitative PCR on livers revealed evidence for higher gluconeogenesis in congenics than ZUC at 9 weeks. Plasma urea nitrogen and creatinine were more than 2-fold higher in 28-week ZUC. Twelve urine protein markers of glomerular, proximal and distal tubule disease were assayed at three ages. Several proteins that indicate glomerular and proximal tubular disease increased with age in both congenic and ZUC. Epidermal growth factor (EGF) level, a marker whose levels decrease with distal tubule disease, was significantly higher in congenics. Quantitative histology of 28 week old animals revealed the most significant genotype effect was for tubular dilation and intratubular protein. The congenic donor region is protective of kidney disease, and effects on Type 2 diabetes are likely limited to fasting glucose and adiponectin. The loss of urea together with a small increase of food intake in ZUC support the hypothesis that nitrogen balance is altered in ZUC from an early age.

  14. Normal phenotype in conditional androgen receptor (AR) exon 3-floxed neomycin-negative male mice.

    Science.gov (United States)

    Rana, Kesha; Clarke, Michele V; Zajac, Jeffrey D; Davey, Rachel A; MacLean, Helen E

    2014-01-01

    Androgens (testosterone and dihydrotestosterone) acting via the androgen receptor (AR) are required for male sexual differentiation, and also regulate the development of many other tissues including muscle, fat and bone. We previously generated an AR(lox) mouse line with exon 3 of the AR gene targeted by loxP sites. The deletion of exon 3 is in-frame, so only the DNA binding-dependent actions of the AR are deleted, but non-DNA binding-dependent actions are retained. This line also contained an antibiotic resistance selection cassette, neomycin (neo) in intron 3, which was also flanked by loxP sites. Hemizygous AR(lox) male mice demonstrated a phenotype of hyperandrogenization, with increased mass of androgen-dependent tissues. We hypothesized that this hyperandrogenization was likely to be due to the presence of the neo cassette. In this study, we have generated an AR(lox) neo-negative mouse line, using the EIIa-cre deleter mouse line to remove the neo cassette. Hemizygous AR(lox) neo-negative male mice have a normal phenotype, with normal body mass and normal mass of androgen-dependent tissues including the testis, seminal vesicles, kidney, spleen, heart and retroperitoneal fat. This neo-negative exon 3-targeted mouse line is the only floxed AR mouse line available to study the DNA binding-dependent actions of the AR in a tissue-specific manner, and is suitable for investigation in all tissues. This study demonstrates the importance of removing the selection cassette, which can potentially alter the phenotype of floxed mouse lines even in the absence of detectable effects on target gene expression.

  15. Effects of a high-monounsaturated fat diet on glucose and lipid metabolisms in normal and diabetic mice.

    Science.gov (United States)

    Kotake, Jiro; Tanaka, Yoshiaki; Umehara, Norimitsu; Miyashita, Akira; Tsuru, Tomomitsu; Hikida, Shigeki; Mizote, Hiroyoshi

    2004-04-01

    The beneficial effects of high-monounsaturated fat (high-MUFA) diets on diabetic patients have been reported, whereas studies concerning the effects on animals have been few. Although experiments on animals should be useful in elucidating underlying mechanisms, it is not clear even whether there are benefits of a high-MUFA diet in animals. This study examined the short-term effects of a high-MUFA diet on normal and genetically diabetic mice. The high-MUFA diet supplied 38% of the total calories as fat (26% from MUFA), while a regular diet was 13% fat (3% from MUFA). Normal C5 7BL/6J and diabetic C57BL/KsJ-db/db mice were fed either the regular or the high-MUFA diet for 1 wk. Serum glucose and lipid levels were then measured. In normal mice, hepatic triglyceride production was also compared between the two dietary groups using the Triton WR1339 method. An oral glucose tolerance test was conducted on the diabetic mice. After 1 wk of feeding to normal mice, the high-MUFA diet was seen to lower serum triglyceride levels and reduce hepatic triglyceride production in comparison with the regular diet; it is suggested that the lowering of triglyceride consists of mechanisms including reduced hepatic triglyceride production. When diabetic mice were fed the high-MUFA diet with a controlled caloric intake, the serum glucose levels lowered without an accompanying deterioration in lipid metabolism and the impaired glucose tolerance was ameliorated. This study demonstrates that a high-MUFA diet can lower serum triglyceride levels in normal mice and improve disorders of glucose metabolism in diabetic mice.

  16. Metabolic effects of a stabilizing peptide fusion protein of leptin in normal mice.

    Science.gov (United States)

    Park, H; Lee, S-B; Koh, J; Kim, J

    2012-06-01

    Leptin is a protein hormone produced by adipocytes. It is secreted into the blood stream and plays a key role in regulating body energy homeostasis by inhibiting feeding behavior followed by decreased body weight. Because protein aggregation is a major problem in therapeutic proteins, we previously demonstrated that a stabilizing peptide (SP) fusion protein of leptin (SP-leptin) appeared to resist aggregation induced by agitation, freezing/thawing, or heat stress. In this study, we fused mouse leptin with the stabilizing peptide and compared the biological activities of leptin and SP-leptin in vivo using a male C57Bl mouse model and ex vivo using MCF7 breast cancer cell lines. Each group of mice was treated with saline, leptin, and SP-leptin for 20 days and the differences in body weight, food intake, abdominal fat contents, and TG concentration were measured. The SP-leptin appeared to decrease the body weight and food intake in male C57Bl mice more significantly than wild type leptin, and the SP-leptin treated MCF7 cells displayed better cell proliferation than leptin. As a consequence of decreased body weight, the SP-leptin treated mouse group showed decreased abdominal fat contents and low triglyceride (TG) concentration. Moreover, the SP-leptin treated mouse group had fewer lipid droplets in liver and reduced lipid droplet size when analyzed by Oil red O and H & E staining. These results demonstrated that SP-leptin is more effective than wild type leptin in normal mice in lowering their body weight and fat contents in the abdominal region, the serum, and the liver.

  17. Genome-wide expression analysis comparing hypertrophic changes in normal and dysferlinopathy mice

    Directory of Open Access Journals (Sweden)

    Yun-Sil Lee

    2015-12-01

    Full Text Available Because myostatin normally limits skeletal muscle growth, there are extensive efforts to develop myostatin inhibitors for clinical use. One potential concern is that in muscle degenerative diseases, inducing hypertrophy may increase stress on dystrophic fibers. Our study shows that blocking this pathway in dysferlin deficient mice results in early improvement in histopathology but ultimately accelerates muscle degeneration. Hence, benefits of this approach should be weighed against these potential detrimental effects. Here, we present detailed experimental methods and analysis for the gene expression profiling described in our recently published study in Human Molecular Genetics (Lee et al., 2015. Our data sets have been deposited in the Gene Expression Omnibus (GEO database (GSE62945 and are available at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62945. Our data provide a resource for exploring molecular mechanisms that are related to hypertrophy-induced, accelerated muscular degeneration in dysferlinopathy.

  18. Markers of Alzheimer’s Disease in Primary Visual Cortex in Normal Aging in Mice

    Directory of Open Access Journals (Sweden)

    Luis Fernando Hernández-Zimbrón

    2017-01-01

    Full Text Available Aging is the principal risk factor for the development of Alzheimer’s disease (AD. The hallmarks of AD are accumulation of the amyloid-β peptide 1–42 (Aβ42 and abnormal hyperphosphorylation of Tau (p-Tau protein in different areas of the brain and, more recently reported, in the visual cortex. Recently, Aβ42 peptide overproduction has been involved in visual loss. Similar to AD, in normal aging, there is a significant amyloid deposition related to the overactivation of the aforementioned mechanisms. However, the mechanisms associated with visual loss secondary to age-induced visual cortex affectation are not completely understood. Young and aged mice were used as model to analyze the presence of Aβ42, p-Tau, glial-acidic fibrillary protein (GFAP, and presenilin-2, one of the main enzymes involved in Aβ42 production. Our results show a significant increase of Aβ42 deposition in aged mice in the following cells and/or tissues: endothelial cells and blood vessels and neurons of the visual cortex; they also show an increase of the expression of GFAP and presenilin-2 in this region. These results provide a comprehensive framework for the role of Aβ42 in visual loss due to inflammation present with aging and offer some clues for fruitful avenues for the study of healthy aging.

  19. Lipodystrophy, Diabetes and Normal Serum Insulin in PPARγ-Deficient Neonatal Mice

    Science.gov (United States)

    O’Donnell, Peter E.; Ye, Xiu Zhen; DeChellis, Melissa A.; Davis, Vannessa M.; Duan, Sheng Zhong; Mortensen, Richard M.; Milstone, David S.

    2016-01-01

    Peroxisome proliferator activated receptor gamma (PPARγ) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPARγ also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPARγ in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPARγ. PPARγ-rescued placentas support development of PPARγ-deficient embryos that are viable and born in near normal numbers. However, PPARγ-deficient neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal hepatitis, relative insulin deficiency and diabetes beginning soon after birth and culminating in failure to thrive and neonatal lethality between 4 and 10 days of age. These abnormalities are not observed with selective PPARγ2 deficiency or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes, cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest important but previously unappreciated functions for PPARγ1 in the neonatal period either alone or in combination with PPARγ2 in lipid metabolism, glucose homeostasis and insulin sensitivity. PMID:27505464

  20. Sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice.

    Directory of Open Access Journals (Sweden)

    Carl Johan Drott

    Full Text Available Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1, that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10-12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10-12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10-12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only ∼15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life.

  1. 129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal.

    Science.gov (United States)

    Manson, J C; Clarke, A R; Hooper, M L; Aitchison, L; McConnell, I; Hope, J

    1994-01-01

    The neural membrane glycoprotein PrP is implicated in the pathogenesis of the transmissible spongiform encephalopathies; however, the normal function of PrP and its precise role in disease are not understood. Recently, gene targeting has been used to produce mice with neo/PrP fusion transcripts, but no detectable PrP protein in the brain (1). Here we report the use of a different targeting strategy, to produce inbred mice with a complete absence of both PrP protein and mRNA sequences. At 7 mo of age, these mice show no overt phenotypic abnormalities despite the normal high levels of expression of PrP during mouse development. The mice are being used in experiments designed to address the role of PrP in the pathogenesis of scrapie and the replication of infectivity.

  2. Hymenolepis nana: worm recovery from congenitally athymic nude and phenotypically normal rats and mice.

    Science.gov (United States)

    Ito, A; Kamiyama, T

    1984-10-01

    When eggs or mouse-derived cysticercoids of Hymenolepis nana were inoculated into previously uninfected congenitally athymic nude (rnu/rnu) rats of an outbred Rowett strain, they failed to mature in the intestinal lumen. They also failed to mature in phenotypically normal (rnu/+) littermates, except when these hosts were treated with cortisone acetate from the beginning of the lumen phase. The Rowett rat, either thymus-deficient or not, was susceptible to tissue cysticercoids but resistant to luminal adults. It is therefore considered to be an unnatural host, at least for mouse-derived H. nana. There was little or no difference in susceptibility to initial tissue cysticercoids between these nude rats and phenotypically normal ones. The normal rats became completely resistant to reinfection with eggs and no secondary cysticercoids developed in their intestinal tissue, whereas the nude rats showed unaltered susceptibility to secondary tissue cysticercoids. Thus, acquired resistance to egg challenge, assessed by the failure of tissue cysticercoid recovery, was thymus-dependent. However, innate resistance to both a primary egg dose, assessed by the low recovery rates of tissue cysticercoids, and to a primary cysticercoid dose, assessed by the failure of luminal adult recovery, were thymus-independent. The effect of cortisone acetate to initiate maturation of H. nana appeared to be unrelated to thymus function. In contrast, all mice, either thymus-deficient or not, were highly susceptible to both phases. The number of worms recovered was more than 10 times greater than that of cysticercoids established in the rat's intestinal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Narp knockout mice show normal reactivity to novelty but attenuated recovery from neophobia.

    Science.gov (United States)

    Blouin, Ashley M; Lee, Jongah J; Tao, Bo; Smith, Dani R; Johnson, Alexander W; Baraban, Jay M; Reti, Irving M

    2013-11-15

    Narp knockout (KO) mice demonstrate cognitive inflexibility and addictive behavior, which are associated with abnormal reactivity to a novel stimulus. To assess reactivity to novelty, we tested Narp KO and wild-type (WT) mice on a neophobia procedure. Both Narp KO and WT mice showed a similar decrease in consumption upon initial exposure to a novel flavor, but Narp KO mice did not increase consumption with subsequent exposures to the novel flavor like the WT mice. Therefore, Narp KO mice do not have abnormal reactivity to novelty but show deficits in adapting behavior to reflect the updated value of a stimulus.

  4. Fog2 is required for normal diaphragm and lung development in mice and humans.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Congenital diaphragmatic hernia and other congenital diaphragmatic defects are associated with significant mortality and morbidity in neonates; however, the molecular basis of these developmental anomalies is unknown. In an analysis of E18.5 embryos derived from mice treated with N-ethyl-N-nitrosourea, we identified a mutation that causes pulmonary hypoplasia and abnormal diaphragmatic development. Fog2 (Zfpm2 maps within the recombinant interval carrying the N-ethyl-N-nitrosourea-induced mutation, and DNA sequencing of Fog2 identified a mutation in a splice donor site that generates an abnormal transcript encoding a truncated protein. Human autopsy cases with diaphragmatic defect and pulmonary hypoplasia were evaluated for mutations in FOG2. Sequence analysis revealed a de novo mutation resulting in a premature stop codon in a child who died on the first day of life secondary to severe bilateral pulmonary hypoplasia and an abnormally muscularized diaphragm. Using a phenotype-driven approach, we have established that Fog2 is required for normal diaphragm and lung development, a role that has not been previously appreciated. FOG2 is the first gene implicated in the pathogenesis of nonsyndromic human congenital diaphragmatic defects, and its necessity for pulmonary development validates the hypothesis that neonates with congenital diaphragmatic hernia may also have primary pulmonary developmental abnormalities.

  5. Erythrocytes encapsulated with phenylalanine hydroxylase exhibit improved pharmacokinetics and lowered plasma phenylalanine levels in normal mice.

    Science.gov (United States)

    Yew, Nelson S; Dufour, Emmanuelle; Przybylska, Malgorzata; Putelat, Julie; Crawley, Cristin; Foster, Meta; Gentry, Sarah; Reczek, David; Kloss, Alla; Meyzaud, Aurélien; Horand, Françoise; Cheng, Seng H; Godfrin, Yann

    2013-08-01

    Enzyme replacement therapy is often hampered by the rapid clearance and degradation of the administered enzyme, limiting its efficacy and requiring frequent dosing. Encapsulation of therapeutic molecules into red blood cells (RBCs) is a clinically proven approach to improve the pharmacokinetics and efficacy of biologics and small molecule drugs. Here we evaluated the ability of RBCs encapsulated with phenylalanine hydroxylase (PAH) to metabolize phenylalanine (Phe) from the blood and confer sustained enzymatic activity in the circulation. Significant quantities of PAH were successfully encapsulated within murine RBCs (PAH-RBCs) with minimal loss of endogenous hemoglobin. While intravenously administered free PAH enzyme was rapidly eliminated from the blood within a few hours, PAH-RBCs persisted in the circulation for at least 10days. A single injection of PAH-RBCs was able to decrease Phe levels by nearly 80% in normal mice. These results demonstrate the ability of enzyme-loaded RBCs to metabolize circulating amino acids and highlight the potential to treat disorders of amino acid metabolism.

  6. Fgf8-deficient mice compensate for reduced GnRH neuronal population and exhibit normal testicular function

    Directory of Open Access Journals (Sweden)

    Wei eZhang

    2015-09-01

    Full Text Available Gonadotropin-releasing hormone (GnRH is critical for the onset and maintenance of reproduction in vertebrates. The development of GnRH neurons is highly dependent on fibroblast growth factor (Fgf signaling. Mice with a hypomorphic Fgf8 allele (Fgf8 Het exhibited a ~50% reduction in GnRH neuron number at birth. Female Fgf8 Het mice were fertile but showed significantly delayed puberty. However, it was unclear if these mice suffered additional loss of GnRH neurons after birth, and if male Fgf8 Het mice had normal pubertal transition and testicular function. In this study, we examined postnatal GnRH neuron number and hypothalamic GnRH content in Fgf8 Het mice from birth to 120 days of age. Further, we examined seminal vesicle and testicular growth, testicular histology, and circulating luteinizing hormone (LH around and after pubertal transition. Our results showed that GnRH neuron numbers were significantly and consistently reduced in Fgf8 Het mice of both sexes in all ages examined, suggesting these animals were born with an inherently defective GnRH system, and no further postnatal loss of GnRH neurons had occurred. Despite an innately compromised GnRH system, male and female Fgf8 mice exhibited normal levels of immunoassayable hypothalamic GnRH peptide at all ages examined except on 60 days of age, suggesting increased GnRH synthesis or reduced turnover as a compensatory mechanism. Fgf8 Het males also had normal seminal vesicle and testicular mass/body mass ratios, testicular histology, and circulating LH. Overall, our data speak to the extraordinary ability of a GnRH system permanently compromised by developmental defect to overcome pre-existing deficiencies to ensure pubertal progression and reproduction.

  7. Virus expression in different tissues of normal and tumor-bearing mice inoculated with a murine leukemia virus.

    Science.gov (United States)

    Youn, J K; Santillana, M; Hue, G; Barski, G

    1977-11-15

    Evolution of virus expression in different lymphoid organs as well as in solid syngeneic tumors of mice inoculated with an MuLV was studied with the aid of in vitro XC co-culture technique. When normal adult mice of strain XLII were inoculated intraperitoneally with a cultured Rauscher virus (RC), the virus could be detected, 10 days after inoculation, only in bone marrow in small amounts and thereafter no virus could be found in any of the organs tested, including bone marrow, spleen, thymus, lymph node and kidney. However, when age- and sex-matched parallel mice bearing syngeneic subcutaneous non-viral tumors were inoculated similarly with the RC virus, the virus could be detected abundantly not only in bone marrow and spleen but also in tumors during the first 3 weeks and even 6 weeks after virus inoculation. Transitional decrease or disappearance of the virus was observed around the 25th-31st day in organs and tumors of the inoculated mice. When the tumor mass was removed from these mice by surgery, the virus disappeared rapidly and definitely from all the organs tested. The virus recovered from in vitro explanted and cultured tumors, taken from mice inoculated with the virus, induced typical lymphoid leukemia in BALB/c mice inoculated as newborns. However, from certain aspects (hypertrophy of the thymus and lymph nodes), this virus was different from the original RC virus.

  8. Congener Production in Blood Samples During Preparation and Storage

    DEFF Research Database (Denmark)

    Felby, Søren; Nielsen, Erik

    1995-01-01

    Retsmedicin, congener production, preparation, head space GC, acetone, isobutanol, storage, blood samples, n-propanol, methanol, methylethylketone......Retsmedicin, congener production, preparation, head space GC, acetone, isobutanol, storage, blood samples, n-propanol, methanol, methylethylketone...

  9. Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer

    Institute of Scientific and Technical Information of China (English)

    Lei LI; Fang LE; Li-ya WANG; Xiang-rong XU; Hang-ying LOU; Ying-ming ZHENG; Jiang-zhong SHENG; He-feng HUANG; Fan JIN

    2011-01-01

    An association between assisted reproductive technology (ART) and neurobehavioral imprinting disorders has been reported in many studies,and it seems that ART may interfere with imprint reprogramming.However,it has never been explored whether epigenetic errors or imprinting disease susceptibility induced by ART can be inherited transgenerationally.Hence,the aim of this study was to determine the effect of in vitro fertilization and embryo transfer (IVF-ET) on transgenerational inheritance in an inbred mouse model.Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations.Their behavior,morphology,histology,and DNA methylation status at several important differentially methylated regions (DMRs) were analyzed by Morris water maze,hematoxylin and eosin (H&E) staining,and bisulfite genomic sequencing.No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF (F1) and female and male line F2 and F3 generations.A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation (0.40±0.118,P=0.086).Methylation status in H19/Igf2 DMR island 1,Igf2 DMR,KvDMR,and Snrpn DMR displayed normal patterns.Methylation percentage did not differ significantly from that of adults conceived naturally,and the expression of the genes they regulated was not disturbed.Transgenerational integrity,such as behavior,morphology,histology,and DNA methylation status,was maintained in these generations,which indicates that exposure of female germ cells to hormonal stimulation and gamete manipulation might not affect the individuals and their descendents.

  10. Normalizing the environment recapitulates adult human immune traits in laboratory mice.

    Science.gov (United States)

    Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

    2016-04-28

    Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

  11. The acyl-CoA binding protein is required for normal epidermal barrier function in mice

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Bek, Signe; Marcher, Ann-Britt;

    2012-01-01

    The acyl-CoA binding protein (ACBP) is a 10 kDa intracellular protein expressed in all eukaryotic species. Mice with targeted disruption of Acbp (ACBP(-/-) mice) are viable and fertile but present a visible skin and fur phenotype characterized by greasy fur and development of alopecia and scaling...

  12. Expression of human hormone-sensitive lipase (HSL) in postmeiotic germ cells confers normal fertility to HSL-deficient mice.

    Science.gov (United States)

    Wang, Shu Pei; Chung, Shari; Soni, Krishnakant; Bourdages, Hugo; Hermo, Louis; Trasler, Jacquetta; Mitchell, Grant A

    2004-12-01

    Hormone-sensitive lipase (HSL, Lipe, E.C.3.1.1.3) is a multifunctional fatty acyl esterase that is essential for male fertility and spermatogenesis and that also plays important roles in the function of adipocytes, pancreatic beta-cells, and adrenal cortical cells. Gene-targeted HSL-deficient (HSL-/-) male mice are infertile, have a 2-fold reduction in testicular mass, a 2-fold elevation of the ratio of esterified to free cholesterol in testis, and unique morphological abnormalities in round and elongating spermatids. Postmeiotic germ cells in the testis express a specific HSL isoform. We created transgenic mice expressing a normal human testicular HSL cDNA from the mouse protamine-1 promoter, which mediates expression specifically in postmeiotic germ cells. Testicular cholesteryl esterase activity was undetectable in HSL-/- mice, but in HSL-/- males expressing the testicular transgene, activity was 2-fold greater than normal. HSL transgene mRNA became detectable in testes between 19 and 25 days of age, coinciding with the first wave of postmeiotic transcription in round spermatids. In contrast to nontransgenic HSL-/- mice, HSL-/- males expressing the testicular transgene were normal with respect to fertility, testicular mass, testicular esterified/free cholesterol ratio, and testicular histology. Their cauda epididymides contained abundant, normal-appearing spermatozoa. We conclude that human testicular HSL is functional in mouse testis and that the mechanism of infertility in HSL-deficient males is cell autonomous and resides in postmeiotic germ cells, because HSL expression in these cells is in itself sufficient to restore normal fertility.

  13. Correlation between human maternal-fetal placental transfer and molecular weight of PCB and dioxin congeners/isomers.

    Science.gov (United States)

    Mori, Chisato; Nakamura, Noriko; Todaka, Emiko; Fujisaki, Takeyoshi; Matsuno, Yoshiharu; Nakaoka, Hiroko; Hanazato, Masamichi

    2014-11-01

    Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Comparative metabolism of Radix scutellariae extract by intestinal bacteria from normal and type 2 diabetic mice in vitro.

    Science.gov (United States)

    Xu, Jun; Zhao, Min; Qian, Dawei; Shang, Er-xin; Jiang, Shu; Guo, Jianming; Duan, Jin-ao; Du, Leyue

    2014-04-28

    Traditional Chinese medicine (TCM) has been used in clinical practice for several thousand years. TCM has played an indispensable role in the prevention and treatment of disease, especially the complicated and chronic ones. In TCMs, many ingredients which are known to have biological effects just pass through the gut, they do not get into the bloodstream. Study on interactions of these active ingredients with the intestinal bacteria is very helpful to unravel how TCM works. Radix scutellariae was widely used alone or in combination with other medicinal herbs to the treatment of type 2 diabetes mellitus for a long time in China even in Asia. Additionally, the incidence of type 2 diabetes is closely related to the changes of intestinal flora. In this paper, the metabolism of baicalin in Radix scutellariae extract by normal and type 2 diabetic mice intestinal bacteria were firstly investigated. Ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/QTOF-MS) technique combined with Metabolynx(TM) software was used for analysis of the metabolic profile of baicalin in Radix scutellariae extracts by the intestinal bacteria from normal and type 2 diabetic mice. The amount of baicalin׳s aglycone (baicalein) in type 2 diabetic mice samples were remarkably more than that in normal mice samples and oroxylin A only existed in type 2 diabetic mice samples. Intestinal bacteria produced not only a small amount of baicalein, but also some conjugates such as hydrogenated baicalin and methylated baicalin. We proposed that β-d-glucuronidases contributed to the deglycosylation prior to absorption. Intestinal bacteria from pathological state mice produced more baicalein, which was well absorbed contributing to the treatment of type 2 diabetes. Additionally, the pharmacological effects of oroxylin A were associated with type 2 diabetes. Hence, the production of metabolites of baicalin might influence the effects of traditional medicines. Thus the

  15. Ultrastructure and morphometry of the urethral glands in normal, castrated, and testosterone-treated castrated male mice.

    Science.gov (United States)

    Parr, M B; Ren, H P; Kepple, L; Parr, E L; Russell, L D

    1993-07-01

    Recent studies of the urethral glands in the male mouse and rat have suggested that they are testosterone-dependent glands that may be potential sites for secretory immunity in the male genital tract. In the present study we describe the ultrastructural features of these glands in normal mice and provide quantitative data on the sizes of the acinar cells and their organelles in sham-, oil-, and testosterone-treated castrated mice. Acinar cells in urethral glands from normal mice contain numerous secretory granules, prominent Golgi complexes, elongated mitochondria, and an abundance of rough endoplasmic reticulum (RER) with large and dilated cisternae, all of which are features characteristic of secretory cells. In some acinar cells the cisternae of the RER were filled with closely packed, unbranched, straight, tubular structures that were oriented parallel to one another, that radiated from aggregates of dense material, or that were randomly arranged. In other acinar cells the cisternae of the RER showed a network of branching and anastomosing vesicular-like structures whose limiting membranes were occasionally seen in continuity with the membranes of the RER. Secretory acini showed large, unbranched tubules in the acinar lumen. When cut at right angles the large tubules exhibited a distinct fuzzy outer coat with fine projections radiating outwards. The ultrastructure of the acinar cells and the presence of tubules in the lumen suggests that they are engaged in secretion of a tubular protein. Morphometric analysis of acinar cells in the urethral glands showed that the mean volumes of nuclei, cytoplasm, secretory granules, vacuoles, and mitochondria were significantly reduced in castrated mice in comparison to either normal or testosterone-treated castrated mice. This confirms earlier observations that the urethral glands are targets of testosterone.

  16. Involvement of Renin-Angiotensin System in Damage of Angiotensin-Converting Enzyme Inhibitor Captopril on Bone of Normal Mice.

    Science.gov (United States)

    Liu, Jin-Xin; Wang, Liang; Zhang, Yan

    2015-01-01

    This study was performed to investigate the effect of angiotensin-converting enzyme inhibitor, captopril, on bone metabolism and histology, and the action of captopril on the components of the skeletal renin-angiotensin system (RAS) and bradykinin receptor in normal male mice. The mice were orally administered captopril (10 mg/kg) for 4 weeks with vehicle-treated mice as normal control. The histology of trabecular bone at the distal femoral end was determined by hematoxylin & eosin, Safranin O and Masson-Trichrome staining. The captopril-treated mice showed a decreased level of testosterone (pCaptopril has detrimental effects on trabecular bone as demonstrated by the loss of cancellous bone mass and network connections as well as changes to the chondrocytes zone. The expression of angiotensin-converting enzyme (pcaptopril treatment. Thus, the potential underlying mechanism of the damage of captopril on bone can be attributed the increased activity of local bone RAS and the activation of bradykinin receptor.

  17. Dermatan Sulfate-Free Mice Display Embryological Defects and Are Neonatal Lethal Despite Normal Lymphoid and Non-Lymphoid Organogenesis.

    Directory of Open Access Journals (Sweden)

    Xanthi N Stachtea

    Full Text Available The epimerization of glucuronic acid into iduronic acid adds structural variability to chondroitin/dermatan sulfate polysaccharides. Iduronic acid-containing domains play essential roles in processes such as coagulation, chemokine and morphogen modulation, collagen maturation, and neurite sprouting. Therefore, we generated and characterized, for the first time, mice deficient in dermatan sulfate epimerase 1 and 2, two enzymes uniquely involved in dermatan sulfate biosynthesis. The resulting mice, termed DKO mice, were completely devoid of iduronic acid, and the resulting chondroitin sulfate chains were structurally different from the wild type chains, from which a different protein binding specificity can be expected. As a consequence, a vast majority of the DKO mice died perinatally, with greatly variable phenotypes at birth or late embryological stages such as umbilical hernia, exencephaly and a kinked tail. However, a minority of embryos were histologically unaffected, with apparently normal lung and bone/cartilage features. Interestingly, the binding of the chemokine CXCL13, an important modulator of lymphoid organogenesis, to mouse DKO embryonic fibroblasts was impaired. Nevertheless, the development of the secondary lymphoid organs, including the lymph nodes and spleen, was normal. Altogether, our results indicate an important role of dermatan sulfate in embryological development and perinatal survival.

  18. Distribution of intestinal mast cell proteinase in blood and tissues of normal and Trichinella-infected mice.

    Science.gov (United States)

    Huntley, J F; Gooden, C; Newlands, G F; Mackellar, A; Lammas, D A; Wakelin, D; Tuohy, M; Woodbury, R G; Miller, H R

    1990-01-01

    A sensitive and specific enzyme-linked immunosorbent assay (ELISA) was developed for mouse intestinal mast cell proteinase (IMCP). Specificity was demonstrated by the absence of immunoreactivity with extracts of isolated serosal mast cells (SMC), or with high concentrations (50 micrograms/ml) of the antigenically similar rat mast cell proteinases I or II. The small and large intestines in normal mice were the major sources of IMCP, there being little or no IMCP in non-mucosal tissues. Concentrations of IMCP in normal (non-parasitized) mice were low, but were increased 100-1000-fold intestines of mice infected 10 days earlier with Trichinella spiralis. The kinetic response of secreted IMCP into the blood of mice following infection with T. spiralis was also studied. Systemic release of IMCP coincided with the immune expulsion of adult worms from the intestine, and peak concentrations (9.45 micrograms/ml IMCP) occurred 9 days after infection. The tissue distribution of IMCP, its secretion into blood, and its enteric accumulation during parasite infection, are consistent with a mucosal mast cell (MMC) source for IMCP. The results are discussed in the context of similar findings for rat mast cell proteinase II.

  19. Mice with deficient BK channel function show impaired prepulse inhibition and spatial learning, but normal working and spatial reference memory.

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    Marei Typlt

    Full Text Available Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this model for cognitive testing. Auditory brain stem responses to click stimuli showed no threshold differences between knockout mice and their wild-type littermates. Despite of muscular tremor, reduced grip force, and impaired gait, knockout mice exhibited normal locomotion. These findings allowed for testing of sensorimotor gating using the acoustic startle reflex, as well as of working memory, spatial learning and memory in the Y-maze and the Morris water maze, respectively. Prepulse inhibition on the first day of testing was normal, but the knockout mice did not improve over the days of testing as their wild-type littermates did. Spontaneous alternation in the y-maze was normal as well, suggesting that the BK channel knock-out does not impair working memory. In the Morris water maze knock-out mice showed significantly slower acquisition of the task, but normal memory once the task was learned. Thus, we propose a crucial role of the BK channels in learning, but not in memory storage or recollection.

  20. Comparative Analysis of Gastrointestinal Microbiota Between Normal and Caudal-Related Homeobox 2 (Cdx2) Transgenic Mice

    OpenAIRE

    Sakamoto, Hirotsugu; Asahara, Takashi; Chonan, Osamu; Yuki, Norikatsu; Mutoh, Hiroyuki; Hayashi, Shunji; Yamamoto, Hironori; Sugano, Kentaro

    2015-01-01

    Background/Aims Caudal-related homeobox 2 (Cdx2) is expressed in the human intestinal metaplastic mucosa and induces intestinal metaplastic mucosa in the Cdx2 transgenic mouse stomach. Atrophic gastritis and intestinal metaplasia commonly lead to gastric achlorhydria, which predisposes the stomach to bacterial overgrowth. In the present study, we determined the differences in gut microbiota between normal and Cdx2 transgenic mice, using quantitative reverse transcription-polymerase chain reac...

  1. Adaptive immune response in JAM-C-deficient mice: normal initiation but reduced IgG memory.

    Science.gov (United States)

    Zimmerli, Claudia; Lee, Boris P L; Palmer, Gaby; Gabay, Cem; Adams, Ralf; Aurrand-Lions, Michel; Imhof, Beat A

    2009-04-15

    We have recently shown that junctional adhesion molecule (JAM)-C-deficient mice have leukocytic pulmonary infiltrates, disturbed neutrophil homeostasis, and increased postnatal mortality. This phenotype was partially rescued when mice were housed in ventilated isolators, suggesting an inability to cope with opportunistic infections. In the present study, we further examined the adaptive immune responses in JAM-C(-/-) mice. We found that murine conventional dendritic cells express in addition to Mac-1 and CD11c also JAM-B as ligand for JAM-C. By in vitro adhesion assay, we show that murine DCs can interact with recombinant JAM-C via Mac-1. However, this interaction does not seem to be necessary for dendritic cell migration and function in vivo, even though JAM-C is highly expressed by lymphatic sinuses of lymph nodes. Nevertheless, upon immunization and boosting with a protein Ag, JAM-C-deficient mice showed decreased persistence of specific circulating Abs although the initial response was normal. Such a phenotype has also been observed in a model of Ag-induced arthritis, showing that specific IgG2a Ab titers are reduced in the serum of JAM-C(-/-) compared with wild-type mice. Taken together, these data suggest that JAM-C deficiency affects the adaptive humoral immune response against pathogens, in addition to the innate immune system.

  2. CCK(1) receptor is essential for normal meal patterning in mice fed high fat diet.

    Science.gov (United States)

    Donovan, Michael J; Paulino, Gabriel; Raybould, Helen E

    2007-12-05

    Cholecystokinin (CCK), released by lipid in the intestine, initiates satiety by acting at cholecystokinin type 1 receptors (CCK(1)Rs) located on vagal afferent nerve terminals located in the wall of the gastrointestinal tract. In the present study, we determined the role of the CCK(1)R in the short term effects of a high fat diet on daily food intake and meal patterns using mice in which the CCK(1)R gene is deleted. CCK(1)R(-/-) and CCK(1)R(+/+) mice were fed isocaloric high fat (HF) or low fat (LF) diets ad libitum for 18 h each day and meal size, meal frequency, intermeal interval, and meal duration were determined. Daily food intake was unaltered by diet in the CCK(1)R(-/-) compared to CCK(1)R(+/+) mice. However, meal size was larger in the CCK(1)R(-/-) mice compared to CCK(1)R(+/+) mice when fed a HF diet, with a concomitant decrease in meal frequency. Meal duration was increased in mice fed HF diet regardless of phenotype. In addition, CCK(1)R(-/-) mice fed a HF diet had a 75% decrease in the time to 1st meal compared to CCK(1)R(+/+) mice following a 6 h fast. These data suggest that lack of the CCK(1)R results in diminished satiation, causing altered meal patterns including larger, less frequent meals when fed a high fat diet. These results suggest that the CCK(1)R is involved in regulating caloric intake on a meal to meal basis, but that other factors are responsible for regulation of daily food intake.

  3. Ischemia-reperfusion injury leads to distinct temporal cardiac remodeling in normal versus diabetic mice.

    Directory of Open Access Journals (Sweden)

    Megumi Eguchi

    Full Text Available Diabetes is associated with higher incidence of myocardial infarction (MI and increased propensity for subsequent events post-MI. Here we conducted a temporal analysis of the influence of diabetes on cardiac dysfunction and remodeling after ischemia reperfusion (IR injury in mice. Diabetes was induced using streptozotocin and IR performed by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for up to 42 days. We first evaluated changes in cardiac function using echocardiography after 24 hours reperfusion and observed IR injury significantly decreased the systolic function, such as ejection fraction, fractional shortening and end systolic left ventricular volume (LVESV in both control and diabetic mice. The longitudinal systolic and diastolic strain rate were altered after IR, but there were no significant differences between diabetic mice and controls. However, a reduced ability to metabolize glucose was observed in the diabetic animals as determined by PET-CT scanning using 2-deoxy-2-((18Ffluoro-D-glucose. Interestingly, after 24 hours reperfusion diabetic mice showed a reduced infarct size and less apoptosis indicated by TUNEL analysis in heart sections. This may be explained by increased levels of autophagy detected in diabetic mice hearts. Similar increases in IR-induced macrophage infiltration detected by CD68 staining indicated no change in inflammation between control and diabetic mice. Over time, control mice subjected to IR developed mild left ventricular dilation whereas diabetic mice exhibited a decrease in both end diastolic left ventricular volume and LVESV with a decreased intraventricular space and thicker left ventricular wall, indicating concentric hypertrophy. This was associated with marked increases in fibrosis, indicted by Masson trichrome staining, of heart sections in diabetic IR group. In summary, we demonstrate that diabetes principally influences distinct IR-induced chronic changes

  4. Glycinergic synaptic transmission in the cochlear nucleus of mice with normal hearing and age-related hearing loss.

    Science.gov (United States)

    Xie, Ruili; Manis, Paul B

    2013-10-01

    The principal inhibitory neurotransmitter in the mammalian cochlear nucleus (CN) is glycine. During age-related hearing loss (AHL), glycinergic inhibition becomes weaker in CN. However, it is unclear what aspects of glycinergic transmission are responsible for weaker inhibition with AHL. We examined glycinergic transmission onto bushy cells of the anteroventral CN in normal-hearing CBA/CaJ mice and in DBA/2J mice, a strain that exhibits an early onset AHL. Glycinergic synaptic transmission was examined in brain slices of mice at 10-15 postnatal days old, 20-35 days old, and at 6-7 mo old. Spontaneous inhibitory postsynaptic current (sIPSC) event frequency and amplitude were the same among all three ages in both strains of mice. However, the amplitudes of IPSCs evoked (eIPSC) from stimulating the dorsal CN were smaller, and the failure rate was higher, with increasing age due to decreased quantal content in both mouse strains, independent of hearing status. The coefficient of variation of the eIPSC amplitude also increased with age. The decay time constant (τ) of sIPSCs and eIPSCs were constant in CBA/CaJ mice at all ages, but were significantly slower in DBA/2J mice at postnatal days 20-35, following the onset of AHL, and not at earlier or later ages. Our results suggest that glycinergic inhibition at the synapses onto bushy cells becomes weaker and less reliable with age through changes in release. However, the hearing loss in DBA/2J mice is accompanied by a transiently enhanced inhibition, which could disrupt the balance of excitation and inhibition.

  5. Vascular endothelium derived endothelin-1 is required for normal heart function after chronic pressure overload in mice.

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    Susi Heiden

    Full Text Available BACKGROUND: Endothelin-1 participates in the pathophysiology of heart failure. The reasons for the lack of beneficial effect of endothelin antagonists in heart failure patients remain however speculative. The anti-apoptotic properties of ET-1 on cardiomyocytes could be a reasonable explanation. We therefore hypothesized that blocking the pro-apoptotic TNF-α pathway using pentoxifylline could prevent the deleterious effect of the lack of ET-1 in a model for heart failure. METHODS: We performed transaortic constriction (TAC in vascular endothelial cells specific ET-1 deficient (VEETKO and wild type (WT mice (n = 5-9 and treated them with pentoxifylline for twelve weeks. RESULTS: TAC induced a cardiac hypertrophy in VEETKO and WT mice but a reduction of fractional shortening could be detected by echocardiography in VEETKO mice only. Cardiomyocyte diameter was significantly increased by TAC in VEETKO mice only. Pentoxifylline treatment prevented cardiac hypertrophy and reduction of fractional shortening in VEETKO mice but decreased fractional shortening in WT mice. Collagen deposition and number of apoptotic cells remained stable between the groups as did TNF-α, caspase-3 and caspase-8 messenger RNA expression levels. TAC surgery enhanced ANP, BNP and bcl2 expression. Pentoxifylline treatment reduced expression levels of BNP, bcl2 and bax. CONCLUSIONS: Lack of endothelial ET-1 worsened the impact of TAC-induced pressure overload on cardiac function, indicating the crucial role of ET-1 for normal cardiac function under stress. Moreover, we put in light a TNF-α-independent beneficial effect of pentoxifylline in the VEETKO mice suggesting a therapeutic potential for pentoxifylline in a subpopulation of heart failure patients at higher risk.

  6. Construction of a hepatic stellate cells subtracted cDNA library of differentially expressed genes in normal mice and mice with Schistosomiasis japonica

    Institute of Scientific and Technical Information of China (English)

    Zheng Min; Wu Yi-jun; Cai Wei-min; Weng Hong-lei; Liu Rong-hua

    2005-01-01

    To construct a hepatic stellate cells (HSCs) subtracted cDNA library to find differentially expressed genes in normal mice and mice infected with Schistosomajaponicum (S. japonicum). Suppression subtractive hybridization (SSH) was used. The cDNA fragments of normal mouse were compared to those of schistosoma-infected mice to find differentially expressed genes.Then differentially expressed cDNA fragments were directly inserted into T/A cloning vector to set up the subtractive library.Amplification of the library was carried out with transformation of DH5α. The amplified library contained more than 400 positive bacterial clones, which were then hybridized with forward and backward subtracted probes for differential screening. One hundred positive bacterial clones were randomly selected for sequencing and BLAST analysis. Finally, virtual Northern Blot confirmed such differential expression. The subtracted cDNA library of differentially expressed genes of HSCs was constructed successfully,the library is efficient and lays foundation for screening and cloning new and specific genes of schistosomiasis.

  7. Congenic Mesenchymal Stem Cell Therapy Reverses Hyperglycemia in Experimental Type 1 Diabetes

    OpenAIRE

    2010-01-01

    OBJECTIVE A number of clinical trials are underway to test whether mesenchymal stem cells (MSCs) are effective in treating various diseases, including type 1 diabetes. Although this cell therapy holds great promise, the optimal source of MSCs has yet to be determined with respect to major histocompatibility complex matching. Here, we examine this question by testing the ability of congenic MSCs, obtained from the NOR mouse strain, to reverse recent-onset type 1 diabetes in NOD mice, as well a...

  8. Lepidium meyenii (Maca increases litter size in normal adult female mice

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    Gasco Manuel

    2005-05-01

    Full Text Available Abstract Background Lepidium meyenii, known as Maca, grows exclusively in the Peruvian Andes over 4000 m altitude. It has been used traditionally to increase fertility. Previous scientific studies have demonstrated that Maca increases spermatogenesis and epididymal sperm count. The present study was aimed to investigate the effects of Maca on several fertility parameters of female mice at reproductive age. Methods Adult female Balb/C mice were divided at random into three main groups: i Reproductive indexes group, ii Implantation sites group and iii Assessment of uterine weight in ovariectomized mice. Animals received an aqueous extract of lyophilized Yellow Maca (1 g/Kg BW or vehicle orally as treatment. In the fertility indexes study, animals received the treatment before, during and after gestation. The fertility index, gestation index, post-natal viability index, weaning viability index and sex ratio were calculated. Sexual maturation was evaluated in the female pups by the vaginal opening (VO day. In the implantation study, females were checked for implantation sites at gestation day 7 and the embryos were counted. In ovariectomized mice, the uterine weight was recorded at the end of treatment. Results Implantation sites were similar in mice treated with Maca and in controls. All reproductive indexes were similar in both groups of treatment. The number of pups per dam at birth and at postnatal day 4 was significantly higher in the group treated with Maca. VO day occurred earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized mice, the treatment with Maca increased significantly the uterine weights in comparison to their respective control group. Conclusion Administration of aqueous extract of Yellow Maca to adult female mice increases the litter size. Moreover, this treatment increases the uterine weight in ovariectomized animals. Our study confirms for the first time some of the traditional uses of Maca to

  9. Fish oil promotes survival and protects against cognitive decline in severely undernourished mice by normalizing satiety signals.

    Science.gov (United States)

    Avraham, Yosefa; Saidian, Mayer; Burston, James J; Mevorach, Raphael; Vorobiev, Lia; Magen, Iddo; Kunkes, Eithan; Borges, Beatriz; Lichtman, Aron H; Berry, Elliot M

    2011-08-01

    Severe malnutrition resulting from anorexia nervosa or involuntary starvation leads to low weight, cognitive deficits and increased mortality rates. In the present study, we examined whether fish oil supplementation, compared with that of canola oil, would ameliorate the morbidity and mortality associated with these conditions by normalizing endocannabinoid and monoaminergic systems as well as other systems involved in satiety and cognitive function within the hypothalamus and hippocampus. Female Sabra mice restricted to 40% of their daily food intake exhibited decreased body weight, were sickly in appearance, displayed cognitive deficits and had increased mortality rates. Strikingly, fish oil supplementation that contains high omega-3 fatty acids levels decreased mortality and morbidity, and normalized the expression of genes and neurotransmitters in the hippocampus and hypothalamus. Fish oil supplementation, but not canola oil, increased survival rates, improved general appearance and prevented cognitive decline, despite the facts that both diets contained an equivalent number of calories and that there were no differences in weight between mice maintained on the two diets in 100% but decrease in the 40%. In the hypothalamus, the beneficial effects of fish oil supplementation were related to normalization of the endocannabinoid 2-arachidonylglycerol, serotonin (5-HT) (Pbrain-derived neurotrophic factor. In conclusion, dietary supplements of fish oil, as source of omega-3 fatty acids, may alleviate cognitive impairments associated with severe diet restriction and prolong survival independently of weight gain by normalizing neurochemical systems. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Humoral immunodepression following acute NO/sub 2/ exposure in normal and adrenalectomized mice

    Energy Technology Data Exchange (ETDEWEB)

    Azoulay-Dupuis, E.; Levacher, M.; Muffat-Joly, M.; Pocidalo, J.J.

    1985-01-01

    The effects following 20 ppm NO/sub 2/ exposure on humoral immunity were investigated in C57BI/6 mice after 48, 72, and 96 h exposure. Both spleen plaque-forming cell (PFC) responses and serum hemagglutinins (HA) using sheep red blood cells (SRBC) as antigen were studied. Splenic and thymic weight and cellularity decreased on acute exposure to NO/sub 2/. PFC were markedly depressed after 48 h exposure and continued to decrease as exposure time was lengthened. HA titers were also depressed. The same significant suppression of PFC and HA titers was observed in adrenalectomized mice after 96 h NO/sub 2/ exposure. The depression of humoral immunity in NO/sub 2/-exposed mice was independent of stress-induced endogeneous steroids.

  11. Renal Denervation Normalizes Arterial Pressure With No Effect on Glucose Metabolism or Renal Inflammation in Obese Hypertensive Mice.

    Science.gov (United States)

    Asirvatham-Jeyaraj, Ninitha; Fiege, Jessica K; Han, Ruijun; Foss, Jason; Banek, Christopher T; Burbach, Brandon J; Razzoli, Maria; Bartolomucci, Alessandro; Shimizu, Yoji; Panoskaltsis-Mortari, Angela; Osborn, John W

    2016-10-01

    Hypertension often occurs in concurrence with obesity and diabetes mellitus, commonly referred to as metabolic syndrome. Renal denervation (RDNx) lowers arterial pressure (AP) and improves glucose metabolism in drug-resistant hypertensive patients with high body mass index. In addition, RDNx has been shown to reduce renal inflammation in the mouse model of angiotensin II hypertension. The present study tested the hypothesis that RDNx reduces AP and renal inflammation and improves glucose metabolism in obesity-induced hypertension. Eight-week-old C57BL/6J mice were fed either a low-fat diet (10 kcal%) or a high-fat diet (45 kcal%) for 10 weeks. Body weight, food intake, fasting blood glucose, and glucose metabolism (glucose tolerance test) were measured. In a parallel study, radiotelemeters were implanted in mice for AP measurement. High fat-fed C57BL/6J mice exhibited an inflammatory and metabolic syndrome phenotype, including increased fat mass, increased AP, and hyperglycemia compared with low-fat diet mice. RDNx, but not Sham surgery, normalized AP in high-fat diet mice (115.8±1.5 mm Hg in sham versus 96.6±6.7 mm Hg in RDNx). RDNx had no significant effect on AP in low-fat diet mice. Also, RDNx had no significant effect on glucose metabolism or renal inflammation as measured by the number of CD8, CD4, and T helper cells or levels of inflammatory cytokines in the kidneys. These results indicate that although renal nerves play a role in obesity-induced hypertension, they do not contribute to impaired glucose metabolism or renal inflammation in this model.

  12. Studies on the host-parasite relationship of Schistosoma japonicum in normal and immunosuppressed mice.

    Science.gov (United States)

    Moloney, N A; Doenhoff, M J; Webbe, G; Hinchcliffe, P

    1982-11-01

    Infections of Schistosoma japonicum were studied in mice which were immunosuppressed either by thymectomy and administration of antithymocyte serum or by treatment with hydrocortisone acetate. The relation of S. japonicum with the immunosuppressed host differed with that reported for Schistosoma mansoni. The pathogenesis of the S. japonicum infection in the immunosuppressed host was less severe than that caused by S. mansoni, with respect to survival of, and hepatocellular damage to, the host. In contrast with S. mansoni, S. japonicum did not have a reduced fecundity in immunosuppressed mice and there was no significant reduction in the numbers of faecal eggs excreted by these hosts.

  13. Age Sensitivity of Behavioral Tests and Brain Substrates of Normal Aging in Mice

    OpenAIRE

    Kennard, John A.; Woodruff-Pak, Diana S.

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memo...

  14. Hearts of dystonia musculorum mice display normal morphological and histological features but show signs of cardiac stress.

    Directory of Open Access Journals (Sweden)

    Justin G Boyer

    Full Text Available Dystonin is a giant cytoskeletal protein belonging to the plakin protein family and is believed to crosslink the major filament systems in contractile cells. Previous work has demonstrated skeletal muscle defects in dystonin-deficient dystonia musculorum (dt mice. In this study, we show that the dystonin muscle isoform is localized at the Z-disc, the H zone, the sarcolemma and intercalated discs in cardiac tissue. Based on this localization pattern, we tested whether dystonin-deficiency leads to structural defects in cardiac muscle. Desmin intermediate filament, microfilament, and microtubule subcellular organization appeared normal in dt hearts. Nevertheless, increased transcript levels of atrial natriuretic factor (ANF, 66% beta-myosin heavy chain (beta-MHC, 95% and decreased levels of sarcoplasmic reticulum calcium pump isoform 2A (SERCA2a, 26%, all signs of cardiac muscle stress, were noted in dt hearts. Hearts from two-week old dt mice were assessed for the presence of morphological and histological alterations. Heart to body weight ratios as well as left ventricular wall thickness and left chamber volume measurements were similar between dt and wild-type control mice. Hearts from dt mice also displayed no signs of fibrosis or calcification. Taken together, our data provide new insights into the intricate structure of the sarcomere by situating dystonin in cardiac muscle fibers and suggest that dystonin does not significantly influence the structural organization of cardiac muscle fibers during early postnatal development.

  15. Effects of cortisone on H-2 agglutinin response in normal and thymectomized adult mice

    Science.gov (United States)

    Ramos, Alicia; Chacón, J.; Ferreira, A.; Hoecker, G.

    1973-01-01

    Cortisone suppresses circulating H-2 agglutinins when given prior to the injection of soluble cell extracts but not when the same antigens are given as cells. This same difference in antigen handling is observed in adult cortisone-treated thymectomized mice. Thus thymus as such is not involved in these differences in antigen handling. The spleen of adult thymectomized mice is as sensitive to cortisone as that of intact or sham-operated animals: after a strong initial drop in weight, the spleen recovers even during cortisone treatment in both intact and thymectomized mice. When a second cortisone treatment is given, the spleen loses about the same weight fraction as the first time in thymectomized and intact mice. These findings indicate that a fraction of either thymus or marrow-dependent lymphocytes differentiates in the spleen to become cortisone-sensitive. All these facts taken together show that antigen size per se is the main determining factor in antigen processing, i.e. the cellular path involved in antibody production. PMID:4706562

  16. Delayed cutaneous wound closure in HO-2 deficient mice despite normal HO-1 expression

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Scharstuhl, A.; Cremers, N.A.J.; Pennings, S.W.C.; Paske, J. Te; Rheden, R. van; Breda, C. van Run-van; Regan, R.F.; Russel, F.G.M.; Carels, C.E.L.; Maltha, J.C.; Wagener, F.A.D.T.G.

    2014-01-01

    Impaired wound healing can lead to scarring, and aesthetical and functional problems. The cytoprotective haem oxygenase (HO) enzymes degrade haem into iron, biliverdin and carbon monoxide. HO-1 deficient mice suffer from chronic inflammatory stress and delayed cutaneous wound healing, while corneal

  17. Vestigial-like 2 contributes to normal muscle fiber type distribution in mice.

    Science.gov (United States)

    Honda, Masahiko; Hidaka, Kyoko; Fukada, So-Ichiro; Sugawa, Ryo; Shirai, Manabu; Ikawa, Masahito; Morisaki, Takayuki

    2017-08-02

    Skeletal muscle is composed of heterogeneous populations of myofibers that are classified as slow- and fast-twitch fibers. The muscle fiber-type is regulated in a coordinated fashion by multiple genes, including transcriptional factors and microRNAs (miRNAs). However, players involved in this regulation are not fully elucidated. One of the members of the Vestigial-like factors, Vgll2, is thought to play a pivotal role in TEA domain (TEAD) transcription factor-mediated muscle-specific gene expression because of its restricted expression in skeletal muscles of adult mice. Here, we generated Vgll2 null mice and investigated Vgll2 function in adult skeletal muscles. These mice presented an increased number of fast-twitch type IIb fibers and exhibited a down-regulation of slow type I myosin heavy chain (MyHC) gene, Myh7, which resulted in exercise intolerance. In accordance with the decrease in Myh7, down-regulation of miR-208b, encoded within Myh7 gene and up-regulation of targets of miR-208b, Sox6, Sp3, and Purβ, were observed in Vgll2 deficient mice. Moreover, we detected the physical interaction between Vgll2 and TEAD1/4 in neonatal skeletal muscles. These results suggest that Vgll2 may be both directly and indirectly involved in the programing of slow muscle fibers through the formation of the Vgll2-TEAD complex.

  18. Delayed cutaneous wound closure in HO-2 deficient mice despite normal HO-1 expression

    NARCIS (Netherlands)

    Lundvig, D.M.S.; Scharstuhl, A.; Cremers, N.A.J.; Pennings, S.W.C.; Paske, J. Te; Rheden, R. van; Breda, C. van Run-van; Regan, R.F.; Russel, F.G.M.; Carels, C.E.L.; Maltha, J.C.; Wagener, F.A.D.T.G.

    2014-01-01

    Impaired wound healing can lead to scarring, and aesthetical and functional problems. The cytoprotective haem oxygenase (HO) enzymes degrade haem into iron, biliverdin and carbon monoxide. HO-1 deficient mice suffer from chronic inflammatory stress and delayed cutaneous wound healing, while corneal

  19. Damage of Splenic T Lymphocyte Proliferation and Differentiation and Its Normalization by Electroacupuncture in Morphine-Dependent Mice Mode

    Directory of Open Access Journals (Sweden)

    Hong-Yu Li

    2011-01-01

    Full Text Available In a previous paper we reported that electroacupuncture (EA could suppress opioid withdrawal syndrome and increase the appetite, sleep, and body weight in heroin addicts or morphine dependent animals. Considering that opioids were known to inhibit immune function, the present study was designed to observe whether EA could modulate the immune status of morphine dependent and withdrawal mice. We found that chronic morphine-induced decrease of splenic T lymphocyte proliferation and IL-2 production can be significantly raised by 2 Hz EA, and the fluctuation of CD4+/CD8+ ratio was also run to the baseline level by the EA. These findings indicated that chronic morphine exposure-induced immune dysfunction in mice could be normalized by 2 Hz EA.

  20. Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice.

    Science.gov (United States)

    Xu, Z; Dong, Y; Peng, F; Yu, Z; Zuo, Y; Dai, Z; Chen, Y; Wang, J; Hu, X; Zhou, Q; Ma, H; Bao, Y; Gao, G; Chen, M

    2015-03-01

    This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.

  1. Ultrastructural Localization of Adiponectin protein in Vasculature of Normal and Atherosclerotic mice

    Science.gov (United States)

    Mori, Takuya; Koyama, Yoshihisa; Maeda, Norikazu; Nakamura, Yukiko; Fujishima, Yuya; Matsuda, Keisuke; Funahashi, Tohru; Shimada, Shoichi; Shimomura, Iichiro

    2014-01-01

    Adiponectin, adipose-specific secretory protein, abundantly circulates in bloodstream and its concentration is around 1000-fold higher than that of other cytokines and hormones. Hypoadiponectinemia is a risk factor for atherosclerosis. There is little or no information on ultrastructural localization of adiponectin in the vasculature. Herein we investigated the localization of vascular adiponectin in the aorta using the immunoelectron microscopic technique. In wild-type (WT) mice, adiponectin was mainly detected on the luminal surface membrane of endothelial cells (ECs) and also found intracellularly in the endocytic vesicles of ECs. In the atherosclerotic lesions of apolipoprotein E-knockout (ApoE-KO) mice, adiponectin was detected in ECs, on the cell surface membrane of synthetic smooth muscle cells, and on the surface of monocytes adherent to ECs. Changes in adiponectin localization within the wall of the aorta may provide novel insight into the pathogenesis of atherosclerosis. PMID:24809933

  2. Immunoglobulin G–mediated Inflammatory Responses Develop Normally in Complement-deficient Mice

    Science.gov (United States)

    Sylvestre, Diana; Clynes, Raphael; Ma, Minga; Warren, Henry; Carroll, Michael C.; Ravetch, Jeffrey V.

    1996-01-01

    The role of complement in immunoglobulin G–triggered inflammation was studied in mice genetically deficient in complement components C3 and C4. Using the reverse passive Arthus reaction and experimental models of immune hemolytic anemia and immune thrombocytopenia, we show that these mice have types II and III inflammatory responses that are indistinguishable from those of wild-type animals. Complement-deficient and wild-type animals exhibit comparable levels of erythrophagocytosis and platelet clearance in response to cytotoxic anti–red blood cell and antiplatelet antibodies. Furthermore, in the reverse passive Arthus reaction, soluble immune complexes induce equivalent levels of hemmorhage, edema, and neutrophillic infiltration in complement-deficient and wild-type animals. In contrast, mice that are genetically deficient in the expression of Fc receptors exhibit grossly diminished reactions by both cytotoxic antibodies and soluble immune complexes. These studies provide strong evidence that the activation of cell-based FcγR receptors, but not complement, are required for antibody-triggered murine inflammatory responses. PMID:8976192

  3. Normal Platelet Integrin Function in Mice Lacking Hydrogen Peroxide-Induced Clone-5 (Hic-5.

    Directory of Open Access Journals (Sweden)

    Michael Popp

    Full Text Available Integrin αIIbβ3 plays a central role in the adhesion and aggregation of platelets and thus is essential for hemostasis and thrombosis. Integrin activation requires the transmission of a signal from the small cytoplasmic tails of the α or β subunit to the large extracellular domains resulting in conformational changes of the extracellular domains to enable ligand binding. Hydrogen peroxide-inducible clone-5 (Hic-5, a member of the paxillin family, serves as a focal adhesion adaptor protein associated with αIIbβ3 at its cytoplasmic tails. Previous studies suggested Hic-5 as a novel regulator of integrin αIIbβ3 activation and platelet aggregation in mice. To assess this in more detail, we generated Hic-5-null mice and analyzed activation and aggregation of their platelets in vitro and in vivo. Surprisingly, lack of Hic-5 had no detectable effect on platelet integrin activation and function in vitro and in vivo under all tested conditions. These results indicate that Hic-5 is dispensable for integrin αIIbβ3 activation and consequently for arterial thrombosis and hemostasis in mice.

  4. Partial hepatectomy induces delayed hepatocyte proliferation and normal liver regeneration in ovariectomized mice

    Directory of Open Access Journals (Sweden)

    Umeda M

    2015-07-01

    Full Text Available Makoto Umeda,1 Masaki Hiramoto,1,2 Takeshi Imai1 1Department of Aging Intervention, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan; 2Department of Biochemistry, Tokyo Medical University, Tokyo, Japan Abstract: Estrogens play central roles in sexual development, reproduction, and hepatocyte proliferation. The ovaries are one of the main organs for estradiol (E2 production. Ovariectomies (OVXs were performed on the female mice, and hepatocyte proliferation was analyzed. The ovariectomized mice exhibited delayed hepatocyte proliferation after partial hepatectomy (PH and also exhibited delayed and reduced E2 induction. Both E2 administration and PH induced the gene expression of estrogen receptor α (ERα. The transcripts of ERα were detected specifically in periportal hepatocytes after E2 administration and PH. Moreover, the E2 concentrations and hepatocyte proliferation rates were highest in the proestrus period of the estrous cycle. Taken together, these findings indicate that E2 accelerated ERα expression in periportal hepatocytes and hepatocyte proliferation in the female mice.Keywords: estrogen, ER, estrous cycle, hepatocyte proliferation, liver regeneration

  5. Dietary cholesterol does not normalize low plasma cholesterol levels but induces hyperbilirubinemia and hypercholanemia in Mdr2 P-glycoprotein-deficient mice

    NARCIS (Netherlands)

    Voshol, PJ; Koopen, NR; de Vree, JML; Havinga, R; Princen, HMG; Elferink, RPJO; Groen, AK; Kuipers, F

    Background/Aims: Mdr2 P-glycoprotein deficiency in mice (Mdr2((-/-))) leads to formation of cholesterol/cholesterol-depleted bile and reduced plasma HDL cholesterol. We addressed the questions: (1) does HDL in Mdr2((-/-)) mice normalize upon phospholipid and/or cholesterol feeding, and (2): is the

  6. Pharmacokinetics and tissue distribution of five active ingredients of Eucommiae cortex in normal and ovariectomized mice by UHPLC-MS/MS.

    Science.gov (United States)

    An, Jing; Hu, Fangdi; Wang, Changhong; Zhang, Zijia; Yang, Li; Wang, Zhengtao

    2016-09-01

    1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic. 2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice. 3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0-∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.

  7. Scaffold-Free Coculture Spheroids of Human Colonic Adenocarcinoma Cells and Normal Colonic Fibroblasts Promote Tumorigenicity in Nude Mice

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    Jong-il Park

    2016-02-01

    Full Text Available The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs and normal colonic fibroblasts (NCFs and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.

  8. ASCT2 (SLC1A5)-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production

    Science.gov (United States)

    Masle-Farquhar, Etienne; Bröer, Angelika; Yabas, Mehmet; Enders, Anselm; Bröer, Stefan

    2017-01-01

    SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5’s primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress. These processes are also essential to immune cells, including neutrophils, macrophages, B and T lymphocytes. We show here that mice with a stop codon in Slc1a5 have reduced glutamine uptake in activated lymphocytes and primary fibroblasts. B and T cell populations and maturation in resting mice were not affected by absence of SLC1A5. Antibody production in resting and immunized mice and the germinal center response to immunization were also found to be normal. SLC1A5 has been recently described as a novel target for the treatment of a variety of cancers, and our results indicate that inhibition of SLC1A5 in cancer therapy may be tolerated well by the immune system of cancer patients. PMID:28553292

  9. ASCT2 (SLC1A5-Deficient Mice Have Normal B-Cell Development, Proliferation, and Antibody Production

    Directory of Open Access Journals (Sweden)

    Etienne Masle-Farquhar

    2017-05-01

    Full Text Available SLC1A5 (solute carrier family 1, member 5 is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5’s primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress. These processes are also essential to immune cells, including neutrophils, macrophages, B and T lymphocytes. We show here that mice with a stop codon in Slc1a5 have reduced glutamine uptake in activated lymphocytes and primary fibroblasts. B and T cell populations and maturation in resting mice were not affected by absence of SLC1A5. Antibody production in resting and immunized mice and the germinal center response to immunization were also found to be normal. SLC1A5 has been recently described as a novel target for the treatment of a variety of cancers, and our results indicate that inhibition of SLC1A5 in cancer therapy may be tolerated well by the immune system of cancer patients.

  10. Mice expressing aberrant sperm-specific protein PMIS2 produce normal-looking but fertilization-incompetent spermatozoa.

    Science.gov (United States)

    Yamaguchi, Ryo; Fujihara, Yoshitaka; Ikawa, Masahito; Okabe, Masaru

    2012-07-01

    Eight kinds of gene-disrupted mice (Clgn, Calr3, Pdilt, Tpst2, Ace, Adam1a, Adam2, and Adam3) show impaired sperm transition into the oviducts and defective sperm binding to the zona pellucida. All of these knockout strains are reported to lack or show aberrant expression of a disintegrin and metallopeptidase domain 3 (ADAM3) on the sperm membrane. We performed proteomic analyses of the proteins of these infertile spermatozoa to clarify whether the abnormal function is caused exclusively by a deficiency in ADAM3 expression. Two proteins, named PMIS1 and PMIS2, were missing in spermatozoa from Clgn-disrupted mice. To study their roles, we generated two gene-disrupted mouse lines. Pmis1-knockout mice were fertile, but Pmis2-knockout males were sterile because of a failure of sperm transport into the oviducts. Pmis2-deficient spermatozoa also failed to bind to the zona pellucida. However, they showed normal fertilizing ability when eggs surrounded with cumulus cells were used for in vitro fertilization. Further analysis revealed that these spermatozoa lacked the ADAM3 protein, but the amount of PMIS2 was also severely reduced in Adam3-deficient spermatozoa. These results suggest that PMIS2 might function both as the ultimate factor regulating sperm transport into the oviducts and in modulating sperm-zona binding.

  11. Over-the-counter analgesics normalize blood glucose and body composition in mice fed a high fat diet.

    Science.gov (United States)

    Kendig, Eric L; Schneider, Scott N; Clegg, Deborah J; Genter, Mary Beth; Shertzer, Howard G

    2008-07-15

    Type 2 diabetes (noninsulin-dependent diabetes mellitus) develops from a pre-diabetic condition that is characterized by insulin resistance and glucose intolerance, and is exacerbated by obesity. In this study, we compared the ability of over-the-counter analgesic drugs (OTCAD) [acetaminophen (APAP); ibuprofen (IBU); naproxen (NAP); aspirin (ASA)], to protect against the development of a pre-diabetic state in mice fed a high fat diet. After 10 weeks on the high fat diet, mice had normal fasting blood glucose (FBG) levels, but exhibited impaired glucose tolerance. Treatment with 20 mg OTCADs/kg body weight improved glucose tolerance, with the order of efficacy, APAP=ASA>IBU, while NAP proved ineffective. Mice fed the high fat diet also exhibited increases in weight gain associated with an increase in body fat. OTCADs prevented in part this increase in body fat, in the order of efficacy, APAP=IBU>NAP=ASA. In isolated liver mitochondria, OTCADs inhibited succinate-dependent H2O2 production, while in white adipose tissue, APAP inhibited NADPH-oxidase mediated H2O2 production and lipid peroxidation. Thus, OTCADs diminish pro-oxidant processes that might otherwise exacerbate inflammation and a pre-diabetic state. We conclude that OTCADs, especially APAP and IBU, may be valuable tools to delay or prevent the development of type 2 diabetes from a pre-diabetic condition.

  12. Dietary Fructus Schisandrae extracts and fenofibrate regulate the serum/hepatic lipid-profile in normal and hypercholesterolemic mice, with attention to hepatotoxicity

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    Pan Si-Yuan

    2012-09-01

    Full Text Available Abstract Background Schisandra, a globally distributed plant, has been widely applied to health care products. Here, we investigated the effects of dietary intake of Fructus Schisandrae chinensis (FSC, both aqueous and ethanolic extracts (AqFSC, EtFSC, on serum/hepatic lipid contents in normal diet (ND- and high-fat/cholesterol/bile salt diet (HFCBD-fed mice. Methods Male ICR mice were fed with ND or HFCBD, supplemented with 1 and 4% of AqFSC and EtFSC, respectively, or 0.1% fenofibrate, for 13 days. Lipids were determined according to the manufacture’s instructions. Results EtFSC, but not AqFSC, significantly elevated hepatic triglyceride (TG in mice fed with ND. Feeding mice with HFCBD increased serum total cholesterol (TC, high density lipoprotein (HDL and low density lipoprotein (LDL levels as well as alanine aminotransferase (ALT activity. Supplementation with AqFSC, EtFSC or fenofibrate significantly reduced hepatic TC and TG levels. However, AqFSC and EtFSC supplementation increased serum HDL and LDL levels in mice fed with HFCBD. Fenofibrate increased serum HDL and reduced serum LDL contents in hypercholesterolemic mice. EtFSC reduced, but fenofibrate elevated, serum ALT activity in both normal and hypercholesterolemic mice. While fenofibrate reduced serum TC, TG, and HDL levels in mice fed with ND, it increased serum HDL and reduced serum LDL and TC levels in mice fed with HFCBD. Hepatomegaly was found in normal and hypercholesterolemic mice fed with diet supplemented with fenofibrate. Conclusions Feeding mice with AqFSC and EtFSC ameliorated the HFCBD-induced hepatic steatosis. In addition, EtFSC may offer protection against hepatic injury in hypercholesterolemic mice.

  13. Elevation of extracellular adenosine enhances haemopoiesis-stimulating effects of G-CSF in normal and gamma-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Hofer, M.; Pospisil, M.; Netikiva, J.; Hola, J. [Institute of Biophysics, Academy of Sciences of the Czech Republic (Czech Republic)

    1997-03-01

    Effects of combined treatment with drugs elevating extracellular adenosine (dipyridamole /DP/, inhibiting the extracellular uptake of adenosine, and adenosine monophosphate /AMP/, an adenosine pro-drug), and G-CSF (granulocyte colony-stimulating factor) on haemopoiesis of normal and gamma-irradiated mice were ascertained. The agents were administered alone or in combination in a 4-day regimen. In normal, unirradiated animals, the haematological endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, i.e., increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC) and morphologically recognizable granulocyte cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of DP plus AMP administrated 30 minutes before G-CSF. Furthermore, it was found that the stimulatory action of DP plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 {mu}g/d). In experiments with irradiated mice, when the 4-day therapeutic regimen was applied on days 3 to 6 following irradiation with the dose of 4 Gy, analogical stimulation of granulopoiesis was observed in the recovery phase on days 14 and 18 after irradiation. As example, see Fig. 1 for counts of granulocyte cells in femoral bone marrow. (authors)

  14. Cytodifferentiation of the postnatal mouse stomach in normal and Huntingtin-interacting protein 1-related-deficient mice

    Science.gov (United States)

    Keeley, Theresa M.

    2010-01-01

    Huntingtin-interacting protein 1-related (Hip1r) is highly expressed in gastric parietal cells, where it participates in vesicular trafficking associated with acid secretion. Hip1r-deficient mice have a progressive remodeling of the mucosa, including apoptotic loss of parietal cells, glandular hypertrophy, mucous cell metaplasia, and reduced numbers of zymogenic cells. In this study, we characterized gastric gland development in wild-type and Hip1r-deficient mice to define normal development, as well as the timing and sequence of the cellular transformation events in the mutant stomach. Postnatal (newborn to 8-wk-old) stomachs were examined by histological and gene expression analysis. At birth, gastric glands in wild-type and mutant mice were rudimentary and mature gastric epithelial cells were not apparent, although marker expression was detected for most cell lineages. Interestingly, newborns exhibited unusual cell types, including a novel surface cell filled with lipid and cells that coexpressed markers of mature mucous neck and zymogenic cells. Glandular morphogenesis proceeded rapidly in both genotypes, with gastric glands formed by weaning at 3 wk of age. In the Hip1r-deficient stomach, epithelial cell remodeling developed in a progressive manner. Initially, in the perinatal stomach, cellular changes were limited to parietal cell apoptosis. Other epithelial cell changes, including apoptotic loss of zymogenic cells and expansion of metaplastic mucous cells, emerged several weeks later when the glands were morphologically mature. Thus, parietal cell loss appeared to be the initiating event in Hip1r-deficient mice, with secondary remodeling of the other gastric epithelial cells. PMID:20813912

  15. Clearance of a monoclonal anti-DNA antibody following administration of DNA in normal and autoimmune mice

    Energy Technology Data Exchange (ETDEWEB)

    Jones, F.S.; Pisetsky, D.S.; Kurlander, R.J.

    1986-04-01

    To study the assembly of DNA-anti-DNA complexes in vivo, we have measured the clearance from blood and organ localization of a murine IgG2a monoclonal anti-DNA antibody, called 6/0, following the infusion of DNA intravenously or intraperitoneally. Intraperitoneal DNA caused a profound acceleration of 6/0 anti-DNA clearance that was dose dependent and demonstrable after the infusion of as little as 1.9 microgram per gram of body weight of single-stranded DNA. The antibody was cleared primarily in the liver without increased deposition in the kidney. Intraperitoneal infusions of DNA also accelerated the clearance of 6/0 in autoimmune MRL-lpr/lpr mice. In contrast, intravenous DNA given in comparable doses caused only a slight increase in 6/0 antibody clearance; this accelerated clearance was seen only at low antigen doses and only during the first 10 min following DNA infusion. Using double-radiolabeling techniques, 6/0 and Cl.18, an IgG2ak myeloma protein without anti-DNA activity, were found to disappear from blood at a comparable rate in both B6D2 mice and MRL-lpr/lpr mice. These results suggest that the DNA-anti-DNA immune complexes can form in vivo but that this process is profoundly affected by the manner in which DNA enters the circulation. In addition, the results suggest that DNA-dependent clearance is not a major pathway for anti-DNA metabolism in normal or at least one strain of autoimmune mice.

  16. B7-H4-Ig treatment of normal mice changes lymphocyte homeostasis and increases the potential of regulatory T cells.

    Science.gov (United States)

    Kristensen, Nanna N; Schmidt, Esben G W; Rasmussen, Susanne; Balk-Møller, Emilie; Claesson, Mogens H

    2013-08-01

    Enteroantigens (eAgs) drive tolerogenic and inflammatory immune responses in the gut and are of importance for sustained immune homeostasis in colonic mucosa. Decline of regulatory activity in the gut mucosa might result in chronic colitis. B7-H4 is a co-inhibitory receptor expressed by professional antigen-presenting cells. By delivering signal 2 during T cell activation, it inhibits T cell proliferation and inflammation. In this study, we have used a newly developed B7-H4-Ig fusion protein and evaluated its effect on eAg-activated effector and regulatory T cells (Treg) in vitro and in vivo. T cells were recovered from the mesenteric lymph nodes (MLNs) of untreated or B7-H4-Ig-treated BALB/c mice. Treatment of cells in vitro did neither affect the proliferation of effector T cells nor the function of Tregs. In vivo, B7-H4 treatment increased the total number of MLN-derived CD4⁺ and CD8⁺ T cell subsets as well as the functional activity of MLN-derived Tregs, whereas the proliferative activity of eAg or alloantigen specific effector T cells was not influenced, although treatment resulted in less secretion of inflammatory cytokines and chemokines from these cells. B7-H4-Ig treatment of severe combined immune-deficient (SCID) mice undergoing T cell transfer colitis did not influence the course of disease probably reflecting the lack of Tregs in this model of chronic colitis. In conclusion, we show that treatment with B7-H4-Ig in vivo changes lymphocyte homeostasis and increases the regulatory potential in normal mice, but does not affect the course of disease development in SCID mice undergoing T cell transfer colitis.

  17. The effect of cortisone on the multiplication of M. tuberculosis in normal and immune mice

    Science.gov (United States)

    Robson, J. M.; Sullivan, F. M.

    1957-01-01

    The multiplication of M. tuberculosis, var. bovis inoculated into the cornea of mice was studied by staining the whole cornea at various stages after inoculation. Four groups of animals were studied: untreated animals, animals treated with cortisone, animals previously immunized with the same bovine strain, and immunized animals treated with cortisone. In the untreated immunized group little or no multiplication occurred. In the other three groups multiplication did occur and was about the same for the first week after inoculation. After this stage, cortisone-treated animals, whether previously immunized or not, showed increased multiplication and massive cord formation, as compared with untreated animals in which little further multiplication was seen. The cortisone treatment had thus completely suppressed immunity. The significance of these results is discussed. ImagesFIG. 1FIG. 2 PMID:13446380

  18. Meta-chlorophenylpiperazine attenuates formalin-induced nociceptive responses through 5-HT1/2 receptors in both normal and diabetic mice.

    Science.gov (United States)

    Takeshita, N; Yamaguchi, I

    1995-12-01

    1. This study was designed to investigate the effect of meta-chlorophenylpiperazine (m-CPP; a 5-hydroxytryptamine (5-HT) receptor agonist) on the formalin-induced nociceptive responses in normal, insulin-dependent streptozotocin (STZ) diabetic and non-insulin dependent genetically diabetic (db/db) mice. 2. A subcutaneous injection of diluted formalin (1% formaldehyde in 0.9% saline, 10 microliters) under the plantar surface of the left hindpaw induced biphasic nociceptive responses, the first and second phases considered to represent acute and chronic pain, respectively. The former response in db/db mice was significantly lower than those in normal mice, and the latter responses in STZ and db/db mice were significantly lower than those in normal mice. 3. In normal mice, m-CPP (0.32-3.2 mg ml-1, p.o.) exhibited potent antinociceptive activity, dose-dependently attenuating the first and second phase; the ID50 value of the second phase was 0.4 mg kg-1. m-CPP (0.32-3.2 mg kg-1, p.o.) also dose-dependently attenuated the formalin-induced nociceptive responses in STZ-induced diabetic mice and genetically diabetic db/db mice, and the activities were comparable to those in normal mice. 4. The antinociceptive activities of m-CPP (1 mg kg-1, p.o.) were significantly inhibited by pretreatment with pindolol (a 5-HT1-receptor antagonist, 1 mg kg-1, i.p.) or ketanserin (a 5-HT2 receptor antagonist, 1 mg kg-1, i.p.) but were hardly affected by ICS205-930 (a 5-HT3 receptor antagonist, 1 mg kg-1, i.p.). 5. These results suggest that m-CPP inhibits not only acute but also chronic pain transmission through 5-HT1 and 5-HT2 receptors, and that the 5-hydroxytryptaminergic antinociceptive pathways are little affected by diabetes.

  19. Introducing DartMouse: The Mouse Speed Congenic Facility at Dartmouth Medical School

    Science.gov (United States)

    Trask, H.; Tomlinson, C.; Fiering, S.; Gorham, J.D.; Muirhead, K.

    2010-01-01

    CF-9 DartMouse™ is the Mouse Speed Congenic Facility at Dartmouth Medical School. Use of DartMouse allows for the rapid introgression of modified genes onto any inbred strain of mouse. Speed congenic strains of mice are achievable in 5 generations (1 to 1.5 years), versus 10 generations (∼3 years) required by conventional back-crossing. The application of DartMouse services saves both money and time for researchers using the laboratory mouse for any number of pre-clinical disease models. DartMouse is a complete service facility that works closely with clients at and outside of Dartmouth, helping to design appropriate breeding schemes to optimize back-crossing speed and efficiency. Clients supply mouse tail snips. DartMouse isolates genomic DNA, performs and analyzes complete genome-wide scans, and returns data in graphical and spreadsheet formats. DartMouse discusses results with clients and makes specific recommendations on breeder selection. DartMouse uses “SNP-Chip” technology on an Illumina BeadStation 500 Platform. Chips use a 377 SNP array covering the mouse genome with an average interval density of <7 cM. Turnaround time from receipt of tails to results is typically <2 weeks. One of DartMouse's most popular services is the “background check” in which the genetic background of supposedly fully back-crossed mice can be thoroughly assessed across all chromosomes. DartMouse was inaugurated in the summer of 2008, and received ARRA-funding in the fall of 2009. Our plans are to make DartMouse a regional and national core facility for the generation of speed congenic mice and for the verification of genetic background for conventionally back-crossed mice.

  20. Normal hematopoiesis and lack of β-catenin activation in osteoblasts of patients and mice harboring Lrp5 gain-of-function mutations

    DEFF Research Database (Denmark)

    Galán-Díez, Marta; Isa, Adiba; Ponzetti, Marco;

    2016-01-01

    of hematopoiesis and leukemogenic properties of β-catenin activation in osteoblasts, that lead to development of acute myeloid leukemia (AML). Using mice with gain-of-function (GOF) Lrp5 alleles (Lrp5(A214V)) that recapitulate the human high bone mass (HBM) phenotype, as well as patients with the T253I HBM Lrp5...... patients showed normal hematopoiesis, normal percentage of myeloid cells, and lack of anemia. We conclude that Lrp5 GOF mutations do not activate β-catenin signaling in osteoblasts. As a result, myeloid lineage differentiation is normal in HBM patients and mice. This article is part of a Special Issue...

  1. CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis

    DEFF Research Database (Denmark)

    Gad, M; Brimnes, J; Claesson, Mogens Helweg

    2003-01-01

    Adoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina propria (LP), express an activated Th1 phenotype and proliferate vigorously when exposed ex vivo to enteric bacterial antigens. As LP CD4......+ T cells from normal BALB/c mice do not respond to enteric bacterial antigens, we have investigated whether colonic LP-derived CD4+ T cells from normal mice suppress the antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived CD4+ T cells cocultured with bone marrow......-derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10...

  2. Cell lineage relationship in the stomach of normal and genetically manipulated mice

    Directory of Open Access Journals (Sweden)

    S.M. Karam

    1998-02-01

    Full Text Available The oxyntic mucosa of the mouse stomach is lined with a heterogeneous population of cells that form numerous short pits continuous with long tubular glands. Tritiated thymidine radioautography has made it possible to pinpoint the origin of all cell types and to follow the differentiation/migration of different cell lineages along the pit-gland unit. The proliferating multipotent stem cells functionally anchored in the upper glandular region, the isthmus, give rise to three main lineage precursors: 1 pre-pit cells, which migrate upward to the pit while differentiating into mucus-producing pit cells; 2 pre-neck cells, which migrate downward to the glandular neck while differentiating into mucus-producing neck cells that, by approaching the glandular base, gradually change their phenotype into pepsinogen- and intrinsic factor-producing zymogenic cells; 3 pre-parietal cells, which differentiate into acid-producing parietal cells in the isthmus and then undergo bipolar migration towards the pit and the glandular base. Thus, parietal cells are the only cells that complete their differentiation in the isthmus and then migrate to be scattered throughout the pit-gland unit. To determine whether parietal cells play a role in controlling decisions about cell fate within the pit-gland unit, the gastric epithelium has been examined in transgenic mice expressing the H,K-ATPase ß-subunit-1035 to +24/simian virus 40 large T antigen fusion gene. The blockade in parietal cell differentiation in these mice produces an amplification of lineage precursors, a marked depletion of zymogenic cells and an increase in pit cell census. Ablation of parietal cells in another transgenic mouse model expressing the H,K-ATPase ß-subunit-1035 to +24/diphtheria toxin fragment A fusion gene also produces amplification of lineage precursors, and similar effects on zymogenic and pit cell census. These findings strongly suggest that parietal cells produce regulatory signals that

  3. Laser Therapy Inhibits Tumor Growth in Mice by Promoting Immune Surveillance and Vessel Normalization

    Directory of Open Access Journals (Sweden)

    Giulia Ottaviani

    2016-09-01

    Full Text Available Laser therapy, recently renamed as photobiomodulation, stands as a promising supportive treatment for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. Here we explored the anti-cancer effect of 3 laser protocols, set at the most commonly used wavelengths, in B16F10 melanoma and oral carcinogenesis mouse models. While laser light increased cell metabolism in cultured cells, the in vivo outcome was reduced tumor progression. This striking, unexpected result, was paralleled by the recruitment of immune cells, in particular T lymphocytes and dendritic cells, which secreted type I interferons. Laser light also reduced the number of highly angiogenic macrophages within the tumor mass and promoted vessel normalization, an emerging strategy to control tumor progression. Collectively, these results set photobiomodulation as a safety procedure in oncological patients and open the way to its innovative use for cancer therapy.

  4. Ulcerative dermatitis in C57BL/6 mice exhibits an oxidative stress response consistent with normal wound healing.

    Science.gov (United States)

    Williams, Lisa K; Csaki, Lauren S; Cantor, Rita M; Reue, Karen; Lawson, Greg W

    2012-06-01

    Ulcerative dermatitis (UD) is a common syndrome of unknown etiology that results in profound morbidity in C57BL/6 mice and lines on a C57BL/6 background. The lesions are due to severe pruritus-induced self-trauma, progressing from superficial excoriations to deep ulcerations. UD may be behavioral in origin, with ulcerative lesions resulting from self-mutilating behavior in response to unresolved inflammation or compulsion. Alternatively, abnormal oxidative damage may be a mechanism underlying UD. To evaluate whether UD behaves similarly to normal wounds, consistent with a secondary self-inflicted lesion, or is a distinct disorder with abnormal wound response, we evaluated expression levels of genes representing various arms of the oxidative stress response pathway UD-affected and unwounded C57BL/6J mice. No evidence indicated that UD wounds have a defect in the oxidative stress response. Our findings are consistent with an understanding of C57BL/6 UD lesions as typical rather than atypical wounds.

  5. Optogenetic stimulation of glutamatergic neuronal activity in the striatum enhances neurogenesis in the subventricular zone of normal and stroke mice.

    Science.gov (United States)

    Song, Mingke; Yu, Shan Ping; Mohamad, Osama; Cao, Wenyuan; Wei, Zheng Zachory; Gu, Xiaohuan; Jiang, Michael Qize; Wei, Ling

    2017-02-01

    Neurogenesis in the subventricular zone (SVZ) of the adult brain may contribute to tissue repair after brain injuries. Whether SVZ neurogenesis can be upregulated by specific neuronal activity in vivo and promote functional recovery after stroke is largely unknown. Using the spatial and cell type specific optogenetic technique combined with multiple approaches of in vitro, ex vivo and in vivo examinations, we tested the hypothesis that glutamatergic activation in the striatum could upregulate SVZ neurogenesis in the normal and ischemic brain. In transgenic mice expressing the light-gated channelrhodopsin-2 (ChR2) channel in glutamatergic neurons, optogenetic stimulation of the glutamatergic activity in the striatum triggered glutamate release into SVZ region, evoked membrane currents, Ca(2+) influx and increased proliferation of SVZ neuroblasts, mediated by AMPA receptor activation. In ChR2 transgenic mice subjected to focal ischemic stroke, optogenetic stimuli to the striatum started 5days after stroke for 8days not only promoted cell proliferation but also the migration of SVZ neuroblasts into the peri-infarct cortex with increased neuronal differentiation and improved long-term functional recovery. These data provide the first morphological and functional evidence showing a unique striatum-SVZ neuronal regulation via a semi-phasic synaptic mechanism that can boost neurogenic cascades and stroke recovery. The benefits from stimulating endogenous glutamatergic activity suggest a novel regenerative strategy after ischemic stroke and other brain injuries.

  6. δ-Opioid receptor activation stimulates normal diet intake but conversely suppresses high-fat diet intake in mice.

    Science.gov (United States)

    Kaneko, Kentaro; Mizushige, Takafumi; Miyazaki, Yuri; Lazarus, Michael; Urade, Yoshihiro; Yoshikawa, Masaaki; Kanamoto, Ryuhei; Ohinata, Kousaku

    2014-02-15

    The central opioid system is involved in a broadly distributed neural network that regulates food intake. Here, we show that activation of central δ-opioid receptor not only stimulated normal diet intake but conversely suppressed high-fat diet intake as well. [D-Pen(2,5)]-enkephalin (DPDPE), an agonist selective for the δ-receptor, increased normal diet intake after central administration to nonfasted male mice. The orexigenic activity of DPDPE was inhibited by blockade of cyclooxygenase (COX)-2, lipocalin-type prostaglandin D synthase (L-PGDS), D-type prostanoid receptor 1 (DP(1)), and neuropeptide Y (NPY) receptor type 1 (Y1) for PGD(2) and NPY, respectively, suggesting that this was mediated by the PGD(2)-NPY system. In contrast, DPDPE decreased high-fat diet intake in mice fed a high-fat diet. DPDPE-induced suppression of high-fat diet intake was blocked by antagonists of melanocortin 4 (MC(4)) and corticotropin-releasing factor (CRF) receptors but not by knockout of the L-PGDS gene. These results suggest that central δ-opioid receptor activation suppresses high-fat diet intake via the MC-CRF system, independent of the orexigenic PGD(2) system. Furthermore, orally administered rubiscolin-6, an opioid peptide derived from spinach Rubisco, suppressed high-fat diet intake. This suppression was also blocked by centrally administered naltrindole, an antagonist for the δ-receptor, suggesting that rubiscolin-6 suppressed high-fat diet intake via activation of central δ-opioid receptor.

  7. The Monoclonal Antitoxin Antibodies (Actoxumab–Bezlotoxumab) Treatment Facilitates Normalization of the Gut Microbiota of Mice with Clostridium difficile Infection

    Science.gov (United States)

    Džunková, Mária; D'Auria, Giuseppe; Xu, Hua; Huang, Jun; Duan, Yinghua; Moya, Andrés; Kelly, Ciarán P.; Chen, Xinhua

    2016-01-01

    detected by the end of the experiments. In conclusion, MK-3415A (actoxumab–bezlotoxumab) treatment facilitates normalization of the gut microbiota in CDI mice. It remains to be examined whether or not the prevention of recurrent CDI by the antitoxin antibodies observed in clinical trials occurs through modulation of microbiota. PMID:27757389

  8. The monoclonal antitoxin antibodies (actoxumab-bezlotoxumab treatment facilitates normalization of the gut microbiota of mice with Clostridium difficile infection

    Directory of Open Access Journals (Sweden)

    Mária Džunková

    2016-10-01

    detected by the end of the experiments. In conclusion, MK-3415A (actoxumab-bezlotoxumab treatment facilitates normalization of the gut microbiota in CDI mice. It remains to be examined whether or not the prevention of recurrent CDI by the antitoxin antibodies observed in clinical trials occurs through modulation of microbiota.

  9. Characterization of adult ghrelin and ghrelin receptor knockout mice under positive and negative energy balance.

    Science.gov (United States)

    Sun, Yuxiang; Butte, Nancy F; Garcia, Jose M; Smith, Roy G

    2008-02-01

    Ghrelin and the ghrelin receptor (GH secretagogue receptor, GHS-R), are believed to have important roles in energy homeostasis. We describe results from the first studies to be conducted in congenic (N10) adult ghrelin(-/-) and Ghsr(-/-) mice under conditions of both positive (high-fat diet) and negative (caloric restriction) energy balance. In contrast to results from young N2 mutant mice, changes in body weight and energy expenditure are not clearly distinguishable across genotypes. Although respiratory quotient was lower in mice fed a high-fat diet, no differences were evident between littermate wild-type and null genotypes. With normal chow, a modest decrease trend in respiratory quotient was detected in ghrelin(-/-) mice but not in Ghsr(-/-) mice. Under caloric restriction, the weight loss of ghrelin(-/-) and Ghsr(-/-) mice was identical to wild-type littermates, but blood glucose levels were significantly lower. We conclude that adult congenic ghrelin(-/-) and Ghsr(-/-) mice are not resistant to diet-induced obesity but under conditions of negative energy balance show impairment in maintaining glucose homeostasis. These results support our hypothesis that the primary metabolic function of ghrelin in adult mice is to modulate glucose sensing and insulin sensitivity, rather than directly regulate energy intake and energy expenditure.

  10. Excessive Vitamin E Intake Does Not Cause Bone Loss in Male or Ovariectomized Female Mice Fed Normal or High-Fat Diets.

    Science.gov (United States)

    Ikegami, Hiroko; Kawawa, Rie; Ichi, Ikuyo; Ishikawa, Tomoko; Koike, Taisuke; Aoki, Yoshinori; Fujiwara, Yoko

    2017-10-01

    Background: Animal studies on the effects of vitamin E on bone health have yielded conflicting and inconclusive results, and to our knowledge, no studies have addressed the effect of vitamin E on bone in animals consuming a high-fat diet (HFD).Objective: This study aimed to evaluate the effect of excessive vitamin E on bone metabolism in normal male mice and ovariectomized female mice fed a normal diet (ND) or HFD.Methods: In the first 2 experiments, 7-wk-old male mice were fed an ND (16% energy from fat) containing 75 (control), 0 (vitamin E-free), or 1000 (high vitamin E) mg vitamin E/kg (experiment 1) or an HFD (46% energy from fat) containing 0, 200, 500, or 1000 mg vitamin E/kg (experiment 2) for 18 wk. In the third experiment, 7-wk-old sham-operated or ovariectomized female mice were fed the ND (75 mg vitamin E/kg) or HFD containing 0 or 1000 mg vitamin E/kg for 8 wk. At the end of the feeding period, blood and femurs were collected to measure bone turnover markers and analyze histology and microcomputed tomography.Results: In experiments 1 and 2, vitamin E intake had no effect on plasma alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) activity, or bone formation, resorption, or volume in femurs in mice fed the ND or HFDs. In experiment 3, bone volume was significantly reduced (85%) in ovariectomized mice compared with that in sham-operated mice (P loss in normal male mice or in ovariectomized or sham-operated female mice, regardless of dietary fat content. © 2017 American Society for Nutrition.

  11. HOMER2, a stereociliary scaffolding protein, is essential for normal hearing in humans and mice.

    Directory of Open Access Journals (Sweden)

    Hela Azaiez

    2015-03-01

    Full Text Available Hereditary hearing loss is a clinically and genetically heterogeneous disorder. More than 80 genes have been implicated to date, and with the advent of targeted genomic enrichment and massively parallel sequencing (TGE+MPS the rate of novel deafness-gene identification has accelerated. Here we report a family segregating post-lingual progressive autosomal dominant non-syndromic hearing loss (ADNSHL. After first excluding plausible variants in known deafness-causing genes using TGE+MPS, we completed whole exome sequencing in three hearing-impaired family members. Only a single variant, p.Arg185Pro in HOMER2, segregated with the hearing-loss phenotype in the extended family. This amino acid change alters a highly conserved residue in the coiled-coil domain of HOMER2 that is essential for protein multimerization and the HOMER2-CDC42 interaction. As a scaffolding protein, HOMER2 is involved in intracellular calcium homeostasis and cytoskeletal organization. Consistent with this function, we found robust expression in stereocilia of hair cells in the murine inner ear and observed that over-expression of mutant p.Pro185 HOMER2 mRNA causes anatomical changes of the inner ear and neuromasts in zebrafish embryos. Furthermore, mouse mutants homozygous for the targeted deletion of Homer2 present with early-onset rapidly progressive hearing loss. These data provide compelling evidence that HOMER2 is required for normal hearing and that its sequence alteration in humans leads to ADNSHL through a dominant-negative mode of action.

  12. Protection of athymic (Nu/Nu BALB/c mice against Plasmodium berghei by splenocytes from normal (Nu/ + BALB/c mice

    Directory of Open Access Journals (Sweden)

    José J. Ferraroni

    1985-12-01

    Full Text Available Athymic BALB/c (Nu/Nu mice died at 7-13 days after inoculation (DAI of Plasmodium berghei NK65, whereas their heterozygous (Nu/+ littermates died at 7-8 DAI. Nude (Nu/Nu mice, reconstituted with 2 x 10(7 splenocytes from uninfected heterozygous (Nu/+ littermates at 20 days before parasite inoculation (DBI, died about 2 days earlier than control nude mice; nude mice reconstituted at 10 or 2 DBI lived 2 to 4 days longer than control nudes; and nude mice reconstituted 2 DAI lived even longer and some survived. These findings indicate that P. berghei NK65 induces at least two T-cell dependent immune phenomena, one suppressive and the other stimulatory. Reconstitution of nude mice with T-cells from BALB/c (Nu/+ mice appeared to reduce or bypass suppressive T-cell activities which allowed the formation of a protective immune response by some of the nude mice.

  13. Spatial organization of bacterial flora in normal and inflamed intestine:A fluorescence in situ hybridization study in mice

    Institute of Scientific and Technical Information of China (English)

    Alexander Swidsinski; Vera Loening-Baucke; Herbert Lochs; Laura P. Hale

    2005-01-01

    AIM: To studythe role of intestinal flora in inflammatory bowel disease (IBD).METHODS: The spatial organization of intestinal flora was investigated in normal mice and in two models of murine colitis using fluorescence in situ hybridization.RESULTS: The murine small intestine was nearly bacteriafree. The normal colonic flora was organized in three distinct compartments (crypt, interlaced, and fecal), each with different bacterial compositions. Crypt bacteria were present in the cecum and proximal colon. The fecal compartment was composed of homogeneously mixed bacterial groups that directly contacted the colonic wall in the cecum but were separated from the proximal colonic wall by a dense interlaced layer. Beginning in the middle colon, a mucus gap of growing thickness physically separated all intestinal bacteria from contact with the epithelium. Colonic inflammation was accompanied with a depletion of bacteria within the fecal compartment, a reduced surface area in which feces had direct contact with the colonic wall, increased thickness and spread of the mucus gap, and massive increases of bacterial concentrations in the crypt and interlaced compartments. Adhesive and infiltrative bacteria were observed in inflamed colon only, with dominant Bacteroides species.CONCLUSION: The proximal and distal colons are functionally different organs with respect to the intestinal flora, representing a bioreactor and a Segregation device.The highly organized structure of the colonic flora, its specific arrangement in different colonic segments, and its specialized response to inflammatory stimuli indicate that the intestinal flora is an innate part of host immunity that is under complex control.

  14. Spatial trends of polybrominated diphenyl ether (PBDE) congeners

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Spatial trends of polybrominated diphenyl ether (PBDE) congeners were analyzed in young of the year bluefish collected along the U.S. Atlantic coastline from...

  15. Assimilation efficiency of PBDE congeners in Chinook salmon.

    Science.gov (United States)

    Dietrich, Joseph P; Strickland, Stacy A; Hutchinson, Greg P; Van Gaest, Ahna L; Krupkin, Alex B; Ylitalo, Gina M; Arkoosh, Mary R

    2015-03-17

    Polybrominated diphenyl ether (PBDE) flame retardants are environmental contaminants that can accumulate in biota. PBDE accumulation in an organism depends on exposure, assimilation efficiency, and elimination/metabolism. Net assimilation efficiency represents the fraction of the contaminant that is retained in the organism after exposure. In the present study, congener-specific estimates of net PBDE assimilation efficiencies were calculated from dietary exposures of juvenile Chinook salmon. The fish were exposed to one to eight PBDE congeners up to 1500 ng total PBDEs/g food. Mean assimilation efficiencies varied from 0.32 to 0.50 for BDE congeners 28, 47, 99, 100, 153, and 154. The assimilation efficiency of BDE49 was significantly greater than 100%, suggesting biotransformation from higher brominated congeners. Whole body concentrations of BDE49 significantly increased with both exposure to increasing concentrations of BDE99 and decreasing fish lipid levels, implying lipid-influenced debromination of BDE99 to BDE49. Excluding BDE49, PBDE assimilation efficiency was not significantly related to the numbers of congeners in the diets, or congener hydrophobicity, but was greater in foods with higher lipid levels. Estimates of PBDE assimilation efficiency can be used in bioaccumulation models to assess threats from PBDE exposure to Chinook salmon health and recovery efforts, as well as to their predators.

  16. An inherent acceleratory effect of insulin on small intestinal transit and its pharmacological characterization in normal mice

    Institute of Scientific and Technical Information of China (English)

    Murali Krishna Reddy Peddyreddy; Steven Aibor Dkhar; Subramanian Ramaswamy; Amrithraj Theophilus Naveen; Deepak Gopal Shewade

    2006-01-01

    AIM: To study an inherent effect of insulin on small intestinal transit and to explore involvement of various systems/mechanisms in normal mice.METHODS: Insulin at the doses of 2 μU/kg, 2 mU/kg,2 U/kg or vehicle was subcutaneously administered to four groups of overnight fasted normal male mice.Blood glucose (BG) levels were measured 2 min before insulin administration and 2 min before sacrificing the animals for the measurement of small intestinal transit (SIT). Charcoal meal was administered (0.3 mL) intragastrically 20 min after insulin administration and animals were sacrificed after 20 min and SIT was determined. For exploration of the various mechanisms involved in insulin-induced effect on SIT, the dose of insulin which can produce a significant acceleration of SIT without altering BG levels was determined.The following drugs, atropine (1 mg/kg), clonidine (0.1 mg/kg), ondansetron (1 mg/kg), naloxone (5mg/kg), verapamil (8 mg/kg) and glibenclamide (10 mg/kg), were administered intravenously 10 min prior to the administration of insulin (2 μU/kg).RESULTS: The lower doses of insulin (2 μU/kg and 2 mU/kg) produced a significant acceleration of SIT from 52.0% to 70.7% and 73.5% without lowering blood glucose levels (P< 0.01), while the highest dose of insulin (2 U/kg) produced a fall in blood glucose levels which was also associated with significant acceleration of SIT (P< 0.01). After pretreatment of insulin (2 μU/kg)group with atropine, insulin could reverse 50% of the inhibition produced by atropine. In clonidine-pretreated group, insulin administration could reverse only 37%of the inhibition produced by clonidine and inhibition of SIT was significant compared with vehicle + insulintreated group, i.e. from 74.7% to 27.7% (P<0.01). In ondansetron-pretreated group, insulin administration could produce only mild acceleration of SIT (23.5%). In naloxone-pretreated group, insulin administration could significantly reverse the inhibition of SIT produced

  17. Study of amplitude frequency spectra of the compound action potentials recorded from normal and M. leprae infected mice using Fourier series analysis.

    Science.gov (United States)

    Vidyasagar, P B; Lokhandwalla, M N; Damle, P S

    1986-01-01

    Compound action potentials recorded from normal and M. leprae infected mice sciatic nerves were analysed in frequency domain using Fourier Series Analysis. Changes in myelinated fibre potentials were detected as early as 2nd post-inoculation month. This technique could be further developed to aid in early diagnosis of leprosy.

  18. Spermatid head elongation with normal nuclear shaping requires ADP-ribosyltransferase PARP11 (ARTD11) in mice.

    Science.gov (United States)

    Meyer-Ficca, Mirella L; Ihara, Motomasa; Bader, Jessica J; Leu, N Adrian; Beneke, Sascha; Meyer, Ralph G

    2015-03-01

    Sperm are highly differentiated cells characterized by their species-specific nuclear shapes and extremely condensed chromatin. Abnormal head shapes represent a form of teratozoospermia that can impair fertilization capacity. This study shows that poly(ADP-ribose) polymerase-11 (ARTD11/PARP11), a member of the ADP-ribosyltransferase (ARTD) family, is expressed preferentially in spermatids undergoing nuclear condensation and differentiation. Deletion of the Parp11 gene results in teratozoospermia and male infertility in mice due to the formation of abnormally shaped fertilization-incompetent sperm, despite normal testis weights and sperm counts. At the subcellular level, PARP11-deficient elongating spermatids reveal structural defects in the nuclear envelope and chromatin detachment associated with abnormal nuclear shaping, suggesting functional relevance of PARP11 for nuclear envelope stability and nuclear reorganization during spermiogenesis. In vitro, PARP11 exhibits mono(ADP-ribosyl)ation activity with the ability to ADP-ribosylate itself. In transfected somatic cells, PARP11 colocalizes with nuclear pore components, such as NUP153. Amino acids Y77, Q86, and R95 in the N-terminal WWE domain, as well as presence of the catalytic domain, are essential for colocalization of PARP11 with the nuclear envelope, but catalytic activity of the protein is not required for colocalization with NUP153. This study demonstrates that PARP11 is a novel enzyme important for proper sperm head shaping and identifies it as a potential factor involved in idiopathic mammalian teratozoospermia.

  19. UPLC-MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice.

    Science.gov (United States)

    Deng, Li; Li, Yongzhi; Zhang, Xinshi; Chen, Bo; Deng, Yulin; Li, Yujuan

    2015-10-10

    A UPLC-MS method was developed for determination of pterostilbene (PTS) in plasma and tissues of mice. PTS was separated on Agilent Zorbax XDB-C18 column (50 × 2.1 mm, 1.8 μm) with gradient mobile phase at the flow rate of 0.2 ml/min. The detection was performed by negative ion electrospray ionization in multiple reaction monitoring mode. The linear calibration curve of PTS in mouse plasma and tissues ranged from 1.0 to 5000 and 0.50 to 500 ng/ml (r(2)>0.9979), respectively, with lowest limits of quantification (LLOQ) were between 0.5 and 2.0 ng/ml, respectively. The accuracy and precision of the assay were satisfactory. The validated method was applied to the study of bioavailability and tissue distribution of PTS in normal and Lewis lung carcinoma (LLC) bearing mice. The bioavailability of PTS (dose 14, 28 and 56 mg/kg) in normal mice were 11.9%, 13.9% and 26.4%, respectively; and the maximum level (82.1 ± 14.2 μg/g) was found in stomach (dose 28 mg/kg). The bioavailability, peak concentration (Cmax), time to peak concentration (Tmax) of PTS in LLC mice was increased compared with normal mice. The results indicated the UPLC-MS method is reliable and bioavailability and tissue distribution of PTS in normal and LLC mice were dramatically different. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice.

    Science.gov (United States)

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Jennifer Michelle; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-04-15

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways.

  1. Exendin-4 improves blood glucose control in both young and aging normal non-diabetic mice, possible contribution of beta cell independent effects.

    Directory of Open Access Journals (Sweden)

    Rongrong Fan

    Full Text Available AIMS: Type 2 diabetes is highly prevalent in the elderly population. Glucagon like Peptide-1 mimetic such as exendin-4 augments post-prandial insulin secretion. However, the potential influence of aging on the therapeutic effects of this peptide has not been well studied. In this study, we examined the glucose regulatory effects of exendin-4 in mice with different ages. METHODS: We treated 3-month and 20 to 22-month old C57/DBA mice with 10 nM/kg exendin-4 for 10 days with measurements of blood glucose and body weight. We performed OGTT and ITT to evaluate the glucose response and insulin sensitivity. Islet morphology and beta cell mass were measured by immuno-staining and beta cell proliferation was evaluated by BrdU incorporation and PCNA staining. Real-time PCR and western blot were used to measure protein changes in the liver tissue after exendin-4 treatment. RESULTS: Exendin-4 treatment improved glycemic control in both 3-month and 20 to 22-month old mice. In both groups of mice, the blood glucose lowering effect was independent of beta cell function as indicated by unchanged beta cell proliferation, insulin secretion or beta cell mass. Moreover, we found that exendin-4 treatment increased hepatic AKT and FOXO1 phosphorylation and inhibited glucose-6-phosphotase (G6P and Phosphoenolpyruvate carboxykinase (PEPCK expression in young mice, but this effect was attenuated in aging mice while the insulin sensitivity showed no change in the young group but significantly improved in aging mice. CONCLUSION: Based on these data, we conclude that the glucose lowering effect of exendin-4 in normal non-diabetic mice was not blunted by aging. We further showed that although there was slight difference in the glucose modulating mechanism of exendin-4 therapy in young and aged mice, the improved glucose control seemed uncorrelated with increased beta cell mass or insulin secretion.

  2. Assessment of the reproductive toxicity of inhalation exposure to ethyl tertiary butyl ether in male mice with normal, low active and inactive ALDH2.

    Science.gov (United States)

    Weng, Zuquan; Ohtani, Katsumi; Suda, Megumi; Yanagiba, Yukie; Kawamoto, Toshihiro; Nakajima, Tamie; Wang, Rui-Sheng

    2014-04-01

    No data are available regarding aldehyde dehydrogenase 2 (ALDH2) polymorphisms related to the reproductive toxicity possibly caused by ethyl tertiary butyl ether (ETBE). In this study, two inhalation experiments were performed in Aldh2 knockout (KO), heterogeneous (HT) and wild type (WT) C57BL/6 male mice exposed to ETBE, and the data about general toxicity, testicular histopathology, sperm head numbers, sperm motility and sperm DNA damage were collected. The results showed that the 13-week exposure to 0, 500, 1,750 and 5,000 ppm ETBE significantly decreased sperm motility and increased levels of sperm DNA strand breaks and 8-hydroxy-deoxyguanosine in both WT and KO mice, the effects were found in 1,750 and 5,000 ppm groups of WT mice, and all of the three exposed groups of KO mice compared to the corresponding control; furthermore, ETBE also caused decrease in the relative weights of testes and epididymides, the slight atrophy of seminiferous tubules of testis and reduction in sperm numbers of KO mice exposed to ≥500 ppm. In the experiment of exposure to lower concentrations of ETBE (0, 50, 200 and 500 ppm) for 9 weeks, the remarkable effects of ETBE on sperm head numbers, sperm motility and sperm DNA damage were further observed in KO and HT mice exposed to 200 ppm ETBE, but not in WT mice. Our findings suggested that only exposure to high concentrations of ETBE might result in reproductive toxicity in mice with normal active ALDH2, while low active and inactive ALDH2 enzyme significantly enhanced the ETBE-induced reproductive toxicity in mice, even exposed to low concentrations of ETBE, mainly due to the accumulation of acetaldehyde as a primary metabolite of ETBE.

  3. Effects of combined dietary supplementation with fenofibrate and Schisandrae Fructus pulp on lipid and glucose levels and liver function in normal and hypercholesterolemic mice

    Directory of Open Access Journals (Sweden)

    Zhu PL

    2015-02-01

    Full Text Available Pei-Li Zhu,1 Si-Yuan Pan,1 Shu-Feng Zhou,2 Yi Zhang,1 Xiao-Yan Wang,1 Nan Sun,1 Zhu-Sheng Chu,1 Zhi-Ling Yu,3 Kam-Ming Ko41Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People’s Republic of China; 4Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People’s Republic of ChinaBackground: Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF, a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb pulp (AqSF-P or an SF-related synthetic analog, bicyclol (BY, on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL mice.Methods: Male mice obtained from the Institute of Cancer Research (ICR were fed on a normal diet (ND or high cholesterol/bile salt (0.5%/0.15%, w/w diet (HCBD containing FF (0.03% or 0.1%, w/w with or without AqSF-P (0.3%-9.0%, based on crude herbal material, w/w or BY (0.025%, w/w for 10 days. Then serum lipid levels and alanine aminotransferase (ALT activity, as well as hepatic triglyceride (TG, total cholesterol (TC, and glucose levels, were measured.Results: Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79% in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67% and in HCBD-fed mice (up to 54%, when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was

  4. Effect of lipids from Erabu sea snake, Laticauda semifasciata, on plasma glucose, insulin, and adipocytokine concentrations of normal and streptozotocin-diabetic mice.

    Science.gov (United States)

    Shirai, Nobuya; Higuchi, Tomoyuki; Suzuki, Hiramitsu; Shimizu, Eiji

    2006-01-01

    To clarify the influence of Erabu sea snake lipid on levels of plasma insulin and adipocyte-derived hormones. Normal male mice (6 months) and streptozotocin-diabetic mice (a single administration, 150 mg/kg i.p.) were fed diets containing 10% fat as either lard or a mixture of 5% lard and 5% sea snake lipid for 4 months. The normal mice on the sea snake lipid diet had a significantly lower plasma glucose concentration (198 +/- 16 mg/dl; 148 +/- 11 mg/dl) than those mice on the lard diet. Although plasma insulin concentrations were not influenced by the dietary fat type, leptin (10 +/- 1 ng/ml; 16 +/- 2 ng/ml) and adiponectin (18 +/- 1 mug/ml; 21 +/- 1 mug/ml) concentrations were significantly higher in the sea snake lipid group than in the lard group. However, these effects of a sea snake lipid intake were not evident in the streptozotocin-diabetic mice. The results suggest that the decrease in plasma glucose following the intake of sea snake lipids could be related to a corresponding increase in leptin and adiponectin level. Copyright (c) 2006 S. Karger AG, Basel.

  5. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

    Directory of Open Access Journals (Sweden)

    Chia-Yu Chang

    2015-01-01

    Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

  6. Administration of exogenous 1,25(OH)2D3 normalizes overactivation of the central renin-angiotensin system in 1α(OH)ase knockout mice.

    Science.gov (United States)

    Zhang, Wei; Chen, Lulu; Zhang, Luqing; Xiao, Ming; Ding, Jiong; Goltzman, David; Miao, Dengshun

    2015-02-19

    Previously, we reported that active vitamin D deficiency in mice causes secondary hypertension and cardiac dysfunction, but the underlying mechanism remains largely unknown. To clarify whether exogenous active vitamin D rescues hypertension by normalizing the altered central renin-angiotensin system (RAS) via an antioxidative stress mechanism, 1-alpha-hydroxylase [1α(OH)ase] knockout mice [1α(OH)ase(-/-)] and their wild-type littermates were fed a normal diet alone or with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], or a high-calcium, high-phosphorus "rescue" diet with or without antioxidant N-acetyl-l-cysteine (NAC) supplementation for 4 weeks. Compared with their wild-type littermates, 1α(OH)ase(-/-)mice had high mean arterial pressure, increased levels of renin, angiotensin II (Ang II), and Ang II type 1 receptor, and increased malondialdehyde levels, but decreased anti-peroxiredoxin I and IV proteins and the antioxidative genes glutathione reductase (Gsr) and glutathione peroxidase 4 (Gpx4) in the brain samples. Except Ang II type 1 receptor, these pathophysiological changes were rescued by exogenous 1,25(OH)2D3 or NAC plus rescue diet, but not by rescue diet alone. We conclude that 1,25(OH)2D3 normalizes the altered central RAS in 1α(OH)ase(-/-)mice, at least partially, through a central antioxidative mechanism.

  7. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to β-adrenergic-induced cardiac hypertrophy.

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    Matthew J Spindler

    Full Text Available BACKGROUND: A-kinase anchoring proteins (AKAPs are scaffolding molecules that coordinate and integrate G-protein signaling events to regulate development, physiology, and disease. One family member, AKAP13, encodes for multiple protein isoforms that contain binding sites for protein kinase A (PKA and D (PKD and an active Rho-guanine nucleotide exchange factor (Rho-GEF domain. In mice, AKAP13 is required for development as null embryos die by embryonic day 10.5 with cardiovascular phenotypes. Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in cell culture. However, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hypertrophy are unknown. METHODOLOGY/PRINCIPAL FINDINGS: To determine if these AKAP13 protein domains are required for development, we used gene-trap events to create mutant mice that lacked the Rho-GEF and/or the protein kinase D-binding domains. Surprisingly, heterozygous matings produced mutant mice at Mendelian ratios that had normal viability and fertility. The adult mutant mice also had normal cardiac structure and electrocardiograms. To determine the role of these domains during β-adrenergic-induced cardiac hypertrophy, we stressed the mice with isoproterenol. We found that heart size was increased similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls. However, the mutant hearts had abnormal cardiac contractility as measured by fractional shortening and ejection fraction. CONCLUSIONS: These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse development, normal cardiac architecture, or β-adrenergic-induced cardiac hypertrophic remodeling. However, these domains regulate aspects of β-adrenergic-induced cardiac hypertrophy.

  8. Loss of normal profilaggrin and filaggrin in flaky tail (ft/ft) mice: an animal model for the filaggrin-deficient skin disease ichthyosis vulgaris.

    Science.gov (United States)

    Presland, R B; Boggess, D; Lewis, S P; Hull, C; Fleckman, P; Sundberg, J P

    2000-12-01

    Flaky tail (gene symbol ft) is an autosomal recessive mutation in mice that results in a dry, flaky skin, and annular tail and paw constrictions in the neonatal period. Previous studies demonstrated that the ft mutation maps to the central region of mouse chromosome 3, in the vicinity of the epidermal differentiation complex, a gene locus that includes many nonkeratin genes expressed in epidermis. In this study we report a detailed characterization of the flaky tail mouse. Affected homozygous ft/ft mice exhibit large, disorganized scales on tail and paw skin, marked attenuation of the epidermal granular layer, mild acanthosis, and orthokeratotic hyperkeratosis. Biochemical analysis demonstrated that ft/ft mice lacked normal high molecular profilaggrin (approximately 500 kDa), and instead expressed a lower molecular weight form of profilaggrin (220 kDa) that is not proteolytically processed to profilaggrin intermediates or filaggrin. Mutant mice lacked the large, irregular F-type keratohyalin granules that contain profilaggrin, and filaggrin was absent from the cornified layers of ft/ft epidermis. The expression of epidermal keratins was unchanged, whereas the cornified envelope proteins involucrin and loricrin were increased in ft/ft epidermis. Cultured ft/ft keratinocytes also synthesized reduced amounts of profilaggrin mRNA and protein, demonstrating that the defect in profilaggrin expression is intrinsic to epidermal cells. These findings demonstrate that flaky tail mice express an abnormal profilaggrin polypeptide that does not form normal keratohyalin F-granules and is not proteolytically processed to filaggrin. We propose that the absence of filaggrin, and in particular the hygroscopic, filaggrin-derived amino acids that are thought to function in epidermal hydration, underlies the dry, scaly skin characteristic of ft/ft mice. This animal model provides a tool for understanding the role of filaggrin in normal epidermal function and may provide insight into

  9. Cardiac-Specific Disruption of GH Receptor Alters Glucose Homeostasis While Maintaining Normal Cardiac Performance in Adult Male Mice.

    Science.gov (United States)

    Jara, Adam; Liu, Xingbo; Sim, Don; Benner, Chance M; Duran-Ortiz, Silvana; Qian, Yanrong; List, Edward O; Berryman, Darlene E; Kim, Jason K; Kopchick, John J

    2016-05-01

    GH is considered necessary for the proper development and maintenance of several tissues, including the heart. Studies conducted in both GH receptor null and bovine GH transgenic mice have demonstrated specific cardiac structural and functional changes. In each of these mouse lines, however, GH-induced signaling is altered systemically, being decreased in GH receptor null mice and increased in bovine GH transgenic mice. Therefore, to clarify the direct effects GH has on cardiac tissue, we developed a tamoxifen-inducible, cardiac-specific GHR disrupted (iC-GHRKO) mouse line. Cardiac GH receptor was disrupted in 4-month-old iC-GHRKO mice to avoid developmental effects due to perinatal GHR gene disruption. Surprisingly, iC-GHRKO mice showed no difference vs controls in baseline or postdobutamine stress test echocardiography measurements, nor did iC-GHRKO mice show differences in longitudinal systolic blood pressure measurements. Interestingly, iC-GHRKO mice had decreased fat mass and improved insulin sensitivity at 6.5 months of age. By 12.5 months of age, however, iC-GHRKO mice no longer had significant decreases in fat mass and had developed glucose intolerance and insulin resistance. Furthermore, investigation via immunoblot analysis demonstrated that iC-GHRKO mice had appreciably decreased insulin stimulated Akt phosphorylation, specifically in heart and liver, but not in epididymal white adipose tissue. These changes were accompanied by a decrease in circulating IGF-1 levels in 12.5-month-old iC-GHRKO mice. These data indicate that whereas the disruption of cardiomyocyte GH-induced signaling in adult mice does not affect cardiac function, it does play a role in systemic glucose homeostasis, in part through modulation of circulating IGF-1.

  10. Effect of a protease inhibitor on the stability of catalase in liver and blood from acatalasemic and normal mice.

    Directory of Open Access Journals (Sweden)

    Suzuki,Kazuhiko

    1991-10-01

    Full Text Available Effects of Gabexate mesilate (GM (([ethyl-4-(6-guanidino hexanoyloxy benzoate] methane sulfonate, a protease inhibitor, on the activities of catalase in liver, erythrocytes and reticulocytes from acatalasemic mice were examined. Preincubation without GM at 37 degrees C for 160 min lowered the catalase activities of liver, erythrocytes and reticulocytes from acatalasemic mice, to 24%, 40% and 10% of the initial levels, respectively. But, preincubation with GM at 37 degrees C for 160 min delayed the rapid decrease in activities of residual catalases in the liver, erythrocytes and reticulocytes of acatalasemic mice to 65%, 93% and 85% of the initial values, respectively. At 20 degrees C or below, no reduction in catalase activity of reticulocytes from acatalasemic mice occurred with or even without GM. At pH 5.0, the decrease in catalase activity of acatalasemic mice was small both in the presence and the absence of GM. In the alkaline range, the reduction in the enzyme activity of the mutant mice without GM was enhanced with increase in pH values up to 8.5. But the presence of GM during preincubation at pH 7.5, retained the catalase activity of acatalasemic mice, to 64% of the activity at pH 6.5. These data suggest that some factors affected by GM, might be responsible for the low stability and activity of catalase in the acatalasemic mice.

  11. Effect of hormone treatment on spontaneous and radiation-induced chromosomal breakage in normal and dwarf mice

    NARCIS (Netherlands)

    Buul, P.P.W. van; Buul-Offers, S. van

    1982-01-01

    Treatment of dwarf mice with growth hormone, insulin and testosterone had no effect on the spontaneous frequencies of micronuclei (MN) in bone-marrow cells, whereas thyroxine decreased these frequencies. The induction of MN by X-rays and mitomycin C was significantly lower in dwarf mice than in norm

  12. The susceptibility to cytotoxic T lymphocyte mediated lysis of chemically induced sarcomas from immunodeficient and normal mice

    DEFF Research Database (Denmark)

    Svane, I M; Engel, A M; Thomsen, Allan Randrup

    1997-01-01

    tested for susceptibility to cytolysis by virus specific cytotoxic T cells. Tumour cells originating from tumours induced in immunocompetent C.B.-17 mice presented virus antigen more efficiently than tumour cells from immunodeficient SCID mice. No significant difference in virus antigen presentation...

  13. Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet.

    Science.gov (United States)

    Douris, Nicholas; Melman, Tamar; Pecherer, Jordan M; Pissios, Pavlos; Flier, Jeffrey S; Cantley, Lewis C; Locasale, Jason W; Maratos-Flier, Eleftheria

    2015-10-01

    Ingestion of very low-carbohydrate ketogenic diets (KD) is associated with weight loss, lowering of glucose and insulin levels and improved systemic insulin sensitivity. However, the beneficial effects of long-term feeding have been the subject of debate. We therefore studied the effects of lifelong consumption of this diet in mice. Complete metabolic analyses were performed after 8 and 80weeks on the diet. In addition we performed a serum metabolomic analysis and examined hepatic gene expression. Lifelong consumption of KD had no effect on morbidity or mortality (KD vs. Chow, 676 vs. 630days) despite hepatic steatosis and inflammation in KD mice. The KD fed mice lost weight initially as previously reported (Kennnedy et al., 2007) and remained lighter and had less fat mass; KD consuming mice had higher levels of energy expenditure, improved glucose homeostasis and higher circulating levels of β-hydroxybutyrate and triglycerides than chow-fed controls. Hepatic expression of the critical metabolic regulators including fibroblast growth factor 21 were also higher in KD-fed mice while expression levels of lipogenic enzymes such as stearoyl-CoA desaturase-1 was reduced. Metabolomic analysis revealed compensatory changes in amino acid metabolism, primarily involving down-regulation of catabolic processes, demonstrating that mice eating KD can shift amino acid metabolism to conserve amino acid levels. Long-term KD feeding caused profound and persistent metabolic changes, the majority of which are seen as health promoting, and had no adverse effects on survival in mice.

  14. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    Science.gov (United States)

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P yam dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models.

  15. Tankyrase 2 Poly(ADP-Ribose) Polymerase Domain-Deleted Mice Exhibit Growth Defects but Have Normal Telomere Length and Capping

    Energy Technology Data Exchange (ETDEWEB)

    Hsiao, Susan J [ORNL; Poitras, Marc [New York University School of Medicine; Cook, Brandoch [New York University School of Medicine; Liu, Yie [National Institute on Aging, Baltimore; Smith, Susan [New York University School of Medicine

    2006-03-01

    Regulation of telomere length maintenance and capping are a critical cell functions in both normal and tumor cells. Tankyrase 2 (Tnks2) is a poly(ADP-ribose) polymerase (PARP) that has been shown to modify itself and TRF1, a telomere-binding protein. We show here by overexpression studies that tankyrase 2, like its closely related homolog tankyrase 1, can function as a positive regulator of telomere length in human cells, dependent on its catalytic PARP activity. To study the role of Tnks2 in vivo, we generated mice with the Tnks2 PARP domain deleted. These mice are viable and fertile but display a growth retardation phenotype. Telomere analysis by quantitative fluorescence in situ hybridization (FISH), flow-FISH, and restriction fragment analysis showed no change in telomere length or telomere capping in these mice. To determine the requirement foTnks2 in long-term maintenance of telomeres, we generated embryonic stem cells with the Tnks2 PARP domain deleted and observed no change, even upon prolonged growth, in telomere length or telomere capping. Together these results suggest that Tnkjs2 has a role in normal growth and development but is not essential for telomere length maintenance or telomere capping in mice.

  16. Meta-chlorophenylpiperazine attenuates formalin-induced nociceptive responses through 5-HT1/2 receptors in both normal and diabetic mice.

    OpenAIRE

    Takeshita, N; Yamaguchi, I.

    1995-01-01

    1. This study was designed to investigate the effect of meta-chlorophenylpiperazine (m-CPP; a 5-hydroxytryptamine (5-HT) receptor agonist) on the formalin-induced nociceptive responses in normal, insulin-dependent streptozotocin (STZ) diabetic and non-insulin dependent genetically diabetic (db/db) mice. 2. A subcutaneous injection of diluted formalin (1% formaldehyde in 0.9% saline, 10 microliters) under the plantar surface of the left hindpaw induced biphasic nociceptive responses, the first...

  17. Treatment of Klebsiella pneumoniae septicemia in normal and leukopenic mice by liposome-encapsulated muramyl tripeptide phosphatidylethanolamide

    NARCIS (Netherlands)

    P.M. Melissen (Petronella Maria Bernadette); W. van Vianen (Wim); I.A.J.M. Bakker-Woudenberg (Irma)

    1994-01-01

    textabstractThe effect of free muramyl tripeptide phosphatidylethanolamide (MTPPE) and liposome-encapsulated MTPPE (LE-MTPPE) on Klebsiella pneumoniae septicemia resulting from intraperitoneal bacterial inoculation was investigated in mice. When administering a single p

  18. Chrysobalanus icaco L. Leaves Normalizes Insulin Sensitivity and Blood Glucose and Inhibits Weight Gain in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    White, Pollyanna A S; Araújo, Jessica M D; Cercato, Luana M; Souza, Lucas A; Barbosa, Ana Paula Oliveira; Quintans-Junior, Lucindo José; Machado, Ubiratan F; Camargo, Enilton A; Brito, Luciana C; Santos, Marcio Roberto V

    2016-02-01

    Chrysobalanus icaco L. is a medicinal plant present in the Brazilian coastline and known for its hypoglicemic and antioxidant properties. Here, we assessed the beneficial metabolic effects of the aqueous extract of C. icaco (AECI) leaves in diet-induced obese mice. Swiss mice were fed standard chow (SC used as controls) or high-fat diet (HFD) to induce obesity. After 10 weeks, mice on each diet were divided into two groups with one group used as control while the other group treated with AECI for 4 weeks resulting in four groups of mice: SC; SC treated with AECI (SC + AECI); HFD; and HFD treated with AECI (HFD + AECI). AECI was administered drinking water at about 200 mg/kg. AECI was able to normalize insulin (13,682 ± 1090 vs. 9828 ± 485 AU, P fat storage in liver (72.60 ± 3.83%, P fat intake. These findings reinforce the use of AECI in hyperglycemia and highlight the potential extract's effect in preventing weight gain and fat accumulation in liver of diet-induced obese mice.

  19. Inhibition of intestinal bile acid transporter Slc10a2 improves triglyceride metabolism and normalizes elevated plasma glucose levels in mice.

    Directory of Open Access Journals (Sweden)

    Thomas Lundåsen

    Full Text Available Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2 and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c. Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF 15 mRNA and normalized bile acid synthesis in Slc10a2-/- mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2-Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes.

  20. Restricted feeding-induced sleep, activity, and body temperature changes in normal and preproghrelin-deficient mice.

    Science.gov (United States)

    Szentirmai, Eva; Kapás, Levente; Sun, Yuxiang; Smith, Roy G; Krueger, James M

    2010-02-01

    Behavioral and physiological rhythms can be entrained by daily restricted feeding (RF), indicating the existence of a food-entrainable oscillator (FEO). One manifestation of the presence of FEO is anticipatory activity to regularly scheduled feeding. In the present study, we tested if intact ghrelin signaling is required for FEO function by studying food anticipatory activity (FAA) in preproghrelin knockout (KO) and wild-type (WT) mice. Sleep-wake activity, locomotor activity, body temperature, food intake, and body weight were measured for 12 days in mice on a RF paradigm with food available only for 4 h daily during the light phase. On RF days 1-3, increases in arousal occurred. This response was significantly attenuated in preproghrelin KO mice. There were progressive changes in sleep architecture and body temperature during the subsequent nine RF days. Sleep increased at night and decreased during the light periods while the total daily amount of sleep remained at baseline levels in both KO and WT mice. Body temperature fell during the dark but was elevated during and after feeding in the light. In the premeal hours, anticipatory increases in body temperature, locomotor activity, and wakefulness were present from RF day 6 in both groups. Results indicate that the preproghrelin gene is not required for the manifestation of FAA but suggest a role for ghrelinergic mechanisms in food deprivation-induced arousal in mice.

  1. Environmental enrichment and social interaction improve cognitive function and decrease reactive oxidative species in normal adult mice.

    Science.gov (United States)

    Doulames, Vanessa; Lee, Sangmook; Shea, Thomas B

    2014-05-01

    Environmental stimulation and increased social interactions stimulate cognitive performance, while decrease in these parameters can exacerbate cognitive decline as a function of illness, injury, or age. We examined the impact of environmental stimulation and social interactions on cognitive performance in healthy adult C57B1/6J mice. Mice were housed for 1 month individually or in groups of three (to prevent or allow social interaction) in either a standard environment (SE) or an enlarged cage containing nesting material and items classically utilized to stimulate exploration and activity ("enriched environment"; EE). Cognitive performance was tested by Y maze navigation and Novel Object Recognition (NOR; which compares the relative amount of time mice spent investigating a novel vs. a familiar object). Mice maintained for 1 month under isolated conditions in the SE statistically declined in performance versus baseline in the Y maze (p species (ROS/RNS) in brain. Environmental enrichment did not influence ROS/RNS. These findings indicate that environmental and social enrichment can positively influence cognitive performance in healthy adult mice, and support the notion that proactive approaches may delay age-related cognitive decline.

  2. Inhibitory effects of whisky congeners on melanogenesis in mouse B16 melanoma cells.

    Science.gov (United States)

    Ohguchi, Kenji; Koike, Minako; Suwa, Yoshihide; Koshimizu, Seiichi; Mizutani, Yuki; Nozawa, Yoshinori; Akao, Yukihiro

    2008-04-01

    We examined the effect of whisky congeners, substances other than ethanol in whisky, on melanogenesis in mouse B16 melanoma cells. Treatment with whisky congeners significantly blocked melanogenesis. Our results indicate that the inhibitory effects of whisky congeners on melanogenesis is due to direct inhibition of tyrosinase activity and to suppression of tyrosinase protein levels.

  3. Oral candidosis by Candida albicans in normal and xerostomic mice Candidose oral por Candida albicans em camundongos normais e xerostômicos

    Directory of Open Access Journals (Sweden)

    Marilda Aparecida Gonçalves Totti

    2004-09-01

    Full Text Available The aim of this study was to analyze the effect of sialoadenectomy on the development of oral candidosis after one or four inoculations of Candida albicans. Initially, a suspension containing 10(8 cells/ml of C. albicans ATCC 36801 was prepared. Seventy-eight sialoadenectomized mice and a similar amount of mice with normal salivary flow received a single inoculation of C. albicans suspension. Another group with a similar number of mice received 4 inoculations. The control group consisted of 6 sialoadenectomized mice and 6 mice with normal salivary flow that were not inoculated with C. albicans. Candidosis development was studied histologically in the tongue of the animals 1, 2, 3, 5, and 8 days after inoculation and at 15-day intervals up to 165 days. According to the results obtained, it could be concluded that sialoadenectomy and a higher frequency of yeast inoculation influenced the presence and extension of candidosis lesions.O objetivo deste estudo foi analisar o efeito da sialoadenectomia sobre o desenvolvimento da candidose oral após uma ou quatro inoculações de Candida albicans. Inicialmente, uma suspensão contendo 10(8 células/ml de C. albicans ATCC 36801 foi preparada. Setenta e oito camundongos sialoadenectomizados e mesma quantidade de camundongos com fluxo salivar normal receberam uma única inoculação de suspensão de C. albicans. Outro grupo, com o mesmo número de camundongos, recebeu 4 inoculações. O grupo controle consistiu de 6 camundongos sialoadenectomizados e 6 com fluxo salivar normal que não foram inoculados com C. albicans. O desenvolvimento de candidose foi estudado histologicamente na língua dos animais em períodos de 1, 2, 3, 5 e 8 dias após a inoculação e em intervalos de 15 dias até 165 dias. De acordo com os resultados obtidos, conclui-se que a sialoadenectomia e uma maior freqüência de inoculação influenciaram na presença e extensão das lesões de candidose.

  4. Influence of Ganoderma lucidum (Curt.: Fr.) P. Karst. on T-cell-mediated immunity in normal and immunosuppressed mice line CBA/Ca.

    Science.gov (United States)

    Nizhenkovska, Iryna V; Pidchenko, Vitalii T; Bychkova, Nina G; Bisko, Nina A; Rodnichenko, Angela Y; Kozyko, Natalya O

    2015-09-01

    The article presents the results of the investigation of the effect of biomass powder of the fungus Ganoderma lucidum on T-cell-mediated immunity in normal and immunosuppressed mice CBA/Ca. Delayed-type hypersensitivity assay was used. Experimental immunodeficiency was established with intraperitoneal injection of the immunosuppressant cyclophosphamide at a single dose of 150 mg/kg on the first day of the experiment. Results of the study show that the administration of biomass powder of Ganoderma lucidum in a dose of 0.5 mg/kg orally for 10 days increases the delayed-type hypersensitivity response in normal mice CBA/Ca. Administration of 0.5 mg/kg of biomass powder of the fungus Ganoderma lucidum for 10 days blocked the development of the T-cell-mediated immunosuppression, induced by administration of cyclophosphamide and restored the delayed-type hypersensitivity response in immunosuppressed mice. Key words: fungus Ganoderma lucidum cyclophosphamide immunodeficiency T-cell-mediated immunity delayed-type hypersensitivity.

  5. Mice deficient for striatal Vesicular Acetylcholine Transporter (VAChT) display impaired short-term but normal long-term object recognition memory.

    Science.gov (United States)

    Palmer, Daniel; Creighton, Samantha; Prado, Vania F; Prado, Marco A M; Choleris, Elena; Winters, Boyer D

    2016-09-15

    Substantial evidence implicates Acetylcholine (ACh) in the acquisition of object memories. While most research has focused on the role of the cholinergic basal forebrain and its cortical targets, there are additional cholinergic networks that may contribute to object recognition. The striatum contains an independent cholinergic network comprised of interneurons. In the current study, we investigated the role of this cholinergic signalling in object recognition using mice deficient for Vesicular Acetylcholine Transporter (VAChT) within interneurons of the striatum. We tested whether these striatal VAChT(D2-Cre-flox/flox) mice would display normal short-term (5 or 15min retention delay) and long-term (3h retention delay) object recognition memory. In a home cage object recognition task, male and female VAChT(D2-Cre-flox/flox) mice were impaired selectively with a 15min retention delay. When tested on an object location task, VAChT(D2-Cre-flox/flox) mice displayed intact spatial memory. Finally, when object recognition was tested in a Y-shaped apparatus, designed to minimize the influence of spatial and contextual cues, only females displayed impaired recognition with a 5min retention delay, but when males were challenged with a 15min retention delay, they were also impaired; neither males nor females were impaired with the 3h delay. The pattern of results suggests that striatal cholinergic transmission plays a role in the short-term memory for object features, but not spatial location.

  6. COMMUNICATION: Folate and S-adenosylmethionine modulate synaptic activity in cultured cortical neurons: acute differential impact on normal and apolipoprotein-deficient mice

    Science.gov (United States)

    Serra, Michael; Chan, Amy; Dubey, Maya; Gilman, Vladimir; Shea, Thomas B.

    2008-12-01

    Folate deficiency is accompanied by a decline in the cognitive neurotransmitter acetylcholine and a decline in cognitive performance in mice lacking apolipoprotein E (ApoE-/- mice), a low-density lipoprotein that regulates aspects of lipid metabolism. One direct consequence of folate deficiency is a decline in S-adenosylmethionine (SAM). Since dietary SAM supplementation maintains acetylcholine levels and cognitive performance in the absence of folate, we examined herein the impact of folate and SAM on neuronal synaptic activity. Embryonic cortical neurons from mice expressing or lacking ApoE (ApoE+/+ or -/-, respectively) were cultured for 1 month on multi-electrode arrays, and signaling was recorded. ApoE+/+ cultures displayed significantly more frequent spontaneous signals than ApoE-/- cultures. Supplementation with 166 µm SAM (not normally present in culture medium) increased signal frequency and decreased signal amplitude in ApoE+/+ cultures. SAM also increased the frequency of tightly clustered signal bursts. Folate deprivation reversibly reduced signal frequency in ApoE+/+ cultures; SAM supplementation maintained signal frequency despite folate deprivation. These findings support the importance of dietary supplementation with folate and SAM on neuronal health. Supplementation with 166 µm SAM did not alter signaling in ApoE-/- cultures, which may be a reflection of the reduced SAM levels in ApoE-/- mice. The differential impact of SAM on ApoE+/+ and -/- neurons underscores the combined impact of nutritional and genetic deficiencies on neuronal homeostasis.

  7. Intake of Wild Blueberry Powder Improves Episodic-Like and Working Memory during Normal Aging in Mice.

    Science.gov (United States)

    Beracochea, Daniel; Krazem, Ali; Henkouss, Nadia; Haccard, Guillaume; Roller, Marc; Fromentin, Emilie

    2016-08-01

    The number of Americans older than 65 years old is projected to more than double in the next 40 years. Cognitive changes associated to aging can affect an adult's day-to-day functioning. Among these cognitive changes, reasoning, episodic memory, working memory, and processing speed decline gradually over time. Early memory changes include a decline in both working and episodic memory. The aim of the present study was to determine whether chronic (up to 75 days) daily administration of wild blueberry extract or a wild blueberry full spectrum powder would help prevent memory failure associated with aging in tasks involving various forms of memory. Both blueberry ingredients were used in a study comparing young mice (6 months old) to aged mice (18 months old). At this age, mice exhibit memory decline due to aging, which is exacerbated first by a loss in working and contextual (episodic-like) memory. Contextual memory (episodic-like memory) was evaluated using the contextual serial discrimination test. Working and spatial memory were evaluated using the Morris-Water maze test and the sequential alternation test. Statistical analysis was performed using an ANOVA with the Bonferroni post-hoc test. Supplementation with wild blueberry full spectrum powder and wild blueberry extract resulted in significant improvement of contextual memory, while untreated aged mice experienced a decline in such memory. Only the wild blueberry full spectrum powder significantly contributed to an improvement of spatial and working memory versus untreated aged mice. These improvements of cognitive performance may be related to brain oxidative status, acetylcholinesterase activity, neuroprotection, or attenuation of immunoreactivity.

  8. Lack of effects of a "sobering" product, "Eezup!", on the blood ethanol and congener alcohol concentration.

    Science.gov (United States)

    Wunder, Cora; Hain, Sarah; Koelzer, Sarah C; Paulke, Alexander; Verhoff, Marcel A; Toennes, Stefan W

    2017-09-01

    The lifestyle product 'Eezup!' appeared on the German market and promised to normalize energy metabolism. Among vitamins (B1, B2, B6, C, E and zinc), rice protein and fructose the addition of alcohol dehydrogenase and catalase enzymes is a novel approach. The product was advertised as capable of boosting the rate of alcohol elimination. Seventeen subjects (11 men, 6 women, 19-58 years old), participated in a two-way crossover drinking study. Unfiltered wheat beer (4.4g% alcohol content) was drank within one hour to reach blood alcohol concentrations of 1‰ (1g/kg whole blood). On one day "Eezup!" was taken according to the manufacturer's instructions before and after drinking which was substituted for a placebo on the second test day. Blood samples were taken during 9h and ethanol and congener alcohols were determined. A comparison of Cmax, tmax, area under the curve (AUC) for ethanol and congener alcohols, and the hourly elimination rate of ethanol (β60) was performed to investigate an effect of Eezup!. Ethanol concentrations (Cmax) were in the range of 0,63-1,00‰ (median 0,85‰) and 0.62-1.22‰ (median 0.84‰) in the placebo and "Eezup!" condition, respectively, and not statistically different. Also tmax (1-2.5h) and AUCs did not differ. The ethanol elimination rates were 0.16‰/h (0.14-0.19‰/h) and 0.17‰/h (0.14-0.22 ‰/h) in the placebo and "Eezup!" condition without significant difference. The pharmacokinetic parameters of the congener alcohols (1-propanol, isobutanol, 3-methyl-1-butanol, 2-methyl-1-butanol) as well as of methanol did also not differ. The results of the present study failed to show any effect of the sobering product "Eezup!" on the amount of ethanol and congener alcohols absorbed (Cmax, tmax, AUC) and on the ethanol elimination rate (β60). Copyright © 2017 Elsevier B.V. All rights reserved.

  9. EFFECT OF TRIGONELLA FOENUM GRAECUM ON LACTATE DEHYDROGENASE (LDH ACTIVITY OF BLOOD, LIVER AND PANCREAS IN NORMAL AND ALLOXAN- INDUCED DIABETIC MICE

    Directory of Open Access Journals (Sweden)

    Sekaran Sridhar et al.

    2012-02-01

    Full Text Available The effect of aqueous seeds extract of Trigonella foenum graecum Linn was studied on Lactate dehydrogenase (LDH activity of blood, liver and pancreas in normal and alloxan- induced diabetic mice. Our study showed that aqueous seeds extract, Oral administration of 50 mg/animal (0.5 ml of extract in alternative days up to 7 days (1st, 3rd, 5th & 7th day. In alloxan induced diabetic mice, there was a significant increase in LDH activity of all the three tissues. The enzyme Lactate dehydrogenase showed significant decrease in the diabetic group treated with aqueous extract of tested plant when compared with the diabetic group. It is clear from the current data in this study that ginseng aqueous extract was the most efficient of the tested plant.

  10. Liver Steatosis and Increased ChREBP Expression in Mice Carrying a Liver Specific SIRT1 Null Mutation under a Normal Feeding Condition

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    Rui-Hong Wang, Cuiling Li, Chu-Xia Deng

    2010-01-01

    Full Text Available SIRT1, a homolog of yeast Sir2, is a type III NAD+ dependent histone and protein deacetylase. Previous studies of mice carrying liver specific deletion of exon 4 of the Sirt1 gene revealed opposite responses of mutant mice to a high-fat diet in terms of fatty liver formation, which obscures the function of SRIT1 in liver development and lipid metabolism. To investigate this, we deleted exons 5 and 6 of Sirt1 in the liver by using a Cre-loxP approach. Western blot using an antibody to N-terminal SIRT1 does not detect a truncated protein in the liver of the mutant mice (Sirt1flox5-6/flox5-6;Alb-Cre, suggesting a null mutation for SIRT1 is generated in the liver. Unlike the previously reported phenotypes, the Sirt1flox5-6/flox5-6;Alb-Cre mice develop fatty liver under a normal feeding condition. The disease starts at two months of age and incidence increases as the animals become older, affecting 78% of them when they are over one year of age. We showed that the steatosis is accompanied by altered expression of a number of genes, including increased expression of ChREBP, which acts as one of the central determinants of lipid synthesis in the liver. This data uncovers an important role of SIRT1 in regulating lipid metabolism in the liver, and the SIRT1 mutant mice may serve as an animal model for studying human fatty liver disease and facilitate the development of effective therapeutic approach for the disease.

  11. Automated Spatial Brain Normalization and Hindbrain White Matter Reference Tissue Give Improved [(18)F]-Florbetaben PET Quantitation in Alzheimer's Model Mice.

    Science.gov (United States)

    Overhoff, Felix; Brendel, Matthias; Jaworska, Anna; Korzhova, Viktoria; Delker, Andreas; Probst, Federico; Focke, Carola; Gildehaus, Franz-Josef; Carlsen, Janette; Baumann, Karlheinz; Haass, Christian; Bartenstein, Peter; Herms, Jochen; Rominger, Axel

    2016-01-01

    Preclinical PET studies of β-amyloid (Aβ) accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore, we aimed to evaluate systematically the (1) impact of an automated algorithm for spatial brain normalization, and (2) intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a 6 week longitudinal setting (N = 37) and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40) were investigated by [(18)F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ). For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX∕REF), relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen's d), and in reference to gold standard histopathological quantitation (Pearson's R). Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ≥0.99) between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX∕REF. All SUVRCTX∕REF methods performed better than SUVCTX both with regard to longitudinal stability (d≥1.21 vs. d = 0.23) and histological gold standard agreement (R≥0.66 vs. R≥0.31). Voxel-wise analysis suggested a physiologically implausible longitudinal decrease by global mean scaling. The hindbrain white matter reference (R mean = 0.75) was slightly superior to the brainstem (R mean = 0.74) and the cerebellum (R mean = 0.73). Automated

  12. Automated spatial brain normalization and hindbrain white matter reference tissue give improved [18F]-florbetaben PET quantitation in Alzheimer´s model mice

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    Felix eOverhoff

    2016-02-01

    Full Text Available Preclinical PET studies of β-amyloid (Aβ accumulation are of growing importance, but comparisons between research sites require standardized and optimized methods for quantitation. Therefore we aimed to evaluate systematically the 1 impact of an automated algorithm for spatial brain normalization, and 2 intensity scaling methods of different reference regions for Aβ-PET in a large dataset of transgenic mice. PS2APP mice in a six week longitudinal setting (N = 37 and another set of PS2APP mice at a histologically assessed narrow range of Aβ burden (N = 40 were investigated by [18F]-florbetaben PET. Manual spatial normalization by three readers at different training levels was performed prior to application of an automated brain spatial normalization and inter-reader agreement was assessed by Fleiss Kappa (κ. For this method the impact of templates at different pathology stages was investigated. Four different reference regions on brain uptake normalization were used to calculate frontal cortical standardized uptake value ratios (SUVRCTX/REF, relative to raw SUVCTX. Results were compared on the basis of longitudinal stability (Cohen’s d, and in reference to gold standard histopathological quantitation (Pearson’s R.Application of an automated brain spatial normalization resulted in nearly perfect agreement (all κ ≥ 0.99 between different readers, with constant or improved correlation with histology. Templates based on inappropriate pathology stage resulted in up to 2.9% systematic bias for SUVRCTX/REF. All SUVRCTX/REF methods performed better than SUVCTX both with regard to longitudinal stability (d ≥ 1.21 vs. d = 0.23 and histological gold standard agreement (R ≥ 0.66 vs. R ≥ 0.31. Voxel-wise analysis suggested a physiologically implausible longitudinal decrease of global mean scaling. The hindbrain white matter reference (Rmean = 0.75 was slightly superior to the brainstem (Rmean = 0.74 and the cerebellum (Rmean = 0

  13. Raman spectroscopy analysis of differences in composition of spent culture media of in vitro cultured preimplantation embryos isolated from normal and fat mice dams.

    Science.gov (United States)

    Fabian, Dušan; Kačmarová, Martina; Kubandová, Janka; Čikoš, Štefan; Koppel, Juraj

    2016-06-01

    The aim of the present study was to compare overall patterns of metabolic activity of in vitro cultured preimplantation embryos isolated from normal and fat mice dams by means of non-invasive profiling of spent culture media using Raman spectroscopy. To produce females with two different types of body condition (normal and fat), a previously established two-generation model was used, based on overfeeding of experimental mice during prenatal and early postnatal development. Embryos were isolated from spontaneously ovulating and naturally fertilized dams at the 2-cell stage of development and cultured to the blastocyst stage in synthetic oviductal medium KSOMaa. Embryos from fat mice (displaying significantly elevated body weight and fat) showed similar developmental capabilities in vitro as embryos isolated from normal control dams (displaying physiological body weight and fat). The results show that alterations in the composition of culture medium caused by the presence of developing mouse preimplantation embryos can be detected using Raman spectroscopy. Metabolic activity of embryos was reflected in evident changes in numerous band intensities in the 1620-1690cm(-1) (amide I) region and in the 1020-1140cm(-1) region of the Raman spectrum for KSOMaa. Moreover, multivariate analysis of spectral data proved that the composition of proteins and other organic compounds in spent samples obtained after the culture of embryos isolated from fat dams was different from that in spent samples obtained after the culture of embryos from control dams. This study demonstrates that metabolic activity of cultured preimplantation embryos might depend on the body condition of their donors.

  14. Chronic up-regulation of the SHH pathway normalizes some developmental effects of trisomy in Ts65Dn mice.

    Science.gov (United States)

    Dutka, Tara; Hallberg, Dorothy; Reeves, Roger H

    2015-02-01

    Down Syndrome (DS) is a highly complex developmental genetic disorder caused by trisomy for human chromosome 21 (Hsa21). All individuals with DS exhibit some degree of brain structural changes and cognitive impairment; mouse models such as Ts65Dn have been instrumental in understanding the underlying mechanisms. Several phenotypes of DS might arise from a reduced response of trisomic cells to the Sonic Hedgehog (SHH) growth factor. If all trisomic cells show a similar reduced response to SHH, then up-regulation of the pathway in trisomic cells might ameliorate multiple DS phenotypes. We crossed Ptch1tm1Mps/+ mice, in which the canonical SHH pathway is expected to be up-regulated in every SHH-responsive cell due to the loss of function of one allele of the pathway suppressor, Ptch1, to the Ts65Dn DS model and assessed the progeny for possible rescue of multiple DS-related phenotypes. Down-regulation of Ptch produced several previously unreported effects on development by itself, complicating interpretation of some phenotypes, and a number of structural or behavioral effects of trisomy were not compensated by SHH signaling. However, a deficit in a nest-building task was partially restored in Ts;Ptch+/- mice, as were the structural anomalies of the cerebellum seen in Ts65Dn mice. These results extend the body of evidence indicating that reduced response to SHH in trisomic cells and tissues contributes to various aspects of the trisomic phenotype.

  15. Cellular resilience: 5-HT neurons in Tph2(-/-) mice retain normal firing behavior despite the lack of brain 5-HT.

    Science.gov (United States)

    Montalbano, Alberto; Waider, Jonas; Barbieri, Mario; Baytas, Ozan; Lesch, Klaus-Peter; Corradetti, Renato; Mlinar, Boris

    2015-11-01

    Considerable evidence links dysfunction of serotonin (5-hydroxytryptamine, 5-HT) transmission to neurodevelopmental and psychiatric disorders characterized by compromised "social" cognition and emotion regulation. It is well established that the brain 5-HT system is under autoregulatory control by its principal transmitter 5-HT via its effects on activity and expression of 5-HT system-related proteins. To examine whether 5-HT itself also has a crucial role in the acquisition and maintenance of characteristic rhythmic firing of 5-HT neurons, we compared their intrinsic electrophysiological properties in mice lacking brain 5-HT, i.e. tryptophan hydroxylase-2 null mice (Tph2(-/-)) and their littermates, Tph2(+/-) and Tph2(+/+), by using whole-cell patch-clamp recordings in a brainstem slice preparation and single unit recording in anesthetized animals. We report that the active properties of dorsal raphe nucleus (DRN) 5-HT neurons in vivo (firing rate magnitude and variability; the presence of spike doublets) and in vitro (firing in response to depolarizing current pulses; action potential shape) as well as the resting membrane potential remained essentially unchanged across Tph2 genotypes. However, there were subtle differences in subthreshold properties, most notably, an approximately 25% higher input conductance in Tph2(-/-) mice compared with Tph2(+/-) and Tph2(+/+) littermates (presilience to complete brain 5-HT deficiency.

  16. Bioaccumulation of toxaphene congeners in the lake superior food web

    Science.gov (United States)

    Muir, D.C.G.; Whittle, D.M.; De Vault, D. S.; Bronte, C.R.; Karlsson, H.; Backus, S.; Teixeira, C.

    2004-01-01

    The bioaccumulation and biotransformation of toxaphene was examined in the food webs of Lake Superior and Siskiwit Lake (Isle Royale) using congener specific analysis as well as stable isotope ratios of carbon and nitrogen to characterize food webs. Toxaphene concentrations (calculated using technical toxaphene) in lake trout (Salvelinus namaycush) from the western basin of Lake Superior (N = 95) averaged (±SD) 889 ± 896 ng/g wet wt and 60 ± 34 ng/g wet wt in Siskiwit Lake. Major congeners in lake trout were B8-789 (P38), B8-2226 (P44), B9-1679 (P50), and B9-1025 (P62). Toxaphene concentrations were found to vary seasonally, especially in lower food web organisms in Lake Superior and to a lesser extent in Siskiwit Lake. Toxaphene concentrations declined significantly in lake herring (Coregonus artedii), rainbow smelt (Omerus mordax), and slimy sculpin (Cottus cognatus) as well as in zooplankton (> 102 &mn;m) and Mysis (Mysis relicta) between May and October. The seasonal variation may reflect seasonal shifts in the species abundance within the zooplankton community. Trophic magnification factors (TMF) derived from regressions of toxaphene congener concentrations versus δ15N were > 1 for most octa- and nonachlorobornanes in Lake Superior except B8-1413 (P26) and B9-715. Log bioaccumulation factors (BAFs) for toxaphene congeners in lake trout (ng/g lipid/ng/L dissolved) ranged from 4.54 to 9.7 and were significantly correlated with log octanol-water partition coefficients. TMFs observed for total toxaphene and congener B9-1679 in Lake Superior were similar to those in Arctic lakes, as well as to previous studies in the Great Lakes, which suggests that the bioaccumulation behavior of toxaphene is similar in pelagic food webs of large, cold water systems. However, toxaphene concentrations were lower in lake trout from Siskiwit Lake and lakes in northwestern Ontario than in Lake Superior possibly because of shorter food chains and greater reliance on zooplankton or

  17. Congener-specific metabolism and sequestration of dioxin-like compounds by cytochrome P450 1A induced in the liver of crows from Tokyo, Japan

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, M.; Iwata, H.; Tanabe, S. [Ehime Univ., Matsuyama (Japan); Yoneda, K.; Hashimoto, T. [Japan Wildlife Research Center, Tokyo (Japan)

    2004-09-15

    Jungle crow (JC; Corvus macrorhynchos) is a useful bioindicator for monitoring contaminants in urban areas, because this species is residential, occupies a same habitat as human, and feeds variety of foods including domestic waste and garbage. Therefore, JCs may accumulate environmental contaminants such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and coplanar polychlorinated biphenyls (Co-PCBs), which are released by human activities. Induction of cytochrome P450 (CYP) 1A is a responsive mechanism elicited by exposure to dioxinlike compounds including PCDDs/DFs and Co-PCBs. Toxicokinetic behavior of dioxin-like compounds in organisms is controlled by excretion, metabolism and absorption. These processes are, at least partly, dependent on CYP1A expression in addition to chemical structure and number of chlorine substitution of each congener. Low chlorinated congeners such as 2378-T{sub 4}CDD, 2378- T{sub 4}CDF, 12378-P{sub 5}CDD and 33'44'-PCB were easily metabolized by CYP1A1/2 in rat liver microsomes. PCDDs/DFs accumulate in hepatic tissue to a greater extent than adipose tissue in rats and mice. Recent study using transgenic CYP1A2 knockout mice demonstrated that CYP1A2 is responsible for the sequestration of 2378-T{sub 4}CDD and 23478-P{sub 5}CDF in hepatic tissue. Therefore, CYP1A is considered as a key factor responsible for toxicokinetics of dioxin-like compounds. However, there's no comprehensive data on the contribution of CYP1A to the toxicokinetics of dioxin-like congeners in wild populations. In this study, we investigated contamination levels of PCDDs/DFs and Co-PCBs in liver and breast muscle of JCs from Tokyo, Japan, and interactions of dioxin-like congeners with hepatic CYP to elucidate congener-specific toxicokinetics related to CYP expression in JC.

  18. Cyclodextrin has conflicting actions on autophagy flux in vivo in brains of normal and Alzheimer model mice.

    Science.gov (United States)

    Yang, Dun-Sheng; Stavrides, Philip; Kumar, Asok; Jiang, Ying; Mohan, Panaiyur S; Ohno, Masuo; Dobrenis, Kostantin; Davidson, Cristin D; Saito, Mitsuo; Pawlik, Monika; Huo, Chunfeng; Walkley, Steven U; Nixon, Ralph A

    2017-03-01

    2-hydroxypropyl-β-cyclodextrin (CYCLO), a modifier of cholesterol efflux from cellular membrane and endo-lysosomal compartments, reduces lysosomal lipid accumulations and has therapeutic effects in animal models of Niemann-Pick disease type C and several other neurodegenerative states. Here, we investigated CYCLO effects on autophagy in wild-type mice and TgCRND8 mice-an Alzheimer's Disease (AD) model exhibiting β-amyloidosis, neuronal autophagy deficits leading to protein and lipid accumulation within greatly enlarged autolysosomes. A 14-day intracerebroventricular administration of CYCLO to 8-month-old TgCRND8 mice that exhibit moderately advanced neuropathology markedly diminished the sizes of enlarged autolysosomes and lowered their content of GM2 ganglioside and Aβ-immunoreactivity without detectably altering amyloid precursor protein processing or extracellular Aβ/β-amyloid burden. We identified two major actions of CYCLO on autophagy underlying amelioration of lysosomal pathology. First, CYCLO stimulated lysosomal proteolytic activity by increasing cathepsin D activity, levels of cathepsins B and D and two proteins known to interact with cathepsin D, NPC1 and ABCA1. Second, CYCLO impeded autophagosome-lysosome fusion as evidenced by the accumulation of LC3, SQSTM1/p62, and ubiquitinated substrates in an expanded population of autophagosomes in the absence of greater autophagy induction. By slowing substrate delivery to lysosomes, autophagosome maturational delay, as further confirmed by our in vitro studies, may relieve lysosomal stress due to accumulated substrates. These findings provide in vivo evidence for lysosomal enhancing properties of CYCLO, but caution that prolonged interference with cellular membrane fusion/autophagosome maturation could have unfavorable consequences, which might require careful optimization of dosage and dosing schedules. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please

  19. Performance comparison of ultrasound-based methods to assess aortic diameter and stiffness in normal and aneurysmal mice.

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    Bram Trachet

    Full Text Available Several ultrasound-based methods are currently used to assess aortic diameter, circumferential strain and stiffness in mice, but none of them is flawless and a gold standard is lacking. We aimed to assess the validity and sensitivity of these methods in control animals and animals developing dissecting abdominal aortic aneurysm.We first compared systolic and diastolic diameters as well as local circumferential strains obtained in 47 Angiotensin II-infused ApoE(-/- mice with three different techniques (BMode, short axis MMode, long axis MMode, at two different abdominal aortic locations (supraceliac and paravisceral, and at three different time points of abdominal aneurysm formation (baseline, 14 days and 28 days. We found that short axis BMode was preferred to assess diameters, but should be avoided for strains. Short axis MMode gave good results for diameters but high standard deviations for strains. Long axis MMode should be avoided for diameters, and was comparable to short axis MMode for strains. We then compared pulse wave velocity measurements using global, ultrasound-based transit time or regional, pressure-based transit time in 10 control and 20 angiotensin II-infused, anti-TGF-Beta injected C57BL/6 mice. Both transit-time methods poorly correlated and were not able to detect a significant difference in PWV between controls and aneurysms. However, a combination of invasive pressure and MMode diameter, based on radio-frequency data, detected a highly significant difference in local aortic stiffness between controls and aneurysms, with low standard deviation.In small animal ultrasound the short axis view is preferred over the long axis view to measure aortic diameters, local methods are preferred over transit-time methods to measure aortic stiffness, invasive pressure-diameter data are preferred over non-invasive strains to measure local aortic stiffness, and the use of radiofrequency data improves the accuracy of diameter, strain as well

  20. Assessment of the toxic potential of PCB congener 81 (3,4,4[prime],5-tetrachlorobiphenyl) to fish in relation to other non-ortho-substituted PCB congeners

    Energy Technology Data Exchange (ETDEWEB)

    Harris, G.E.; Kiparissis, Y.; Metcalfe, C.D. (Trent Univ., Peterborough, Ontario (Canada). Environmental and Resource Studies Program)

    1994-09-01

    PCB congener 81 (3,4,4[prime],5-tetrachlorobiphenyl) has been detected in fish tissues from various sites in North America. The embryotoxicity of this compound to medaka (Oryzias latipes) and the induction of hepatic aryl hydrocarbon hydroxylase (AHH) in rainbow trout (Oncorhynchus mykiss) were determined to assess the toxic potency of this compound relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and two other non-ortho-substituted PCB compounds, congener 77 (3,3[prime],4,4[prime]-tetrachlorobiphenyl) and congener 126 (3,3[prime],4,4[prime],5-pentachlorobiphenyl). The TCDD toxic equivalency factors (TEFs) estimated for congener 81 from two end points in the medaka embryotoxicity assay were 0.0014 (from mortality data) and 0.006 (from swim bladder inflation data). The TEF estimated for congener 81 from data on AHH induction in rainbow trout was 0.004. All TEFs were greater than those estimated for congener 77 but were less than the TEFs estimated for congener 126. On the basis of these toxicity data, it is suggested that this congener may contribute significantly to the toxic burden of planar halogenated aromatic hydrocarbon in fish.

  1. Normal hematopoietic stem cell function in mice with enforced expression of the Hippo signaling effector YAP1.

    Directory of Open Access Journals (Sweden)

    Lina Jansson

    Full Text Available The Hippo pathway has recently been implicated in the regulation of organ size and stem cells in multiple tissues. The transcriptional cofactor yes-associated protein 1 (Yap1 is the most downstream effector of Hippo signaling and is functionally repressed by the upstream components of the pathway. Overexpression of YAP1 stimulates proliferation of stem and progenitor cells in many tissues, consistent with inhibition of Hippo signaling. To study the role of Hippo signaling in hematopoietic stem cells (HSCs, we created a transgenic model with inducible YAP1 expression exclusively within the hematopoietic system. Following 3 months induction, examination of blood and bone marrow in the induced mice revealed no changes in the distribution of the hematopoietic lineages compared to control mice. Moreover, the progenitor cell compartment was unaltered as determined by colony forming assays and immunophenotyping. To address whether YAP1 affects the quantity and function of HSCs we performed competitive transplantation experiments. We show that ectopic YAP1 expression does not influence HSC function neither during steady state nor in situations of hematopoietic stress. This is in sharp contrast to effects seen on stem- and progenitor cells in other organs and suggests highly tissue specific functions of the Hippo pathway in regulation of stem cells.

  2. Deletion of JAM-C, a candidate gene for heart defects in Jacobsen syndrome, results in a normal cardiac phenotype in mice.

    Science.gov (United States)

    Ye, Maoqing; Hamzeh, Rabih; Geddis, Amy; Varki, Nissi; Perryman, M Benjamin; Grossfeld, Paul

    2009-07-01

    The 11q terminal deletion disorder (11q-) is a rare chromosomal disorder caused by a deletion in distal 11q. Fifty-six percent of patients have clinically significant congenital heart defects. A cardiac "critical region" has been identified in distal 11q that contains over 40 annotated genes. In this study, we identify the distal breakpoint of a patient with a paracentric inversion in distal 11q who had hypoplastic left heart and congenital thrombocytopenia. The distal breakpoint mapped to JAM-3, a gene previously identified as a candidate gene for causing HLHS in 11q-. To determine the role of JAM-3 in cardiac development, we performed a comprehensive cardiac phenotypic assessment in which the mouse homolog for JAM-3, JAM-C, has been deleted. These mice have normal cardiac structure and function, indicating that haplo-insufficiency of JAM-3 is unlikely to cause the congenital heart defects that occur in 11q- patients. Notably, we identified a previously undescribed phenotype, jitteriness, in most of the sick or dying adult JAM-C knockout mice. These data provide further insights into the identification of the putative disease-causing cardiac gene(s) in distal 11q, as well as the functions of JAM-C in normal organ development.

  3. Effect of radiation on normal hematopoiesis and on viral induced cancers of the hematopoietic system. Technical progress report, August 1, 1974--May 1, 1975. [Mice, x radiation

    Energy Technology Data Exchange (ETDEWEB)

    Okunewick, J.P.

    1975-01-01

    Studies carried out during the above period on viral leukemia have conclusively shown that the pluripotent hematopoietic colony forming stem cell (CFU-S) is a target cell for the leukemia virus. Treatment of this cell population with antiserum prepared in syngeneic mice against the disease resulted in inactivation of up to 50 percent of the CFU-S obtained from the spleens of viral leukemic mice. At the same time, normal serum had no effect on these cells, nor did the antiserum have any effect on normal CFU-S. Data indicated that a considerable time delay, on the order of a week, preceded the expression of the viral antigen in the leukemic CFU-S, but that it could be seen at all times after that up to the terminal point of the disease. We examined the effect of the virus on DNA synthesis (S-phase cells) in the CFU-S immediately after virus injection. The results showed that a doubling of the number of cells in S could be seen as early as four hours after introduction of the virus into the animal. Studies with ethidium bromide, an inhibitor of viral reverse transcriptase, were found to be in agreement with this observation. When given to viral leukemic animals in combination with fractionated exposure to x-ray, the data suggested that ethidium bromide did act to extend survival somewhat, but not much over that seen through the use of x-ray alone.

  4. Congener-specific accumulation and trophic transfer of polychlorinated biphenyls in spider crab food webs revealed by stable isotope analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, N. [IFREMER, DCN-BE, Technopole Brest-Iroise, Pointe du Diable, 29280 Plouzane (France); LPTC-UMR 5472 CNRS, Universite de Bordeaux 1, 351 cours de la Liberation, 33400 Talence (France)], E-mail: bodin.nathalie@caramail.com; Le Loc' h, F. [IRD, UR 070 RAP, Centre de Recherche Halieutique, Avenue Jean Monnet, B.P. 171, 34203 Sete Cedex (France); Caisey, X.; Le Guellec, A.-M.; Abarnou, A.; Loizeau, V. [IFREMER, DCN-BE, Technopole Brest-Iroise, Pointe du Diable, 29280 Plouzane (France); Latrouite, D. [IFREMER, DCB-STH, Technopole Brest-Iroise, Pointe du Diable, 29280 Plouzane (France)

    2008-01-15

    Polychlorobiphenyls (PCB) and stable isotopes ({delta}{sup 15}N and {delta}{sup 13}C) were analyzed in the spider crab (Maja brachydactyla) food web from the Iroise Sea (Western Brittany) and the Seine Bay (Eastern English Channel). PCB concentrations were all significantly higher in organisms from the Seine Bay than those from the Iroise Sea. PCB patterns were strongly related to the feeding mode of the species, and increased influence of higher chlorinated congeners was highlighted with trophic position of the organisms. PCB concentrations (lipid normalized) were significantly related to the isotopically derived trophic level (TL) in spider crab food webs. The highest trophic magnification factors (TMFs) were calculated for the congeners with 2,4,5-substitution, and were lower in the Seine Bay compared to the Iroise Sea. The confrontation of PCB and TL data also revealed biotransformation capacity of decapod crustaceans for specific congeners based on structure-activity relations. - The influence of feeding mode and trophic position on the fate of PCBs in spider crab food webs is discussed by using a stable isotopic approach.

  5. Effects of oral exposure to naturally-occurring and synthetic deoxynivalenol congeners on proinflammatory cytokine and chemokine mRNA expression in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Wenda [College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095 (China); Dept. of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); He, Kaiyu [Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Dept. of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States); Zhou, Hui-Ren [Dept. of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Berthiller, Franz [Christian Doppler Laboratory for Mycotoxin Metabolism and Center for Analytical Chemistry, University of Natural Resources and Life Sciences, Tulln (Austria); Adam, Gerhard [Dept. of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna (Austria); Sugita-Konishi, Yoshiko [Food and Life Sciences, Azabu University, 1-17-71 Fuchinobe Chuo-ku, Sagamihara, Kanagawa Pref., 252-5201 (Japan); Watanabe, Maiko [Division of Microbiology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501 (Japan); Krantis, Anthony [Dept. of Cellular and Molecular Medicine, University of Ottawa (Canada); Durst, Tony [Dept. of Chemistry, University of Ottawa (Canada); Zhang, Haibin [College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095 (China); Pestka, James J., E-mail: pestka@msu.edu [Dept. of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Center for Integrative Toxicology, Michigan State University, East Lansing, MI 48824 (United States); Dept. of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States)

    2014-07-15

    The foodborne mycotoxin deoxynivalenol (DON) induces a ribotoxic stress response in mononuclear phagocytes that mediate aberrant multi-organ upregulation of TNF-α, interleukins and chemokines in experimental animals. While other DON congeners also exist as food contaminants or pharmacologically-active derivatives, it is not known how these compounds affect expression of these cytokine genes in vivo. To address this gap, we compared in mice the acute effects of oral DON exposure to that of seven relevant congeners on splenic expression of representative cytokine mRNAs after 2 and 6 h. Congeners included the 8-ketotrichothecenes 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), fusarenon X (FX), nivalenol (NIV), the plant metabolite DON-3-glucoside (D3G) and two synthetic DON derivatives with novel satiety-inducing properties (EN139528 and EN139544). DON markedly induced transient upregulation of TNF-α IL-1β, IL-6, CXCL-2, CCL-2 and CCL-7 mRNA expressions. The two ADONs also evoked mRNA expression of these genes but to a relatively lesser extent. FX induced more persistent responses than the other DON congeners and, compared to DON, was: 1) more potent in inducing IL-1β mRNA, 2) approximately equipotent in the induction of TNF-α and CCL-2 mRNAs, and 3) less potent at upregulating IL-6, CXCL-2, and CCL-2 mRNAs. EN139528's effects were similar to NIV, the least potent 8-ketotrichothecene, while D3G and EN139544 were largely incapable of eliciting cytokine or chemokine mRNA responses. Taken together, the results presented herein provide important new insights into the potential of naturally-occurring and synthetic DON congeners to elicit aberrant mRNA upregulation of cytokines associated with acute and chronic trichothecene toxicity. - Highlights: • We compared effects of DON congeners on biomarker proinflammatory genes in mice. • Oral DON induced splenic IL-1β, IL-6, TNF-α,CXCL-2, CCL-2 and CCL-7 mRNAs. • 8-Ketotrichothecene ranking

  6. Nasal bone shape is under complex epistatic genetic control in mouse interspecific recombinant congenic strains.

    Directory of Open Access Journals (Sweden)

    Gaétan Burgio

    Full Text Available BACKGROUND: Genetic determinism of cranial morphology in the mouse is still largely unknown, despite the localization of putative QTLs and the identification of genes associated with Mendelian skull malformations. To approach the dissection of this multigenic control, we have used a set of interspecific recombinant congenic strains (IRCS produced between C57BL/6 and mice of the distant species Mus spretus (SEG/Pas. Each strain has inherited 1.3% of its genome from SEG/Pas under the form of few, small-sized, chromosomal segments. RESULTS: The shape of the nasal bone was studied using outline analysis combined with Fourier descriptors, and differential features were identified between IRCS BcG-66H and C57BL/6. An F2 cross between BcG-66H and C57BL/6 revealed that, out of the three SEG/Pas-derived chromosomal regions present in BcG-66H, two were involved. Segments on chromosomes 1 (∼32 Mb and 18 (∼13 Mb showed additive effect on nasal bone shape. The three chromosomal regions present in BcG-66H were isolated in congenic strains to study their individual effect. Epistatic interactions were assessed in bicongenic strains. CONCLUSIONS: Our results show that, besides a strong individual effect, the QTL on chromosome 1 interacts with genes on chromosomes 13 and 18. This study demonstrates that nasal bone shape is under complex genetic control but can be efficiently dissected in the mouse using appropriate genetic tools and shape descriptors.

  7. CD25+CD127+Foxp3- Cells Represent a Major Subpopulation of CD8+ T Cells in the Eye Chambers of Normal Mice

    Science.gov (United States)

    Ziółkowska, Natalia; Ziółkowski, Hubert; Małaczewska, Joanna

    2017-01-01

    The aim of this study has been to determine whether eye chambers constitute part of the normal migratory pathway of naive CD4+ and CD8+ T cells in mouse and if natural CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+ regulatory T cells are present within these eye compartments. To this aim, the cells obtained from aqueous humor (AH) of normal mice were phenotyped in terms of the expression CD4, CD8, CD25, CD127 and transcription factor Foxp3. The mean percentage of CD8+ T cells in the total AH lymphocyte population was as high as 28.69%; the mean percentage of CD8high and CD8low cells in this population was 34.09% and 65.91%, respectively. The presence of cells with the regulatory phenotype, i.e. CD25+Foxp3+ cells, constituted only 0.32% of CD8+ T cell subset. Regarding the expression of CD25, AH CD8+ T cells were an exceptional population in that nearly 85% of these cells expressed this molecule without concomitant Foxp3 expression. Despite having this phenotype, they should not be viewed as activated cells because most of them co-expressed CD127, which indicates that they are naive lymphocytes. With regard to the markers applied in the present research, CD8+CD25+CD127+Foxp3- T cells represent the most numerous subset of AH CD8+ cells. The results suggest that eye chambers in mice are an element in the normal migratory pathway of naive CD8+ T cells. The study presented herein demonstrated only trace presence of CD4+ cells in the eye chambers, as the mean percentage of these cells was just 0.56. Such selective and specific homing of CD8+ and CD4+ cells to the eye chambers is most clearly engaged in the induction and maintenance of ocular immune privilege. PMID:28081241

  8. Incubation stage and polychlorinated biphenyl (PCB) congener patterns in an altricial and precocial bird species.

    Science.gov (United States)

    Custer, Christine M; Custer, Thomas W; Thyen, Stefan; Becker, Peter H

    2014-12-01

    The composition of polychlorinated biphenyl (PCB) congeners was compared between non-incubated and embryonated eggs of tree swallows (Tachycineta bicolor) and little terns (Sterna albifrons) to determine if measurable changes in PCB congeners occurred during the embryonic period. There was no indication of changes in PCB congener patterns over the incubation period in tree swallows in 1999 and 2000 at a site with very high PCB exposure or a site with more modest PCB exposure. Additionally, congeners known to be either quickly metabolized or conserved based on experimental studies did not generally respond as predicted. Similarly, PCB congener patterns in eggs of little terns from Bottsand, Schleswig-Holstein, Germany, did not differ between non-incubated and embryonated eggs. The results from both species suggest that the stage of incubation is not an important consideration when evaluating PCB congener patterns; comparisons and assessments can be made with eggs collected at all stages of incubation.

  9. The Optimal Price Policy of Congener Software Product

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    From the viewpoint of market behavior to a certain softwaredevelopment company, it's very important to decide the suitable price to deploy its product. Especially face to the opponents who sale the congener product in the current market. According to the requirement of market economy and software engineering , accurate estimation of software price and its amount of sales are useful to a certain software provider to build a proper development project and software pro ducts' target parameters. Here we analysis the factors which affect the price of the congener software product in the same market, and calculate the weight of t hese factors to it's price on the current market. With the help of principles of the non-cooperative games, we built a model base on AHP methods. Use this model , we can get the optimal price to release our software product and the biggest turnover. At the end of this paper, we use a numerical example to explain how to use our model

  10. Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation.

    Science.gov (United States)

    Tong, Leslie M; Djukic, Biljana; Arnold, Christine; Gillespie, Anna K; Yoon, Seo Yeon; Wang, Max M; Zhang, Olivia; Knoferle, Johanna; Rubenstein, John L R; Alvarez-Buylla, Arturo; Huang, Yadong

    2014-07-16

    Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases.

  11. Congener-specific bioaccumulation of PCBs in different water bird species

    OpenAIRE

    Zimmermann, Gaby; Dietrich, Daniel R.; Schmid, Peter; Schlatter, Christian

    1997-01-01

    The bioaccumulation behaviour of single PCB congeners in three trophic levels of a food chain in an aquatic ecosystem was studied. Congener-specific biotransfer factors were calculated comparing PCB concentrations in tissues of 4 water bird species with the contents measured in their food source. The coplanar PCBs were of particular interest.The maximum concentrations of individual PCB congeners detected in mussels, fish and birds were 0.5, 4, and 26 μg/g extractable lipids, respectively. In ...

  12. Normal autophagic activity in macrophages from mice lacking Gαi3, AGS3, or RGS19.

    Directory of Open Access Journals (Sweden)

    Ali Vural

    Full Text Available In macrophages autophagy assists antigen presentation, affects cytokine release, and promotes intracellular pathogen elimination. In some cells autophagy is modulated by a signaling pathway that employs Gαi3, Activator of G-protein Signaling-3 (AGS3/GPSM1, and Regulator of G-protein Signaling 19 (RGS19. As macrophages express each of these proteins, we tested their importance in regulating macrophage autophagy. We assessed LC3 processing and the formation of LC3 puncta in bone marrow derived macrophages prepared from wild type, Gnai3(-/-, Gpsm1(-/-, or Rgs19(-/- mice following amino acid starvation or Nigericin treatment. In addition, we evaluated rapamycin-induced autophagic proteolysis rates by long-lived protein degradation assays and anti-autophagic action after rapamycin induction in wild type, Gnai3(-/-, and Gpsm1(-/- macrophages. In similar assays we compared macrophages treated or not with pertussis toxin, an inhibitor of GPCR (G-protein couple receptor triggered Gαi nucleotide exchange. Despite previous findings, the level of basal autophagy, autophagic induction, autophagic flux, autophagic degradation and the anti-autophagic action in macrophages that lacked Gαi3, AGS3, or RGS19; or had been treated with pertussis toxin, were similar to controls. These results indicate that while Gαi signaling may impact autophagy in some cell types it does not in macrophages.

  13. Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome

    Science.gov (United States)

    Serra, Montserrat; Matabosch, Xavier; Ying, Lee; Watson, Gordon; Shackleton, Cedric

    2010-01-01

    Our recent studies have focused on cholesterol synthesis in mouse models for 7-dehydrosterolreductase (DHCR7) deficiency, also known as Smith-Lemli-Opitz syndrome. Investigations of such mutants have relied on tissue and blood levels of the cholesterol precursor 7-dehydrocholesterol (7DHC) and its 8-dehydro isomer. In this investigation by gas chromatography/mass spectrometry (GC/MS) we have identified and quantified cholesterol and its precursors (7DHC, desmosterol, lathosterol, lanosterol and cholest-7,24-dien-3β-ol) in mouse hair. The components were characterized and their concentrations were compared to those found in mouse skin and serum. Hair appeared unique in that desmosterol was a major sterol component, almost matching in concentration cholesterol itself. In DHCR7 deficient mice, dehydrodesmosterol (DHD) was the dominant hair Δ7 sterol. Mutant mouse hair had much higher concentrations of 7-dehydrosterols relative to cholesterol than did serum or tissue at all ages studied. The 7DHC/C ratio in hair was typically about sevenfold the value in serum or skin and the DHD/D ratio was 100X that of the serum 7DHC/C ratio. Mutant mice compensate for their DHCR7 deficiency with maturity, and the tissue and blood 7DHC/C become close to normal. That hair retains high relative concentrations of the dehydro precursors suggests that the apparent up-regulation of Dhcr7 seen in liver is slower to develop at the site of hair cholesterol synthesis. PMID:20804844

  14. Fisetin-Rich Extracts of Rhus verniciflua Stokes Improve Blood Flow Rates in Mice Fed Both Normal and High-Fat Diets.

    Science.gov (United States)

    Im, Won Kyun; Park, Hyun Jung; Lee, Kwang Soo; Lee, Jung Hoon; Kim, Young Dong; Kim, Kyeong-Hee; Park, Sang-Jae; Hong, Seokmann; Jeon, Sung Ho

    2016-02-01

    Although it has been previously reported that Rhus verniciflua Stokes (RVS) possesses in vitro anti-inflammatory activity, the precise in vivo mechanisms of RVS extracts and a main active component called fisetin have not been well elucidated. In this study, using newly developed protocols, we prepared urushiol-free but fisetin-enriched RVS extracts and investigated their effects on the vascular immune system. We found that the water-soluble fractions of detoxified RVS with the flavonoid fisetin can inhibit lipopolysaccharide-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). Furthermore, RVS can reduce inducible nitric oxide synthase and COX2 gene expression levels, which are responsible for NO and PGE2 production, respectively, in RAW264.7 macrophage cells. Because inflammation is linked to the activation of the coagulation system, we hypothesized that RVS and its active component fisetin possess anticoagulatory activities. As expected, we found that both RVS and fisetin could inhibit the coagulation of human peripheral blood cells. Moreover, in vivo RVS treatment could return the retarded blood flow elicited by a high-fat diet (HFD) back to the normal level in mice. In addition, RVS treatment has significantly reduced body weight gained by HFD in mice. Taken together, the fisetin-rich RVS extracts have potential antiplatelet and antiobesity activities and could be used as a functional food ingredient to improve blood circulation.

  15. Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice.

    Science.gov (United States)

    Detrait, Eric R; Carr, Greg V; Weinberger, Daniel R; Lamberty, Yves

    2016-08-01

    The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brain-penetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders.

  16. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

    Science.gov (United States)

    Busby, Ellen R.; Sherwood, Nancy M.

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15–28 may account for the altered metabolism in the prepubertal female pups. PMID:28346489

  17. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice.

    Science.gov (United States)

    Busby, Ellen R; Sherwood, Nancy M

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15-28 may account for the altered metabolism in the prepubertal female pups.

  18. Hormonal regulation of intracellular lipolysis in C57BL/6J mice: effect of diet-induced adiposity and data normalization.

    Science.gov (United States)

    Bederman, Ilya R; Previs, Stephen F

    2008-10-01

    The breakdown of intracellular triglycerides in adipose tissue provides fatty acids and glycerol as substrates for oxidation. However, the exposure of target organs to excess free fatty acids is associated with the development of insulin resistance and impaired regulation of carbohydrate metabolism, suggesting that the control of triglyceride breakdown is an important factor in balancing health and disease. We have studied the temporal influence of diet-induced changes in adiposity on the response of intracellular lipolysis to epinephrine +/- insulin using freshly isolated adipocytes from C57BL/6J mice fed a low-fat (10% kcal) or high-fat (HF, 45% kcal) diet for 1, 4, or 12 weeks. In this model, we also tested how data normalization affects the interpretation. The contribution of the epididymal fat to total body mass increased by approximately 15%, 45%, and 100% after 1, 4, and 12 weeks of HF diet consumption, respectively. In addition, HF feeding led to an increase in fasting insulin, that is, approximately 2-fold greater in HF- vs low-fat-fed mice at 4 and 12 weeks. We found that diet-induced changes in adiposity did not alter the lipolytic response to epinephrine when data were normalized per DNA (ie, per cell); however, the lipolytic potential of the organ (ie, the lipolytic rate per cell multiplied by the total number of cells) was increased in isolated adipocytes after 4 and 12 weeks of HF feeding. We also observed a marked impairment in insulin-mediated inhibition of epinephrine-stimulated lipolysis after 4 and 12 weeks of HF feeding, demonstrating that diet-induced adiposity leads to insulin resistance in adipocytes. In conclusion, HF feeding in mice leads to greater rates of lipolysis via (1) an increase in the number of fat cells and (2) a defect in insulin signaling in adipocytes. The combination of these 2 alterations on the control of intracellular lipolysis suggests a mechanism(s) that (partly) explains how target organs could be exposed to excess

  19. Comparative study of two different Bombesin derivates labeled with {sup 111}In and biodistribution in normal mice

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Ricardo S.; Alcarde, Lais F.; Correa, Beatriz L.; Massicano, Adriana V.F.; Couto, Renata M.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: ricardooliveira@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Nuclear medicine is a medical speciality that uses radioactive compounds (radiopharmaceuticals), consisting of a substrate and a radioactive isotope, for diagnostic. Among the peptides of interest for Nuclear Medicine, bombesin (BBN), a 14 amino acid neuropeptide analog of human gastrin-releasing peptide, is one of the highlights. This is a comparative study aiming to establish the best condition to radiolabel two BBN derivatives, (DTPA-Phe-Gly{sub 5}-BBN{sub (6-14)}) and (DTPA-Phe-Gly{sub 2}-BBN{sub (6-14})) with 111-indium. Specific objectives of this study were evaluate a good condition of radiolabelling in search excellent specific activity the bombesin derivatives and determinate the biodistribution in health mice model. Ten micrograms (10μg) of the derivative DTPA-Phe-Gly2-BBN (6-14) was labeled with 18.5 MBq (0.5 mCi) of {sup 111}InCl{sub 3} at 25°C for different times (5, 15 and 30 minutes). The best condition was applied to peptide mass variation (10, 5, 2.5, 1, 0.5, 0.25 and 0.1 μg), keeping all other parameters fixed. Finally, the influence of {sup 111}InCl{sub 3} activity in the radiolabeling process (18.5, 37, 55.5, 74, 185 MBq) was evaluated. The best conditions were repeated for the second derivate, DTPA-Phe-Gly{sub 5}-BBN{sub (6-14}). The radiochemical purity was assessed by thin layer chromatography (TLC), using 0.2 M EDTA pH 5 as solvent, and high performance liquid chromatography (HPLC) with a C18 column with linear gradient 10% A to 90% A (v/v) (A: 0,1% of TFA in CH3CN; B: 0,1% of TFA in H2O) at a flow rate of 1 mL/minute for 15 minutes. Considering the reaction time, the higher radiochemical purity was obtained when 10μg of the peptide was labeled with 18.5 MBq (0.5 mCi) of {sup 111}In for 15 minutes at 25°C (97.33 ± 0.50%, n=3). In the mass variation study, the best results of radiochemical purity were obtained when 10 μg of the peptide was employed (97.69 ± 0.4%, n = 4). Finally, the maximum specific activity of the radiolabelled

  20. Bio- and chemical syntheses of mangiferin and congeners.

    Science.gov (United States)

    Ehianeta, Teddy Stephen; Laval, Stéphane; Yu, Biao

    2016-09-10

    Mangiferin (2C-β-d-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a xanthone C-glycoside occurring in many plant species. Composed of a glucose unit C1→2 linked to a 1,3,6,7-tetrahydroxyxanthone aglycone, mangiferin exhibits a wide range of biological activities, which recently renewed its interest as a potential pharmacophore. Mangiferin is mainly isolated after extraction procedures from natural sources alongside with its isoforms isomangiferin, homomangiferin, and neomangiferin. However, enzymatic and chemical approaches have been developed to access these phytochemicals, which address the challenging construction of the C-glycosidic linkage. In addition, both approaches have been exploited to modify the aglycone and the sugar moiety in order to afford analogues with specific and improved pharmacological activities. Herein, we provide a comprehensive review on the biosynthesis and chemical synthesis of mangiferin and its congeners. © 2016 BioFactors, 42(5):445-458, 2016.

  1. Neuroanatomical localization and quantification of amyloid precursor protein mRNA by in situ hybridization in the brains of normal, aneuploid, and lesioned mice

    Energy Technology Data Exchange (ETDEWEB)

    Bendotti, C.; Forloni, G.L.; Morgan, R.A.; O' Hara, B.F.; Oster-Granite, M.L.; Reeves, R.H.; Gearhart, J.D.; Coyle, J.T. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1988-05-01

    Amyloid precursor protein mRNA was localized in frozen sections from normal and experimentally lesioned adult mouse brain and from normal and aneuploid fetal mouse brain by in situ hybridization with a {sup 35}S-labeled mouse cDNA probe. The highest levels of hybridization in adult brain were associated with neurons, primarily in telencephalic structures. The dense labeling associated with hippocampal pyramidal cells was reduced significantly when the cells were eliminated by injection of the neurotoxin ibotenic acid but was not affected when electrolytic lesions were placed in the medial septum. Since the gene encoding amyloid precursor protein has been localized to mouse chromosome 16, the authors also examined the expression of this gene in the brains of mouse embryos with trisomy 16 and trisomy 19 at 15 days of gestation. RNA gel blot analysis and in situ hybridization showed a marked increase in amyloid precursor protein mRNA in the trisomy 16 mouse head and brain when compared with euploid littermates or with trisomy 19 mice.

  2. A Comparative Study on the Effect of BCG-PSN and Thymopeptides on T-lymphocyte Subsets of Normal and Immunosuppressed Mice

    Institute of Scientific and Technical Information of China (English)

    邓云华; 陈映玲; 陈兴平; 李永喜; 周礼义

    2003-01-01

    To compare the effects of polysaccharide nucleic acid fraction of bacillus calmette guerin (BCG-PSN) and thymopeptides on T-lymphocytes of normal and immunosuppressed mice, CD4+ and CD8+ T-lymphocyte subsets of single nucleic cell in thymus, spleen and peripheral blood were detected successively by flow cytometry after application of BCG-PSN and thymopeptides. Meanwhile, CD4+/CD8+ ratio was also calculated. The results showed that both BCG-PSN and thymopeptides could decrease the proportion of CD4+ CD8+ T-lymphocyte subsets in the thymus, at the same time increase CD4+ T-lymphocyte, CD8+ T-lymphocyte proportion in the three tissues.The fluctuation in amplitude was greater in thymopeptides group than that in BCG-PSN group. It is concluded that acting location of thymopeptides is in thymus, its stimulating action is stronger than that of BCG-PSN, while BCG-PSN not only accelerates the differentiation in thymus, but also has some direct stimulation to peripheral CD4+ T-lymphocytes, and can maintain CD4+/CD8+ ratio within normal range. So, BCG-PSN is safer.

  3. Polybrominated diphenyl ether congener (BDE-100) induces mitochondrial impairment.

    Science.gov (United States)

    Pereira, Lílian Cristina; de Souza, Alecsandra Oliveira; Dorta, Daniel Junqueira

    2013-06-01

    Brominated flame retardants are used in various consumer products to increase their resistance to fire and/or high temperatures. Polybrominated diphenyl ethers (PBDEs) are representatives of this class and among the most widely used congeners, and BDE-100 is produced on a large scale. There is a lack of toxicological data about these compounds, which has recently become a matter of concern to the scientific community. The mitochondria are recognized as the main energy-producing organelles, as well as playing a vital role in the maintenance of many cell functions. Therefore, mitochondria were used in the present work as an experimental model to evaluate the effects of the BDE-100 congeners at concentrations ranging from 0.1 μM to 50 μM. The results showed that high concentrations of BDE-100 were able to induce mitochondrial alterations. It was observed that the substance had an affinity for the hydrophilic portion of the mitochondrial membrane, as monitored by ANS, inhibiting the glutamate + malate-stimulated mitochondrial respiration and also inducing dissipation of the mitochondrial membrane potential, deregulation of calcium homoeostasis and mitochondrial swelling, the latter being insensitive to cyclosporin A (CsA) but partially inhibited by Ruthenium Red and N-ethyl maleimide. In addition, a significant reduction in mitochondrial ATP content was found, but on the other hand, no oxidative stress was observed after exposure of the mitochondria to BDE-100. These results show the key role of mitochondria in the cytotoxicity induced by BDE-100.

  4. Comparative developmental toxicity of planar PCB congeners by egg injection

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, D.J.; Melancon, M.J.; Eisemann, J.D.; Klein, P.N. [National Biological Service, Laurel, MD (United States). Patuxent Environmental Science Center

    1995-12-31

    The utility of egg injection studies for predicting potential embryotoxicity of PCBs and TCDD compares favorably with feeding studies. The effects of PCB congeners 3,3{prime}4,4{prime}-tetraCB (PCB 77), 2,3,3{prime},4,4{prime}-pentaCB (PCB 105), 3,3{prime},4,4{prime},5-pentaCB (PCB 126) and 2,2{prime},4,4{prime},5,5{prime}-hexaCB (PCB 153) were examined on embryonic development in chickens (Gallus gallus), northern bobwhite (Colinus virginianus), American kestrels (Falco sparverius), and common terns (Sterna hirundo) through hatching following air cell injections on day 4. The estimated LD{sub 50}s for these congeners in chickens were approximately 0.4 ppb, 2.6 ppb, 3326 ppb, and greater than 14,000 ppb, respectively; low effect levels (10--20% embryonic mortality) were 0.2 ppb, 1.2 ppb, 900 ppb, and 14,000 ppb respectively. The estimated LD{sub 50} for PCB 126 was 48 ppb for bobwhite, 65 ppb for American kestrels, and 104 ppb for common terns. The estimated LD{sub 50} for PCB 77 was 688 ppb for American kestrels. one or more hepatic microsomal cytochrome P450-linked monooxygenases including ethoxyresorufin-O-deethylase was assayed for each species. For PCB 126, the order of responsiveness of cytochrome P450 induction was: chicken > common tern > American kestrel > bobwhite, with chicken being approximately 100 times more responsive than common tern. These values are compared to existing Toxic Equivalency Factors (TEFs) including bioassay-derived ones.

  5. Switching from high-fat to low-fat diet normalizes glucose metabolism and improves glucose-stimulated insulin secretion and insulin sensitivity but not body weight in C57BL/6J mice.

    Science.gov (United States)

    Agardh, Carl-David; Ahrén, Bo

    2012-03-01

    Environmental factors such as a high-fat diet contribute to type 2 diabetes and obesity. This study examined glycemia, insulin sensitivity, and β-cell function after switching from a high-fat diet to a low-fat diet in mice. C57BL/6J mice were fed a high-fat diet or low-fat diet for 18 months, after which mice on the high-fat diet either maintained this diet or switched to a low-fat diet for 4 weeks. Body weight and glucose and insulin responses to intraperitoneal glucose were determined. Insulin secretion (insulinogenic index: the 10-minute insulin response divided by the 10-minute glucose level) and insulin sensitivity (1 divided by basal insulin) were determined. After 18 months on a high-fat diet, mice had glucose intolerance, marked hyperinsulinemia, and increased body weight compared to mice on a low-fat diet (P diet to low-fat diet normalized glucose tolerance, reduced but not normalized body weight (P diet to low-fat diet normalizes glucose tolerance and improves but not normalizes insulin secretion and insulin sensitivity. These effects are more pronounced than the reduced body weight.

  6. In utero depletion of fetal hematopoietic stem cells improves engraftment after neonatal transplantation in mice

    OpenAIRE

    Derderian, S. Christopher; Togarrati, P. Priya; King, Charmin; Moradi, Patriss W.; Reynaud, Damien; Czechowicz, Agnieszka; Weissman, Irving L; MacKenzie, Tippi C.

    2014-01-01

    In utero injection of an antibody against the c-Kit receptor can effectively deplete host HSCs in mice.In utero depletion of host HSCs leads to significantly increased engraftment after neonatal congenic hematopoietic cell transplantation.

  7. Half-life of each dioxin and PCB congener in the human body

    Energy Technology Data Exchange (ETDEWEB)

    Ogura, Isamura [National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan)

    2004-09-15

    It is well known that dioxin and PCB congeners accumulate in the human body. For assessing their toxicological risk, it is important to know the half-life of each congener in the human body. This study summarizes the overall half-lives of congeners in humans as reported in the literature, and compares them with the half-lives due to fecal and sebum excretions, as estimated by data on the concentrations of congeners in feces and sebum in the literature. In addition, the overall half-lives of congeners for the general Japanese population were estimated from the data on dietary intakes and concentrations in the human body reported by the municipalities.

  8. Normalization of nano-sized TiO2-induced clastogenicity, genotoxicity and mutagenicity by chlorophyllin administration in mice brain, liver, and bone marrow cells.

    Science.gov (United States)

    El-Ghor, Akmal A; Noshy, Magda M; Galal, Ahmad; Mohamed, Hanan Ramadan H

    2014-11-01

    The intensive uses of titanium dioxide (TiO2) nanoparticles in sunscreens, toothpaste, sweats, medications, etc. making humans exposed to it daily by not little amounts and also increased its risks including genotoxicity. Thus, the present study was designed as one way to reduce nano-titanium-induced clastogenicity, genotoxicity, and mutagenicity in mice by co-administration of the free radical scavenger chlorophyllin (CHL). In addition, markers of oxidative stress were detected to shed more light on mechanism(s) underlying nano-sized TiO2 genotoxicity. Male mice were exposed to multiple injection into the abdominal cavity for five consecutive days with either CHL (40 mg/kg bw/day), or each of three dose levels of nano-sized TiO2 (500, 1000, or 2000 mg/kg bw/day) alone, or both simultaneously and sacrificed by cervical dislocation 24 h after the last treatment. After CHL co-administration, the observed dose-dependent genotoxicity of TiO2 nanoparticles indicated by the significant elevations in frequencies of both micronuclei and DNA damage induction was significantly decreased and returned to the negative control level. The observed induced mutations in p53 exons 5, 7, & 8 and 5 & 8 in the liver and brain, respectively, were declined in most cases. Moreover, CHL significantly decreased hepatic malondialdehyde level and significantly increased glutathione level and superoxide dismutase, catalase, and glutathione peroxidase activities that were significantly disrupted in animal groups treated with nano-TiO2 alone. In conclusion, the evidenced in vivo genotoxicity of nano-TiO2 in the present study was normalized after CHL co-administration which supports the previously suggested oxidative stress as the possible mechanism for titanium toxicity.

  9. Photoprotective Potential of Glycolic Acid by Reducing NLRC4 and AIM2 Inflammasome Complex Proteins in UVB Radiation-Induced Normal Human Epidermal Keratinocytes and Mice.

    Science.gov (United States)

    Hung, Sung-Jen; Tang, Sheau-Chung; Liao, Pei-Yun; Ge, Jheng-Siang; Hsiao, Yu-Ping; Yang, Jen-Hung

    2017-02-01

    Exposure to UVB radiation induces inflammation and free radical-mediated oxidative stress through reactive oxygen species (ROS) that play a crucial role in the induction of skin cancer. Glycolic acid (GA) is frequently used in cosmetics and dermatology. The aim of the study was to analyze the photoprotective mechanisms through which GA retards UVB-induced ROS accumulation and inflammation in normal human epidermal keratinocytes (NHEKs) and mice skin, respectively. NHEK cell line and C57BL/6J mice were treated with GA (0.1 or 5 mM) for 24 h followed by UVB irradiation. ROS accumulation, DNA damage, and expression of inflammasome complexes (NLRP3, NLRC4, ASC, and AIM2) were measured in vitro. Epidermal thickness and inflammasome complex proteins were analyzed in vivo. GA significantly prevented UVB-induced loss of skin cell viability, ROS formation, and DNA damage (single and double strands DNA break). GA suppressed the mRNA expression levels of NLRC4 and AIM2 among the inflammasome complexes. GA also blocked interleukin (IL)-1β by reducing the activity of caspase-1 in the NHEKs. Treatment with GA (2%) inhibited UVB-induced inflammation marker NLRC4 protein levels in mouse dorsal skin. The photoprotective activity of GA was ascribed to the inhibition of ROS formation and DNA damage, as well as a reduction in the activities of inflammasome complexes and IL-1β. We propose that GA has anti-inflammatory and photoprotective effects against UVB irradiation. GA is potentially beneficial to the protection of human skin from UV damage.

  10. Relationship of Enhanced Butyrate Production by Colonic Butyrate-Producing Bacteria to Immunomodulatory Effects in Normal Mice Fed an Insoluble Fraction of Brassica rapa L.

    Science.gov (United States)

    Tanaka, Sachi; Yamamoto, Kana; Yamada, Kazuki; Furuya, Kanon; Uyeno, Yutaka

    2016-05-01

    This study was performed to determine the effects of feeding a fiber-rich fraction of Brassica vegetables on the immune response through changes in enteric bacteria and short-chain fatty acid (SCFA) production in normal mice. The boiled-water-insoluble fraction of Brassica rapa L. (nozawana), which consists mainly of dietary fiber, was chosen as a test material. A total of 31 male C57BL/6J mice were divided into two groups and housed in a specific-pathogen-free facility. The animals were fed either a control diet or the control diet plus the insoluble B. rapa L. fraction for 2 weeks and sacrificed to determine microbiological and SCFA profiles in lower-gut samples and immunological molecules. rRNA-based quantification indicated that the relative population of Bacteroidetes was markedly lower in the colon samples of the insoluble B. rapa L. fraction-fed group than that in the controls. Populations of the Eubacterium rectale group and Faecalibacterium prausnitzii, both of which are representative butyrate-producing bacteria, doubled after 2 weeks of fraction intake, accompanying a marginal increase in the proportion of colonic butyrate. In addition, feeding with the fraction significantly increased levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and tended to increase splenic regulatory T cell numbers but significantly reduced the population of cells expressing activation markers. We demonstrated that inclusion of the boiled-water-insoluble fraction of B. rapa L. can alter the composition of the gut microbiota to decrease the numbers of Bacteroidetes and to increase the numbers of butyrate-producing bacteria, either of which may be involved in the observed shift in the production of splenic IL-10. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Normalization of the lymph node T cell stromal microenvironment in lpr/lpr mice is associated with SU5416-induced reduction in autoantibodies.

    Directory of Open Access Journals (Sweden)

    Susan Chyou

    Full Text Available The vascular-stromal elements of lymph nodes can play important roles in regulating the activities of the lymphocytes within. During model immune responses, the vascular-stromal compartment has been shown to undergo proliferative expansion and functional alterations. The state of the vascular-stromal compartment and the potential importance of this compartment in a spontaneous, chronic model of autoimmunity have not been well studied. Here, we characterize the vascular expansion in MRL-lpr/lpr lymph nodes and attempt to ask whether inhibiting this expansion can interfere with autoantibody generation. We show that characteristics of vascular expansion in enlarging MRL-lpr/lpr lymph nodes resemble that of the VEGF-dependent expansion that occurs in wild-type mice after model immunization. Surprisingly, treatment with SU5416, an inhibitor of VEGF and other receptor tyrosine kinases, did not have sustained effects in inhibiting vascular growth, but attenuated the anti-dsDNA response and altered the phenotype of the double negative T cells that are expanded in these mice. In examining for anatomic correlates of these immunologic changes, we found that the double negative T cells are localized within ectopic follicles around a central B cell patch and that these T cell-rich areas lack the T zone stromal protein ER-TR7 as well as other elements of a normal T zone microenvironment. SU5416 treatment disrupted these follicles and normalized the association between T zone microenvironmental elements and T cell-rich areas. Recent studies have shown a regulatory role for T zone stromal elements. Thus, our findings of the association of anti-dsDNA responses, double negative T cell phenotype, and altered lymphocyte microenvironment suggest the possibility that lymphocyte localization in ectopic follicles protects them from regulation by T zone stromal elements and functions to maintain autoimmune responses. Potentially, altering the lymphocyte microenvironment

  12. Selective reconstitution of T lymphocyte subsets in scid mice

    DEFF Research Database (Denmark)

    Reimann, J; Rudolphi, A; Claesson, Mogens Helweg

    1991-01-01

    The 'empty' splenic T-cell compartment of young scid mice was partially and selectively reconstituted by low numbers of adoptively transferred congenic (C.B-17, BALB/c) or semi-allogeneic (dm2), but not completely allogeneic (C57BL/6) CD4+ T cells from adult donor mice. Under the same experimental...

  13. A modeling approach to compare ΣPCB concentrations between congener-specific analyses

    Science.gov (United States)

    Gibson, Polly P.; Mills, Marc A.; Kraus, Johanna M.; Walters, David M.

    2017-01-01

    Changes in analytical methods over time pose problems for assessing long-term trends in environmental contamination by polychlorinated biphenyls (PCBs). Congener-specific analyses vary widely in the number and identity of the 209 distinct PCB chemical configurations (congeners) that are quantified, leading to inconsistencies among summed PCB concentrations (ΣPCB) reported by different studies. Here we present a modeling approach using linear regression to compare ΣPCB concentrations derived from different congener-specific analyses measuring different co-eluting groups. The approach can be used to develop a specific conversion model between any two sets of congener-specific analytical data from similar samples (similar matrix and geographic origin). We demonstrate the method by developing a conversion model for an example data set that includes data from two different analytical methods, a low resolution method quantifying 119 congeners and a high resolution method quantifying all 209 congeners. We used the model to show that the 119-congener set captured most (93%) of the total PCB concentration (i.e., Σ209PCB) in sediment and biological samples. ΣPCB concentrations estimated using the model closely matched measured values (mean relative percent difference = 9.6). General applications of the modeling approach include (a) generating comparable ΣPCB concentrations for samples that were analyzed for different congener sets; and (b) estimating the proportional contribution of different congener sets to ΣPCB. This approach may be especially valuable for enabling comparison of long-term remediation monitoring results even as analytical methods change over time. 

  14. Adenosine Amine Congener as a Cochlear Rescue Agent

    Directory of Open Access Journals (Sweden)

    Srdjan M. Vlajkovic

    2014-01-01

    Full Text Available We have previously shown that adenosine amine congener (ADAC, a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 μg/kg was administered intraperitoneally to Wistar rats (8–10 weeks old at intervals (6–72 hours after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours. Hearing sensitivity was assessed using auditory brainstem responses (ABR before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz. Pharmacokinetic studies demonstrated a short (5 min half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment.

  15. Contrasting patterns of transgenerational plasticity in ecologically distinct congeners.

    Science.gov (United States)

    Sultan, Sonia E; Barton, Kasey; Wilczek, Amity M

    2009-07-01

    Stressful parental environments can influence offspring size and development either adaptively or maladaptively, yet little is known about species' differences in this complex aspect of phenotypic plasticity. We performed a reciprocal split-brood experiment to compare transgenerational plasticity in response to drought stress in two closely related annual plant species. We raised inbred replicate parent plants of eight genotypes per species in dry vs. moist soil to generate offspring of each genetic line that differed only in parental environment, then monitored seedling development in both dry and moist conditions. Individuals of the two species expressed contrasting patterns of transgenerational plasticity for traits important to seedling drought tolerance. In Polygonum persicaria, a weedy generalist found in moist, dry, and variably dry sites, drought-stressed plants produced offspring with longer and more rapidly extending root systems and greater biomass when growing in dry soil. In contrast, in P. hydropiper, a non-weedy congener restricted to moist habitats, the offspring of drought-stressed parents had reduced root system development and seedling biomass in dry soil. In P. persicaria, transgenerational and immediate adaptive plasticity combined to produce drought-adapted seedling phenotypes. These results make clear that characteristic patterns of transgenerational plasticity can contribute to ecological diversity among species.

  16. Increased intracellular Th1 cytokines in scid mice with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Bregenholt, S; Claesson, Mogens Helweg

    1998-01-01

    by intracellular staining. A 4-5-fold increase in the fraction of IFN-gamma-producing CD4+ lamina propria T cells was found in moderately and severely diseased mice when compared to healthy congenic C.B-17 control mice. The number of IL-2-producing T cells was increased by approximately 2-fold when comparing mice...

  17. Sorption behaviors of a persistent toxaphene congener on marine sediments under different physicochemical conditions.

    Science.gov (United States)

    Soubaneh, Youssouf Djibril; Gagné, Jean-Pierre; Lebeuf, Michel; Gouteux, Bruno; Nikiforov, Vladimir; Awaleh, Mohamed Osman

    2014-11-01

    Sorptive processes are important parameters affecting the mobility, availability and fate of persistent organic pollutants (POPs), such as toxaphene, in aquatic systems. The sorption and desorption behaviors of the B7-1450, a stable toxaphene congener in environment, on marine sediment was studied under different temperature and salinity conditions to better understand the B-1450 distribution in estuarine systems. The data were fitted to different sorption models to characterize sorption behaviors by evaluating sorption coefficients and sequestrated fraction of B7-1450 on sediments. High carbon-normalized sorption coefficients (Koc) of the B7-1450 were observed with values ranging from 3.2×104 to 6.0×104 mL g(-1) under experimental conditions. The data showed an increase of B7-1450 sorption coefficients with the salinity and a decrease with temperature. These investigations indicate that B7-1450 is three times more sequestred on sediments in cold (2°C, 30 psu) than in warm marine conditions (20°C, 30 psu). These results suggest that the mobility and bioavailable of B7-1450 or other POPs from the sediments could be less important in cold marine comparatively in warm marine and warm freshwater media. As a result of climate changes, the warming of mid and high latitudes coastal waters could enhance the mobility of POPs.

  18. Modular methodology for determination of polychlorinated biphenyls in soil as Aroclors and individual congeners

    Energy Technology Data Exchange (ETDEWEB)

    Donnelly, J.R.; Grange, A.H.; Herron, N.R. [Lockheed Environmental Systems & Technologies Co., Las Vegas, NV (United States)] [and others

    1996-07-01

    A comprehensive screening and confirmatory method was developed for monitoring polychlorinated biphenyls (PCBs), both as Aroclors and as individual congeners. This approach incorporates extraction, extract cleanup, and analysis modules designed to match cost, time, and data quality requirements. Soxhlet, sonication, supercritical fluid, and accelerated solvent extractions were evaluated. Carbon chromatographic cleanup procedures were used for separation of congeners on the basis of ortho substitutions, which permitted calculation of toxicity equivalents. Individual congener determinations, congener total histograms, and peak comparison techniques for Aroclor identification were elaborated by using high and low resolution mass spectrometric data. A screening procedure based on immunoassay using the Ohmicron PCB RaPID Assay{trademark} kit gave results comparable to those obtained by gas chromatography with electron capture detection in the range 0.40-230 ppm, when the appropriate Aroclor calibrator was used. 21 refs., 3 figs., 4 tabs.

  19. The Identification of Congeners and Aliens by Drosophila Larvae.

    Directory of Open Access Journals (Sweden)

    Francisco Del Pino

    Full Text Available We investigated the role of Drosophila larva olfactory system in identification of congeners and aliens. We discuss the importance of these activities in larva navigation across substrates, and the implications for allocation of space and food among species of similar ecologies. Wild type larvae of cosmopolitan D. melanogaster and endemic D. pavani, which cohabit the same breeding sites, used species-specific volatiles to identify conspecifics and aliens moving toward larvae of their species. D. gaucha larvae, a sibling species of D. pavani that is ecologically isolated from D. melanogaster, did not respond to melanogaster odor cues. Similar to D. pavani larvae, the navigation of pavani female x gaucha male hybrids was influenced by conspecific and alien odors, whereas gaucha female x pavani male hybrid larvae exhibited behavior similar to the D. gaucha parent. The two sibling species exhibited substantial evolutionary divergence in processing the odor inputs necessary to identify conspecifics. Orco (Or83b mutant larvae of D. melanogaster, which exhibit a loss of sense of smell, did not distinguish conspecific from alien larvae, instead moving across the substrate. Syn97CS and rut larvae of D. melanogaster, which are unable to learn but can smell, moved across the substrate as well. The Orco (Or83b, Syn97CS and rut loci are necessary to orient navigation by D. melanogaster larvae. Individuals of the Trana strain of D. melanogaster did not respond to conspecific and alien larval volatiles and therefore navigated randomly across the substrate. By contrast, larvae of the Til-Til strain used larval volatiles to orient their movement. Natural populations of D. melanogaster may exhibit differences in identification of conspecific and alien larvae. Larval locomotion was not affected by the volatiles.

  20. The Identification of Congeners and Aliens by Drosophila Larvae

    Science.gov (United States)

    Del Pino, Francisco; Jara, Claudia; Pino, Luis; Medina-Muñoz, María Cristina; Alvarez, Eduardo; Godoy-Herrera, Raúl

    2015-01-01

    We investigated the role of Drosophila larva olfactory system in identification of congeners and aliens. We discuss the importance of these activities in larva navigation across substrates, and the implications for allocation of space and food among species of similar ecologies. Wild type larvae of cosmopolitan D. melanogaster and endemic D. pavani, which cohabit the same breeding sites, used species-specific volatiles to identify conspecifics and aliens moving toward larvae of their species. D. gaucha larvae, a sibling species of D. pavani that is ecologically isolated from D. melanogaster, did not respond to melanogaster odor cues. Similar to D. pavani larvae, the navigation of pavani female x gaucha male hybrids was influenced by conspecific and alien odors, whereas gaucha female x pavani male hybrid larvae exhibited behavior similar to the D. gaucha parent. The two sibling species exhibited substantial evolutionary divergence in processing the odor inputs necessary to identify conspecifics. Orco (Or83b) mutant larvae of D. melanogaster, which exhibit a loss of sense of smell, did not distinguish conspecific from alien larvae, instead moving across the substrate. Syn97CS and rut larvae of D. melanogaster, which are unable to learn but can smell, moved across the substrate as well. The Orco (Or83b), Syn97CS and rut loci are necessary to orient navigation by D. melanogaster larvae. Individuals of the Trana strain of D. melanogaster did not respond to conspecific and alien larval volatiles and therefore navigated randomly across the substrate. By contrast, larvae of the Til-Til strain used larval volatiles to orient their movement. Natural populations of D. melanogaster may exhibit differences in identification of conspecific and alien larvae. Larval locomotion was not affected by the volatiles. PMID:26313007

  1. Use of herbarium data to evaluate weediness in five congeners.

    Science.gov (United States)

    Hanan-A, Ana M; Vibrans, Heike; Cacho, N Ivalú; Villaseñor, José L; Ortiz, Enrique; Gómez-G, Vinicio A

    2015-01-01

    It is often desirable to quantify a plant's relative weediness or synanthropy, that is, the degree to which a species associates with human-caused disturbance, in order to study and understand the biology, ecology and evolution of weeds and invasive plants. Herbarium specimens are among the most accessible and verifiable sources of data on distribution and habitat. However, the habitat distribution of species may not be reflected accurately by herbarium specimen data, due to well-known biases in plant collection. Here, we assess how well herbarium specimens reflect species' weediness, when compared with direct field surveys. We used five species of Melampodium (Asteraceae) and classified their degree of weediness with a modification of Nuorteva's synanthropy index, based on herbarium specimens. We then modelled the distribution of our focal species in Mexico using MaxEnt and identified a polygon of ∼3000 km(2) in the state of Nayarit, Mexico, where there was a high probability of finding all five species. Systematic field searches in the target area documented all visible populations of four species along major and minor roads. Then we, again, classified their degree of weediness with the synanthropy index, based now on field data, and compared. We found that herbarium data were an accurate predictor of a species' weediness relative to its congeners despite the well-documented skew of herbarium data towards natural areas, which our data reflected as well. So, herbarium data can be used to classify species' weediness relative to each other, but not in absolute terms, if the specimens were correctly identified and none of the species were subject to particular collection bias. This study is the first attempt to compare herbarium and field data on this subject and may be relevant for other types of investigations based on herbarium data. Our work also highlights the usefulness of distribution models based on herbarium specimens.

  2. Blood glucose level and other biochemical changes induced in normal mice by oral Traditional Chinese Medicine complex for diabetes (TCM-D™

    Directory of Open Access Journals (Sweden)

    Donald Koh Fook Chen

    2012-12-01

    Full Text Available Background: A number of Traditional ChineseMedicine (TCM preparations are being used for thetreatment of diabetes mellitus. Some componentsof these preparations have biochemical effects otherthan those of lowering blood glucose and indeed havebeen used for other medical indications in traditionalpractice. The primary objective of the study was todetermine the effect of the oral mixture of TraditionalChinese Medicine for diabetes (TCM-D™ complex onblood glucose level and the biochemical changes if any,on the liver (ALT, AST, gamma-GT, albumin, globulinand renal (blood creatinine, urea functions in normalmice. The oral mixture is an aqueous extract of four wellknowntraditional Chinese medicinal herbs and consistsof Trichosanthes kirilowii Maxim., Paeonia lactiflora Pall.,Glycyrrhiza uranlensis Fisch., and Panax ginseng (redCA Meyer in the proportion of 36%, 28%, 18%, and18% respectively of the dry weight. These herbs havebeen shown to have blood glucose lowering activity andhave been used for other traditional medicinal purposes.The safety of the combination was evaluated in thepresent study.Methods: Experimental Balb/c mice were treated orallyvia gastric tube with the extract at daily doses equivalentto 1 and 10 times the recommended human dose for8 weeks. Blood glucose and other biochemical profileswere monitored at pre-treatment and monthly posttreatmentuntil killed.Results: When compared to pre-treatment levels, theblood glucose levels were significantly lower in treatedanimals compared to those in the control group. Atthe recommended TCM-D™ dose the levels in treatedanimals were significantly lower than that of controlanimals and at pre-treatment. When compared withpre-treatment, the glucose levels were lowest at Week8 of treatment, the mean levels being 111.23%, 83.32%and 70.33% in control, and in animals given 1 x and10 x the recommended TCM-D™ dosage respectively.The blood glucose lowering effect was also associatedwith a significant

  3. Anti-aging effects of Piper cambodianum P. Fourn. extract on normal human dermal fibroblast cells and a wound-healing model in mice

    Directory of Open Access Journals (Sweden)

    Lee H

    2016-07-01

    that PPF-treated cells displayed dose-dependent increase in messenger RNA expression levels of collagen, elastin, and hyaluronan synthase-2 and decreased expression levels of matrix metalloproteinase-1 aging gene. PPF treatment led to decreased production of reactive oxygen species in cells subjected to ultraviolet irradiation. Furthermore, PPF extract showed positive wound-healing effects in mice.Conclusion: This study demonstrated the anti-aging and wound-healing effects of PPF extract. Therefore, PPF extract represents a promising new therapeutic agent for anti-aging and wound-healing treatments. Keywords: PPF extract, anti-aging, wound healing, antioxidant, ROS, normal human dermal fibroblasts

  4. Comparative biodistribution of potential anti-glioblastoma conjugates [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF in normal mice.

    Science.gov (United States)

    Tolmachev, Vladimir; Orlova, Anna; Wei, Qichun; Bruskin, Alexander; Carlsson, Jörgen; Gedda, Lars

    2004-08-01

    EGF-receptors (EGFR) are overexpressed in gliomas, as well as in tumors of breast, lung, and urinary bladder. For this reason, EGFR may be an attractive target for both visualization and therapy of malignant tumors using radioactive nuclides. Natural ligand of EGFR, epidermal growth factor (EGF) is a small 53-amino-acid protein. Low molecular weight of EGF may enable better intratumoral penetration in comparison to antibodies. [111In]DTPA-EGF was proposed for the targeting of glioblastoma and breast cancer, and its tumor-seeking properties were confirmed in animal studies. The aim of this study was to evaluate how the substitution of heptadentate DTPA for octadentate benzyl-DTPA (Bz-DTPA) effects the biodistribution of indium-labeled human EGF (hEGF) in normal NMRI mice. [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF, obtained by the coupling of ITC-benzyl-DTPA to hEGF, were injected into the tail vein. At 0.5, 1, 4, and 24 hours postinjection, the animals were sacrificed, and radioactivity in different organs was measured. The blood clearance of both conjugates was fast. The uptake of both conjugates in the liver, spleen, stomach, pancreas, intestines, and submaxillary gland was most likely receptor-mediated. The uptake in a majority of organs was similar. However, indium uptake in the case of [111In]DTPA-hEGF was significantly higher in the kidneys and bones. In conclusion, [111In]Bz-DTPA-hEGF seems to have more favourable in vivo distribution in comparison to [111In]DTPA-hEGF.

  5. Dipolar cortico-muscular electrical stimulation: a novel method that enhances motor function in both - normal and spinal cord injured mice

    Directory of Open Access Journals (Sweden)

    Ahmed Zaghloul

    2010-09-01

    Full Text Available Abstract Background Electrical stimulation of the central and peripheral nervous systems is a common tool that is used to improve functional recovery after neuronal injury. Methods Here we described a new configuration of electrical stimulation as it was tested in anesthetized control and spinal cord injury (SCI mice. Constant voltage output was delivered through two electrodes. While the negative voltage output (ranging from -1.8 to -2.6 V was delivered to the muscle via transverse wire electrodes (diameter, 500 μm located at opposite ends of the muscle, the positive output (ranging from + 2.4 to +3.2 V was delivered to the primary motor cortex (M1 (electrode tip, 100 μm. The configuration was named dipolar cortico-muscular stimulation (dCMS and consisted of 100 pulses (1 ms pulse duration, 1 Hz frequency. Results In SCI animals, after dCMS, cortically-elicited muscle contraction improved markedly at the contralateral (456% and ipsilateral (457% gastrocnemius muscles. The improvement persisted for the duration of the experiment (60 min. The enhancement of cortically-elicited muscle contraction was accompanied by the reduction of M1 maximal threshold and the potentiation of spinal motoneuronal evoked responses at the contralateral (313% and ipsilateral (292% sides of the spinal cord. Moreover, spontaneous activity recorded from single spinal motoneurons was substantially increased contralaterally (121% and ipsilaterally (54%. Interestingly, spinal motoneuronal responses and muscle twitches evoked by the test stimulation of non-treated M1 (received no dCMS were significantly enhanced as well. Similar results obtained from normal animals albeit the changes were relatively smaller. Conclusion These findings demonstrated that dCMS could improve functionality of corticomotoneuronal pathway and thus it may have therapeutic potential.

  6. Effect of selection for growth on normal and reduced protein diets on weight gain, feed intake, feed efficiency and body composition in mice.

    Science.gov (United States)

    Nielsen, V H; Korsgaard, I R

    2006-12-01

    Mice selected for weight gain from 3 to 9 weeks of age on a normal (N) protein diet containing 19.3% protein and a reduced (R) protein diet with 5.1% protein were reared on both diets in generations 7 and 9. The lines NH, NC, NL, RH, RC and RL (H, high; C, control; L, low) were tested for weight gain on diet N and R and for feed intake and feed efficiency on diet N in generation 7. In generation 9, the lines were tested for body composition traits (fat, protein and water percentage) at 3, 6, 9 and 12 weeks of age on both diets. A significant (p < 0.0001) genotype x environment interaction for growth rate was observed in generation 7. Weight gain at both the protein levels was best improved by selection at the protein level itself. Furthermore, the ranking of the lines on diet N was similar for weight gain, feed intake and feed efficiency. In generation 9 at 9 weeks of age, the ranking of the lines for fat percentage was equal to the ranking for weight gain in generation 7 on both test-diets. The association between weight gain and protein or water percentage was less pronounced, particularly on diet R. These results suggest that the largest genetic improvement in growth rate is obtained when the protein content of the feed is the same in selection and production. However, when selection is carried out in one environment while the animals have to perform under conditions with varying nutrient protein contents, selection in an inferior environment may be advantageous.

  7. A GCMSD/ECD method for the simultaneous determination of toxaphene and toxaphene congeners.

    Science.gov (United States)

    Maceachen, D Cameron; Cocks, Nigel

    2002-10-01

    The methodology presented combines mass selective detection technology for routine automated total toxaphene determinations with electron capture detection confirmation of congener results. Total toxaphene values were calculated using a custom developed series of data analysis macroinstructions (macros) that eliminate potential interferences and collate peak areas. These macros create multi-level calibration tables with results automatically corrected for surrogate and performance standards. It is possible to produce congener data that provides results from both detectors in one report from a single injection.

  8. Human liver morphine UDP-glucuronyl transferase enantioselectivity and inhibition by opioid congeners and oxazepam.

    OpenAIRE

    Wahlström, A; Pacifici, G. M.; Lindström, B; Hammar, L.; Rane, A.

    1988-01-01

    1. Morphine uridine diphosphate glucuronyl transferase (UDP-GT) was studied in human liver microsomes. The (-)- and (+)-morphine enantiomers were used as substrates and inhibitors, such as oxazepam and various opioid congeners were employed to characterize the different glucuronidation pathways. The kinetics of the oxazepam inhibition were studied in the rat liver. 2. The overall glucuronidation of (+)-morphine was higher than that of (-)-morphine. The morphine congeners tested, potently inhi...

  9. Production of WTC.ZI-zi rat congenic strain and its pathological and genetic analyses.

    Science.gov (United States)

    Kuramoto, T; Yamasaki, K; Kondo, A; Nakajima, K; Yamada, M; Serikawa, T

    1998-04-01

    A new rat congenic strain, WTC.ZI-zi, was produced after eleven generations of backcrossing between ZI strain as a donor strain and WTC strain as an inbred partner. WTC.ZI-zi/zi homozygous rats generally exhibit more conspicuous body tremor and much earlier occurrence of flaccid paresis than the original ZI strain. The average life span of the congenic strain is approximately nine months, which is also much shorter than that of the original ZI strain. Pathological analysis of the central nervous system of the congenic strain revealed more aggravated vacuolation and hypomyelination than in the original ZI strain. Establishment of the genetic profile with microsatellite markers showed that the congenic strain was genetically almost identical to the WTC strain except for a small chromosome segment bearing the zitter gene. Analysis of markers in this region implied that the length of the donor segment was approximately 13.4 centimorgans which corresponded to 0.65% of the total genome. Thus, these results suggested that expressional alterations of zitter gene were due to replacement of the genetic background from the original ZI strain to the WTC strain. Furthermore, the WTC.ZI-zi congenic strain could provide a refined tool for the analysis of zitter mutation, because the congenic strain has a strict control strain, WTC, and the length of the donor chromosome is genetically defined.

  10. Net trophic transfer efficiencies of polychlorinated biphenyl congeners to lake whitefish (Coregonus clupeaformis) from their food

    Science.gov (United States)

    Madenjian, C.P.; O'Connor, D.V.; Rediske, R.R.; O'Keefe, J. P.; Pothoven, S.A.

    2008-01-01

    Lake whitefish (Coregonus clupeaformis) were fed rainbow smelt (Osmerus mordax) in four laboratory tanks over a 133-d experiment. At the start of the experiment, 10 to 14 of the fish in each tank were sacrificed, and the concentrations of 40 polychlorinated biphenyl (PCB) congeners within these fish were determined. Polychlorinated biphenyl congener concentrations were also determined in the 15 lake whitefish remaining in each of the four tanks at the end of the experiment as well as in the rainbow smelt fed to the lake whitefish. Each lake whitefish was weighed at the start and the end of the experiment, and the amount of food eaten by the lake whitefish during the experiment was tracked. Using these measurements, net trophic transfer efficiency (??) from the rainbow smelt to the lake whitefish in each of the four tanks was calculated for each of the 40 PCB congeners. Results showed that ?? decreased exponentially as log KOW for the congeners increased from 6 to 8. Further, ?? averaged 0.70 for the tetrachloro congeners but averaged only 0.45 for the higher chlorinated congeners. ?? 2008 SETAC.

  11. Modulation of total IgE levels in serum of normal and athymic nude BALB/c mice by cells and exogenous antigenic stimulation

    NARCIS (Netherlands)

    Savelkoul, H.F.J.; Akker, van den T.W.; Soeting, P.W.C.; Oudenaren, van A.; Benner, R.

    1989-01-01

    Several different grades of T-system impairment were studied for their effects on the total serum IgE concentration in BALB/c mice. Homozygous athymic nu/nu mice and their heterozygous nu/ littermates were compared for serum IgE levels while kept under either barrier-maintained or conventional condi

  12. Deficient CD4+ T cell priming and regression of CD8+ T cell functionality in virus-infected mice lacking a normal B cell compartment

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Kauffmann, Susanne Ørding; Thomsen, Allan Randrup

    2003-01-01

    precedes recrudescence of detectable virus, indicating that the T cell defect is not simply a secondary event due to virus buildup resulting from the failure of B(-/-) mice to produce neutralizing Abs. In contrast with CD8(+) T cells, which initially respond almost as in wild-type mice, the priming...

  13. Analysis of "total toxaphene" and selected single congeners in biota by ion trap HRGC-EI-MS/MS using congener-optimized parent ion dissociations.

    Science.gov (United States)

    Skopp, Sonja; Oehme, Michael; Chu, Fong Lam; Yeboah, Faustinus; Chan, Hing Man

    2002-06-15

    A method for the quantification of selected toxaphene congeners as well as "total toxaphene" was developed based on electron ionization (EI) tandem (MS/MS) ion trap mass spectrometry (MS) and a combination of fragment ion dissociations. Congeners were separated by high-resolution gas chromatography. Compared to conventional EI low-resolution MS, a 5-20-fold gain in sensitivity could be obtained for octa- or nonachlorinated compounds such as toxaphene #26 and #62 (according to Parlar nomenclature), allowing for their detection in the low picogram range in biota. In addition, response factors for important congeners such as #26, #32, #40/41, #42, #44, #50, and #62 deviated not more than a factor of 2, which is much less as compared to negative ion chemical ionization. This reduces the risk for systematic errors when determining total toxaphene on the basis of a limited number of reference compounds or the technical mixture. Furthermore, chlordanes and polychlorinated biphenyls did not interfere when applying the proposed MS/MS technique. The applicability of the method was tested by determining both total toxaphene and levels of selected congeners in six Arctic wildlife samples collected from Nunavut, Canada, as well as by repetitive analyses of the SRM 1588 certified reference material.

  14. Levels, congener profile and inventory of polychlorinated biphenyls in sediment from the Songhua River in the vicinity of cement plant, China: a case study.

    Science.gov (United States)

    Cui, Song; Fu, Qiang; Li, Yi-Fan; Li, Wen-Long; Li, Tian-Xiao; Wang, Min; Xing, Zhen-Xiang; Zhang, Lu-Ji

    2016-08-01

    This study investigated the contamination levels, homologue, and congener profiles and evaluated the residue inventory of polychlorinated biphenyls (PCBs) in sediment of the Songhua River in the vicinity of cement plant. The total concentration of detected 35 PCB congeners ranged from 1.12 to 2.19 ng/g dry weight (dw) in sediment, with a mean value of 1.56 ng/g dw, and the concentration of PCBs decreased in the following order: the downstream > cement plant > upstream. The results of total organic carbon (TOC)-normalized PCB concentrations indicate that the sediments have low potential ecological risk in this area. The study results on homologue and congener of PCBs show that the emissions from cement production could be the major sources of PCBs in sediment, and the low-chlorinated PCBs will be exchanged among air, water, and sediment with increasing temperature during summer and flow to downstream with water during the wet season. The spatial density and total burden of PCBs in the surface sediments were 17.2 ng/cm(2) and 1.2 kg, respectively. To our knowledge, this study is the first to explore the pollution characteristics of unintentionally produced PCB emissions from cement industry by means of monitoring sediment samples.

  15. Role of splenic stroma in the action of bacterial lipopolysaccharides on radiation mortality: a study in mice carrying the Slsup(j) allele

    Energy Technology Data Exchange (ETDEWEB)

    Ploemacher, R.E.; Brons, N.H.C.

    1987-01-01

    Slsup(j)/+ mice display a slight macrocytic anemia due to a defect in their hamopoietic organ stroma. They have a deficient endogenous spleen colony (CFU-end) formation following sublethal doses of gamma-radiation compared with their normal +/+ littermates, which is likely to be due to the low pre-irradiation CFU-S content of the Slsup(j)/+ spleen. CFU-S in these congenic mice do not differ in their sensitivity to gamma-irradiation or stem cell-activating factor. While injection of +/+ mice with 10 ..mu..g of lipopolysaccharide-W (LPS) one day prior to irradiation led to a substantial increase in their survival, the survival of Slsup(j)/+ mice was only slightly increased. Irradiation induced a similar dose-related reduction in the numbers of CFU-S in the spleen and femora of LPS-injected Slsup(j)/+ mice compared to similarly treated +/+ mice when measured directly after irradiation. At Day 9 after irradiation injection of LPS led to a significantly higher CFU-end formation and higher numbers of CFU-S and nucleated cells in the Slsup(j)/+ spleens compared to LPS-injected +/+ mice. No such differences in the radioprotective effect of LPS were observed in the +/+ and Slsup(j)/+ mice with respect to the splenic and femoral /sup 59/Fe-incorporation and the femoral CFU-S numbers at Day 9.

  16. Elastin-insufficient mice show normal cardiovascular remodeling in 2K1C hypertension despite higher baseline pressure and unique cardiovascular architecture.

    Science.gov (United States)

    Wagenseil, Jessica E; Knutsen, Russell H; Li, Dean Y; Mecham, Robert P

    2007-07-01

    Mice heterozygous for the elastin gene (ELN(+/-)) show unique cardiovascular properties, including increased blood pressure and smaller, thinner arteries with an increased number of lamellar units. Some of these properties are also observed in humans with supravalvular aortic stenosis, a disease caused by functional heterozygosity of the elastin gene. The arterial geometry in ELN(+/-) mice is contrary to the increased thickness that would be expected in an animal demonstrating hypertensive remodeling. To determine whether this is due to a decreased capability for cardiovascular remodeling or to a novel adaptation of the ELN(+/-) cardiovascular system, we increased blood pressure in adult ELN(+/+) and ELN(+/-) mice using the two-kidney, one-clip Goldblatt model of hypertension. Successfully clipped mice have a systolic pressure increase of at least 15 mmHg over sham-operated animals. ELN(+/+) and ELN(+/-)-clipped mice show significant increases over sham-operated mice in cardiac weight, arterial thickness, and arterial cross-sectional area with no changes in lamellar number. There are no significant differences in most mechanical properties with clipping in either genotype. These results indicate that ELN(+/+) and ELN(+/-) hearts and arteries remodel similarly in response to adult induced hypertension. Therefore, the cardiovascular properties of ELN(+/-) mice are likely due to developmental remodeling in response to altered hemodynamics and reduced elastin levels.

  17. Anti-aging effects of Piper cambodianum P. Fourn. extract on normal human dermal fibroblast cells and a wound-healing model in mice.

    Science.gov (United States)

    Lee, Hyunji; Hong, Youngeun; Kwon, So Hee; Park, Jongsun; Park, Jisoo

    2016-01-01

    Aging of skin is associated with environmental factors such as ultraviolet rays, air pollution, gravity, and genetic factors, all of which can lead to wrinkling of skin. Previous reports suggest that the wound repair is impaired by the aging process and strategies to manipulate the age-related wound healing are necessary in order to stimulate repair. Several traditional plant extracts are well-known for their properties of skin protection and care. Piper cambodianum P. Fourn. (PPF), a member of Piperacecae, is a plant found in Vietnam that might have therapeutic properties. Therefore, the effects of PPF stem and leaf extract on aging process were investigated in vitro and in vivo. PPF extract dissolved in methanol was investigated using Western blotting, real-time quantitative reverse transcription-polymerase chain reaction, flow cytometry, and cell wound-healing assays. We assessed the anti-aging effect of PPF in mouse using the wound-healing assay. The results were analyzed by Student's unpaired t-test; *P<0.05 and **P<0.01 were considered to indicate significant and highly significant values, respectively, compared with corresponding controls. PPF treatment demonstrated in vitro and in vivo anti-aging activity. Western blot analysis of PPF-treated normal human dermal fibroblast cells showed a dose-dependent increase in the expression of extracellular matrix genes such as collagen and elastin, but decreased expression of the aging gene matrix metalloproteinase-3. Quantitative polymerase chain reaction showed that PPF-treated cells displayed dose-dependent increase in messenger RNA expression levels of collagen, elastin, and hyaluronan synthase-2 and decreased expression levels of matrix metalloproteinase-1 aging gene. PPF treatment led to decreased production of reactive oxygen species in cells subjected to ultraviolet irradiation. Furthermore, PPF extract showed positive wound-healing effects in mice. This study demonstrated the anti-aging and wound

  18. Generation of congenic mouse strains by introducing the virus-resistant genes, Mx1 and Oas1b, of feral mouse-derived inbred strain MSM/Ms into the common strain C57BL/6J.

    Science.gov (United States)

    Moritoh, Kanako; Yamauchi, Hideto; Asano, Atsushi; Yoshii, Kentaro; Kariwa, Hiroaki; Takashima, Ikuo; Isoda, Norikazu; Sakoda, Yoshihiro; Kida, Hiroshi; Sasaki, Nobuya; Agui, Takashi

    2009-08-01

    Mx1 (Myxovirus resistance protein) and Oaslb (Oligoadenylate synthetase-1), induced by type 1 interferon (IFN), play a role in early antiviral innate immunity by inhibiting the replication of viruses. In mice, Mx1 and Oas1b confer resistance to the infection of orthomyxoviruses including influenza viruses and flaviviruses including West Nile viruses, respectively. Laboratory mice have been used to study the mechanisms of the pathogenesis of these virus infections; however, it is possible that they are not a suitable model system to study these viruses, since most of the inbred laboratory mouse strains lack both genes. It has been reported that feral mouse-derived inbred strains show resistance to the infection of these viruses due to the presence of intact both genes. In this study, we generated congenic strains in which the Mx or Oas locus of the MSM/Ms (MSM) mouce was introduced to the most widely used mouse strain, C57BL/6J (B6). B6.MSM-Mx mice showed resistance to the infection of influenza virus but not of West Nile virus. On the other hand, B6.MSM-Oas mice showed resistance to the infection of West Nile virus but not of influenza virus. Our results indicate that Mx1 and Oaslb show highly antiviral specificity in mice possessing the same genetic background. Therefore, these congenic mice are useful for not only infection study but also investigation of host defense mechanism to these viruses.

  19. Net trophic transfer efficiencies of polychlorinated biphenyl congeners to lake trout (Salvelinus namaycush) from its prey

    Science.gov (United States)

    Madenjian, Charles P.; David, Solomon R.; Rediske, Richard R.; O’Keefe, James P.

    2012-01-01

    Lake trout (Salvelinus namaycush) were fed bloater (Coregonus hoyi) in eight laboratory tanks over a 135-d experiment. At the start of the experiment, four to nine fish in each tank were sacrificed, and the concentrations of 75 polychlorinated biphenyl (PCB) congeners within these fish were determined. Polychlorinated biphenyl congener concentrations were also determined in the 10 lake trout remaining in each of the eight tanks at the end of the experiment as well as in the bloater fed to the lake trout. Each lake trout was weighed at the start and the end of the experiment, and the amount of food eaten by the lake trout was recorded. Using these measurements, net trophic transfer efficiency (γ) from the bloater to the lake trout in each of the eight tanks was calculated for each of the 75 congeners. Results showed that γ did not vary significantly with the degree of chlorination of the PCB congeners, and γ averaged 0.66 across all congeners. However,γ did show a slight, but significant, decrease as logKOW increased from 6.0 to 8.2. Activity level of the lake trout did not have a significant effect on γ.

  20. Cutting Edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice.

    Science.gov (United States)

    Berger, Scott B; Kasparcova, Viera; Hoffman, Sandy; Swift, Barb; Dare, Lauren; Schaeffer, Michelle; Capriotti, Carol; Cook, Michael; Finger, Joshua; Hughes-Earle, Angela; Harris, Philip A; Kaiser, William J; Mocarski, Edward S; Bertin, John; Gough, Peter J

    2014-06-15

    RIP1 (RIPK1) kinase is a key regulator of TNF-induced NF-κB activation, apoptosis, and necroptosis through its kinase and scaffolding activities. Dissecting the balance of RIP1 kinase activity and scaffolding function in vivo during development and TNF-dependent inflammation has been hampered by the perinatal lethality of RIP1-deficient mice. In this study, we generated RIP1 kinase-dead (Ripk1(K45A)) mice and showed they are viable and healthy, indicating that the kinase activity of RIP1, but not its scaffolding function, is dispensable for viability and homeostasis. After validating that the Ripk1(K45A) mice were specifically protected against necroptotic stimuli in vitro and in vivo, we crossed them with SHARPIN-deficient cpdm mice, which develop severe skin and multiorgan inflammation that has been hypothesized to be mediated by TNF-dependent apoptosis and/or necroptosis. Remarkably, crossing Ripk1(K45A) mice with the cpdm strain protected against all cpdm-related pathology. Together, these data suggest that RIP1 kinase represents an attractive therapeutic target for TNF-driven inflammatory diseases.

  1. Separation of 26 toxaphene congeners and measurement in air particulate matter SRMs compared to technical toxaphene SRM 3067.

    Science.gov (United States)

    Vander Pol, Stacy S; Kucklick, John R; Leigh, Stefan D; Porter, Barbara J; Schantz, Michele M

    2010-05-01

    Toxaphene is a complex technical mixture that has been found ubiquitously in the environment but has caused issues for analysis, especially of individual congeners. This paper reports the elution order of 26 major toxaphene congeners on three gas chromatographic columns. The three different stationary phases generally had similar elution orders for the toxaphene congeners, but fewer co-elutions occurred on a low-bleed, low-polarity column. These congeners (except for two that co-eluted and were not added to the calibration mixture) were examined in air particulate matter standard reference materials (SRMs), 1648a, 1649a, and 1649b as well as SRM 3067 toxaphene in methanol for assignment of reference values. SRM 3067 had mass fractions an order of magnitude greater than the air particulate SRMs, which ranged from 0.568 +/- 0.018 ng g(-1) dry mass (B9-2006 in SRM 1648a) to 12.9 +/- 0.20 ng g(-1) dry mass (B9-715 (P 58) in SRM 1649a). The three air particulate SRMs all had different mass fractions and proportions of congeners relative to the sum of the toxaphene congeners. SRM 3067 may be useful as a technical mixture toxaphene congener calibrant. SRMs 1648a and 1649b will serve as reference materials for the analysis of 21 (three congeners were not included due to values below the detection limit or a potential polychlorinated biphenyl co-elution) toxaphene congeners in atmospheric particulate samples.

  2. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice.

    Science.gov (United States)

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-03-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the effect of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) on food allergy-induced impaired social behaviour and associated deficits in prefrontal dopamine (DA) in mice. Mice were fed either control or n-3 LCPUFA-enriched diet before and during sensitization with whey. Social behaviour, acute allergic skin response and serum immunoglobulins were assessed. Monoamine levels were measured in brain and intestine and fatty acid content in brain. N-3 LCPUFA prevented impaired social behaviour of allergic mice. Moreover, n-3 LCPUFA supplementation increased docosahexaenoic acid (DHA) incorporation into the brain and restored reduced levels of prefrontal DA and its metabolites 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine and homovanillic acid in allergic mice. In addition to these brain effects, n-3 LCPUFA supplementation reduced the allergic skin response and restored decreased intestinal levels of serotonin metabolite 5-hydroxyindoleacetic acid in allergic mice. N-3 LCPUFA may have beneficial effects on food allergy-induced deficits in social behaviour, either indirectly by reducing the allergic response and restoring intestinal 5-HT signalling, or directly by DHA incorporation into neuronal membranes, affecting the DA system. Therefore, it is of interest to further investigate the relevance of food allergy-enhanced impairments in social behaviour in humans and the potential benefits of dietary n-3 LCPUFA supplementation.

  3. Comparison of PCB congener profiles in tissues of PCB-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Kania-Korwel, I.; Ludewig, G.; Robertson, L.W.; Lehmler, H.J. [Dept. of Occupational and Environmental Health, Univ. of Iowa, Iowa City (United States); Hornbuckle, K.C.; Peck, A. [Dept. of Civil and Environmental Engineering, Univ. of Iowa, Iowa City (United States); Sulkowski, W.W. [Dept. of Environmental Chemistry and Technology, Univ. of Silesia, Katowice (Poland)

    2004-09-15

    Information on the congener-specific distribution of PCBs in tissues of laboratory animals after exposure to technical or environmental PCB mixtures is limited. Typically PCB levels and profiles from adipose tissue, liver, blood and occasionally brain are reported. In the work presented here 120 PCB congeners were extracted from 9 tissues of rats exposed to two different PCB mixtures. One mixture was Aroclor 1254, a well studied technical mixture. The second mixture was an environmental mixture obtained after extraction of soil contaminated with Chlorofen, a highly chlorinated Polish PCB mixture. The study was designed to investigate how different chlorination levels and the structure of PCB congeners affect their distribution and total concentration in selected tissues. Principal Component Analysis and Hierarchical Cluster Analysis were employed to compare tissues of Aroclor and soil extract-treated animals.

  4. Cutaneous consequences of inhibiting EGF receptor signaling in vivo: normal hair follicle development, but retarded hair cycle induction and inhibition of adipocyte growth in Egfr(Wa5) mice.

    Science.gov (United States)

    Sugawara, Koji; Schneider, Marlon R; Dahlhoff, Maik; Kloepper, Jennifer E; Paus, Ralf

    2010-03-01

    The epidermal growth factor receptor (EGFR) network is essential for proper development and homeostasis of skin and hair. However, detailed dissection of the role of the EGFR in hair follicle development and cycling have been impaired by the early mortality of EGFR knockout mice. We have studied in Waved-5 mice carrying an antimorphic EGFR allele (Egfr(wa5)), whose product acts as a dominant-negative receptor, whether strongly reduced EGFR signaling impacts on the hair and skin phenotype. Histomorphometry and immunohistochemistry were employed to study hair follicle morphogenesis stages and cycle induction in Waved-5 mice and control littermates during embryonic development and postnatal life. By routine histology and quantitative histomorphometry, no significant abnormalities in the epidermis and in hair follicle morphogenesis were detected, while the initiation of hair follicle cycling was slightly, but significantly retarded. Proliferation and apoptosis of epidermal and hair matrix keratinocytes of Waved-5 mice appeared unaltered. Intriguingly, the thickness of the subcutis and the percentage of proliferating subcutaneous adipocytes were significantly reduced in Waved-5 mice around days P8.5 to P10.5. Although no differences in total body weight gain could be detected, Wa5 mice showed a significant reduction in the percentage of body fat at P8.5. Our results suggest the presence of effective compensatory mechanisms in murine skin in vivo that ensure nearly normal epidermal and hair follicle keratinocyte function despite very low levels of EGFR-mediated signaling. Our unexpected findings of transiently reduced subcutaneous adipose tissue indicate a role for the EGFR in regulating subcutaneous fat. 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Organochlorine pesticides and polychlorinated biphenyl congeners in wild terrestrial mammals from Croatia: Interspecies comparison of residue levels and compositions.

    Science.gov (United States)

    Herceg Romanić, Snježana; Klinčić, Darija; Kljaković-Gašpić, Zorana; Kusak, Josip; Reljić, Slaven; Huber, Đuro

    2015-10-01

    In this pilot study, we investigated levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in the adipose tissues of two free-ranging terrestrial carnivores from Croatia sampled in 2010 and 2011: the brown bear (Ursus arctos; N=32) and the grey wolf (Canis lupus; N=29). Concentrations of ∑OCPs and ΣPCBs ranged from 0.45 to 4.09 ng g(-1) lipid mass (lm) and from 0.93 to 8.52 ng g(-1) lm in brown bear, and from 1.18 to 5.67 ng g(-1) lm and 2.68 to 48.9 ng g(-1) lm in grey wolf adipose tissues, respectively. PCBs were dominant accounting for over 72% of total analyzed persistent organic pollutants (POPs). The sum of six indicator non-dioxin-like PCBs (Σ6IndNDL PCBs) made up 60-93% and 58-85% of the total congener concentrations in brown bears and wolves, respectively. Although the levels of the measured parameters were significantly higher in grey wolves than in bears, the contaminant profiles of the two species were similar, with γ-HCH, HCB, β-HCH and DDE as major OCP contaminants, and PCB-153>PCB-180≈PCB-170>PCB-138 as the dominant congeners. The sum of hexachlorocyclohexanes (ΣHCHs) and 8 toxicologically relevant dioxin-like PCBs (Σ8ToxDL PCBs) was higher in the males than in the females of the brown bear. Concentrations of ΣDDTs, HCB, ΣOCP, ΣPCBs, Σ6IndNDL PCBs, and toxicologically relevant non-dioxin-like PCBs (ΣToxNDL PCBs) were significantly positively correlated with lipid content in the grey wolf. Concentrations of OCPs and PCBs in brown bears and wolves from Croatia were low and normal for large terrestrial mammals.

  6. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice

    NARCIS (Netherlands)

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-01-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the

  7. Dietary long chain n-3 polyunsaturated fatty acids prevent impaired social behaviour and normalize brain dopamine levels in food allergic mice

    NARCIS (Netherlands)

    de Theije, Caroline G M; van den Elsen, Lieke W J; Willemsen, Linette E M; Milosevic, Vanja; Korte-Bouws, Gerdien A H; Lopes da Silva, Sofia; Broersen, Laus M; Korte, S Mechiel; Olivier, Berend; Garssen, Johan; Kraneveld, Aletta D

    2015-01-01

    Allergy is suggested to exacerbate impaired behaviour in children with neurodevelopmental disorders. We have previously shown that food allergy impaired social behaviour in mice. Dietary fatty acid composition may affect both the immune and nervous system. The aim of this study was to assess the eff

  8. NADPH oxidase deficient mice develop colitis and bacteremia upon infection with normally avirulent, TTSS-1- and TTSS-2-deficient Salmonella Typhimurium.

    Science.gov (United States)

    Felmy, Boas; Songhet, Pascal; Slack, Emma Marie Caroline; Müller, Andreas J; Kremer, Marcus; Van Maele, Laurye; Cayet, Delphine; Heikenwalder, Mathias; Sirard, Jean-Claude; Hardt, Wolf-Dietrich

    2013-01-01

    Infections, microbe sampling and occasional leakage of commensal microbiota and their products across the intestinal epithelial cell layer represent a permanent challenge to the intestinal immune system. The production of reactive oxygen species by NADPH oxidase is thought to be a key element of defense. Patients suffering from chronic granulomatous disease are deficient in one of the subunits of NADPH oxidase. They display a high incidence of Crohn's disease-like intestinal inflammation and are hyper-susceptible to infection with fungi and bacteria, including a 10-fold increased risk of Salmonellosis. It is not completely understood which steps of the infection process are affected by the NADPH oxidase deficiency. We employed a mouse model for Salmonella diarrhea to study how NADPH oxidase deficiency (Cybb (-/-)) affects microbe handling by the large intestinal mucosa. In this animal model, wild type S. Typhimurium causes pronounced enteropathy in wild type mice. In contrast, an avirulent S. Typhimurium mutant (S.Tm(avir); invGsseD), which lacks virulence factors boosting trans-epithelial penetration and growth in the lamina propria, cannot cause enteropathy in wild type mice. We found that Cybb (-/-) mice are efficiently infected by S.Tm(avir) and develop enteropathy by day 4 post infection. Cell depletion experiments and infections in Cybb (-/-) Myd88 (-/-) mice indicated that the S.Tm(avir)-inflicted disease in Cybb (-/-) mice hinges on CD11c(+)CX3CR1(+) monocytic phagocytes mediating colonization of the cecal lamina propria and on Myd88-dependent proinflammatory immune responses. Interestingly, in mixed bone marrow chimeras a partial reconstitution of Cybb-proficiency in the bone marrow derived compartment was sufficient to ameliorate disease severity. Our data indicate that NADPH oxidase expression is of key importance for restricting the growth of S.Tm(avir) in the mucosal lamina propria. This provides important insights into microbe handling by the large

  9. Enhanced FGF23 production in mice expressing PI3K-insensitive GSK3 is normalized by β-blocker treatment.

    Science.gov (United States)

    Fajol, Abul; Chen, Hong; Umbach, Anja T; Quarles, L Darryl; Lang, Florian; Föller, Michael

    2016-02-01

    Glycogen synthase kinase (GSK)-3 is a ubiquitously expressed kinase inhibited by insulin-dependent Akt/PKB/SGK. Mice expressing Akt/PKB/SGK-resistant GSK3α/GSK3β (gsk3(KI)) exhibit enhanced sympathetic nervous activity and phosphaturia with decreased bone density. Hormones participating in phosphate homeostasis include fibroblast growth factor (FGF)-23, a bone-derived hormone that inhibits 1,25-dihydroxyvitamin D3 (1,25(OH)2D3; calcitriol) formation and phosphate reabsorption in the kidney and counteracts vascular calcification and aging. FGF23 secretion is stimulated by the sympathetic nervous system. We studied the role of GSK3-controlled sympathetic activity in FGF23 production and phosphate metabolism. Serum FGF23, 1,25(OH)2D3, and urinary vanillylmandelic acid (VMA) were measured by ELISA, and serum and urinary phosphate and calcium were measured by photometry in gsk3(KI) and gsk3(WT) mice, before and after 1 wk of oral treatment with the β-blocker propranolol. Urinary VMA excretion, serum FGF23, and renal phosphate and calcium excretion were significantly higher, and serum 1,25(OH)2D3 and phosphate concentrations were lower in gsk3(KI) mice than in gsk3(WT) mice. Propranolol treatment decreased serum FGF23 and loss of renal calcium and phosphate and increased serum phosphate concentration in gsk3(KI) mice. We conclude that Akt/PKB/SGK-sensitive GSK3 inhibition participates in the regulation of FGF23 release, 1,25(OH)2D3 formation, and thus mineral metabolism, by controlling the activity of the sympathetic nervous system.

  10. CIDE-A gene expression is decreased in white adipose tissue of growth hormone receptor/binding protein gene disrupted mice and with high-fat feeding of normal mice.

    Science.gov (United States)

    Kelder, Bruce; Berryman, Darlene E; Clark, Ryan; Li, Aiyun; List, Edward O; Kopchick, John J

    2007-08-01

    Growth hormone's (GH) lipolytic activity in white adipose tissue (WAT) results in decreased body fat in giant GH transgenic mice and increased subcutaneous fat in dwarf growth hormone receptor/binding protein gene-disrupted mice (GHR -/-). We therefore hypothesized that GH action would affect expression of CIDE-A (cell-death-inducing DFF45-like effector-A), a protein found in white adipose tissue (WAT) and involved in lipid metabolism. CIDE-A RNA levels were determined in subcutaneous, retroperitoneal and epididymal adipose tissue isolated from wild-type and GHR -/- mice. The adipose tissue was also analyzed for adipocyte size. We determined that the lack of GH action has depot-specific effects on the levels of CIDE-A RNA and affected adipocyte cell size. CIDE-A expression is significantly reduced in GHR -/- subcutaneous fat compared to wild-type but is not altered in retroperitoneal or epididymal fat. Likewise, adipocytes are significantly enlarged in GHR -/- subcutaneous adipose tissue relative wild-type mice. A high-fat diet also influenced the level of CIDE-A RNA in mouse adipose tissue. The high-fat diet significantly reduced CIDE-A expression in wild-type subcutaneous fat but did not alter CIDE-A expression in subcutaneous fat of GHR -/- mice. The diet also reduced CIDE-A expression in wild-type retroperitoneal fat but the levels of CIDE-A in epididymal fat were unchanged. In contrast, the high-fat diet reduced CIDE-A expression in both retroperitoneal and epididymal fat of GHR -/- mice. These data demonstrate that CIDE-A levels are reduced in two different mouse models of obesity and this reduction may contribute to altered lipid metabolism.

  11. Hypoglycemic Effect of Crude Extracts of Leaves of Smallanthus sonchifolius ( Yacon )on Normal Mice%亚贡叶提取物对小鼠降血糖作用研究

    Institute of Scientific and Technical Information of China (English)

    潘红艳; 何凡; 窦德强; 董锋

    2012-01-01

    Objective: To investigate the hypoglycemic effect of crude extracts from Yacon leaves including water and ethanol extractions. Method: Choose the normal mice as model. The mice were treated orally with the extractions of dried yacon at dosage of 200mg/kg. Then, the blood glucose, fasting glucose, glucose, and sucrose tolerance were measured by FreeStyle blood glucose meter. Results: The mice's fasting glucose of water extraction group was significantly higher than the control and ethanol extract group after one hour. In the glucose tolerance experiment, blood glucose of the water extraction group was significantly lower than other groups after giving sucrose and glucose 30 minutes. Conclusion: The water extract of Yacon leaf can enhance glucose and sucrose tolerance in normal mice and help to prevent hypoglycemia caused by fasting.%目的:研究亚贡叶水取物和50%乙醇提取物对正常小鼠血糖及耐糖量的影响.方法:灌胃给予小鼠水提取物和乙醇提取物各200mg/kg,血糖仪测定其对正常小鼠的血糖、空腹血糖以及糖耐量的影响.结果:亚贡水提物组的小鼠空腹血糖在1h后血糖明显高于空白和乙醇提取物组;耐糖量实验中,给予蔗糖及葡萄糖30min后,水提物组的小鼠血糖明显低于其他组.结论:亚贡叶水提物能增强正常小鼠的耐糖量并能防止因禁食引起的低血糖现象.

  12. Congener-specific polychlorinated biphenyl patterns in eggs of aquatic birds from the lower Laguna Madre, Texas

    Science.gov (United States)

    Mora, Miguel A.

    1996-01-01

    Eggs from four aquatic bird species nesting in the Lower Laguna Madre, Texas, were collected to determine differences and similarities in the accumulation of congener-specific polychlorinated biphenyls (PCBs) and to evaluate PCB impacts on reproduction. Because of the different toxicities of PCB congeners, it is important to know which congeners contribute most to total PCBs. The predominant PCB congeners were 153, 138, 180, 110, 118, 187, and 92. Collectively, congeners 153, 138, and 180 accounted for 26 to 42% of total PCBs. Congener 153 was the most abundant in Caspian terns (Sterna caspia) and great blue herons (Ardea herodias) and congener 138 was the most abundant in snowy egrets (Egretta thula) and tricolored herons (Egretta tricolor). Principal component analysis indicated a predominance of higher chlorinated biphenyls in Caspian terns and great blue herons and lower chlorinated biphenyls in tricolored herons. Snowy egrets had a predominance of pentachlorobiphenyls. These results suggest that there are differences in PCB congener patterns in closely related species and that these differences are more likely associated with the species' diet rather than metabolism. Total PCBs were significantly greater (p Laguna Madre were below concentrations known to affect bird reproduction.

  13. Congener-specific polychlorinated biphenyl patterns in eggs of aquatic birds from the Lower Laguna Madre, Texas

    Energy Technology Data Exchange (ETDEWEB)

    Mora, M.A. [Texas A and M Univ., College Station, TX (United States)

    1996-06-01

    Eggs from four aquatic bird species nesting in the Lower Laguna Madre, Texas, were collected to determine differences and similarities in the accumulation of congener-specific polychlorinated biphenyls (PCBs) and to evaluate PCB impacts on reproduction. Because of the different toxicities of PCB congeners, it is important to know which congeners contribute most to total PCBs. The predominant PCB congeners were 153, 138, 180, 110, 118, 187, and 92. Collectively, congeners 153, 138, and 180 accounted for 26 to 42% of total PCBs. Congener 153 was the most abundant in Caspian terns (Sterna caspia) and great blue herons (Ardea herodias) and congener 138 was the most abundant in snowy egrets (Egretta thula) and tricolored herons (Egretta tricolor). Principal component analysis indicated a predominance of higher chlorinated biphenyls in Caspian terns and great blue herons and lower chlorinated biphenyls in tricolored herons. Snowy egrets had a predominance of pentachlorobiphenyls. These results suggest that there are differences in PCB congener patterns in closely related species and that these differences are more likely associated with the species` diet rather than metabolism. Total PCBs were significantly greater (p < 0.05) in Caspian terns than in the other species. Overall, PCBs in eggs of birds from the Lower Laguna Madre were below concentrations known to affect bird reproduction.

  14. Predicting sediment sorption coefficients for linear alkylbenzenesulfonate congeners from polyacrylate-water partition coefficients at different salinities.

    NARCIS (Netherlands)

    Rico Rico, A.; Droge, S.T.J.; Hermens, J.L.M.

    2010-01-01

    The effect of the molecular structure and the salinity on the sorption of the anionic surfactant linear alkylbenzenesulfonate (LAS) to marine sediment has been studied. The analysis of several individual LAS congeners in seawater and of one specific LAS congener at different dilutions of seawater wa

  15. Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

    Energy Technology Data Exchange (ETDEWEB)

    Sakaguchi, N.; Sakaguchi, S. (Stanford Univ. School of Medicine, CA (United States) Scripps Research Institute, La Jolla, CA (United States) PRESTO, JRDC, Institute of Phical and Chemical Research, Tsukuba, Ibaraki (Japan)); Miyai, K. (Univ. of California, San Diego, LA Jolla, CA (United States))

    1992-11-01

    Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.

  16. MMPIP, an mGluR7-selective negative allosteric modulator, alleviates pain and normalizes affective and cognitive behavior in neuropathic mice.

    Science.gov (United States)

    Palazzo, Enza; Romano, Rosaria; Luongo, Livio; Boccella, Serena; De Gregorio, Danilo; Giordano, Maria Elvira; Rossi, Francesca; Marabese, Ida; Scafuro, Maria Antonietta; de Novellis, Vito; Maione, Sabatino

    2015-06-01

    This study investigated the effects of a single administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridinyl-4-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), a negative allosteric modulator (NAM) of metabotropic glutamate receptor 7 (mGluR7), on pain and on affective and cognitive behavior in neuropathic mice. The activity of pyramidal neurons in the prelimbic cortex (PLC), which respond to stimulation of the basolateral amygdala (BLA) with either excitation or inhibition, was also investigated. The spared nerve injury (SNI) of the sciatic nerve induced, 14 days after surgery, thermal hyperalgesia and mechanical allodynia, reduced open-arm choice in the elevated plus-maze, increased time of immobility in the tail suspension, and increased digging and burying in the marble burying test. Cognitive performance was also significantly compromised in the SNI mice. Spared nerve injury induced phenotypic changes on pyramidal neurons of the PLC; excitatory responses increased, whereas inhibitory responses decreased after BLA stimulation. mGluR7 expression, mainly associated with vesicular glutamate transporter, increased in the hippocampus and decreased in the BLA, PLC, and dorsal raphe in SNI mice. MMPIP increased thermal and mechanical thresholds and open-arm choice. It reduced the immobility in the tail suspension test and the number of marbles buried and of digging events in the marble burying test. MMPIP also improved cognitive performance and restored the balance between excitatory and inhibitory responses of PLC neurons in SNI mice. 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one, XAP044, another selective mGluR7 NAM, reproduced the effects of MMPIP on thermal hyperalgesia, mechanical allodynia, tail suspension, and marble burying test. Altogether, these findings show that mGluR7 NAMs reduce pain responses and affective/cognitive impairments in neuropathic pain conditions.

  17. ANALYSIS OF CHIRAL PESTICIDES AND POLYCHLORINATED BIPHENYL CONGENERS IN ENVIRONMENTAL SAMPLES

    Science.gov (United States)

    Over 25 % of pesticides and other toxic organic pollutants are chiral, as are 19 of the 209 polychlorinated biphenyl (PCB) congeners; that is, they exist as two mirror image species called enantiomers (PCB enantiomers are called atropisomers). The enantiomers of a chiral compound...

  18. [Determination of seven toxaphene congeners in ginseng and milkvetch root by gas chromatography tandem mass spectrometry].

    Science.gov (United States)

    Tian, Shaoqiong; Mao, Xiuhong; Miao, Shui; Jia, Zhengwei; Wang, Ke; Ji, Shen

    2012-01-01

    A novel method for the determination of representative toxaphene congeners in traditional Chinese herbal medicines was developed. Ginseng and Milkvetch Root were selected as the samples and seven toxaphene congeners were selected as the monitoring objects. The samples were extracted by accelerated solvent extraction with cyclohexane-acetone (9:1, v/v), then cleaned-up by Florisil solid phase extraction with hexane as the eluent and the residues were detected by gas chromatography-electron ionization tandem mass spectrometry (GC-EI-MS/MS) in multiple reaction monitoring (MRM) mode. The performance was demonstrated by the analysis of Ginseng and Milkvetch Root samples spiked with toxaphene congeners at three concentration levels of 0.005, 0.01 and 0.1 mg/kg. The recoveries ranged from 72.4% to 105% with the relative standard deviations (RSDs) of 0.96%-10.4%. The limits of detection (LODs) were 0.2-1.7 microg/kg. This method is sensitive and efficient in the aspect of extraction, and can be applied to monitor the residue of toxaphene congeners in Ginseng and Milkvetch Root.

  19. DIFFERENTIAL EFFECTS OF TWO LOTS OF AROCLOR 1254R: CONGENER ANALYSIS AND NEUROCHEMICAL ENDPOINTS.

    Science.gov (United States)

    IntroductionPolychlorinated biphenyls (PCBs) are widely used in industry as heat transfer and dielectric fluids for transformers and capacitors1. PCBs were commercially produced as AroclorR mixtures in USA by the chlorination of biphenyl. Although all 209 congeners can be syn...

  20. Micelles versus Ribbons: How Congeners Drive the Self-Assembly of Acidic Sophorolipid Biosurfactants.

    Science.gov (United States)

    Dhasaiyan, Prabhu; Le Griel, Patrick; Roelants, Sophie; Redant, Emile; Van Bogaert, Inge N A; Prevost, Sylvain; Prasad, B L V; Baccile, Niki

    2017-03-17

    Sophorolipids (SLs), a class of microbially derived biosurfactants, are reported by different research groups to have different self-assembled structures (either micelles or giant ribbons) under the same conditions. Here we explore the reasons behind these contradictory results and attribute these differences to the role of specific congeners that are present in minute quantities. We show that a sample composed of a majority of oleic acid (C18:1) sophorolipid in the presence of only 0.5 % (or more) of congeners with stearic acid (C18:0) or linoleic acid (C18:2) results in the formation of micelles that are stable over long periods of time. Conversely, the presence of only 10 to 15 % of congeners with a stearic acid chain gives fibrillar structures instead of micelles. To study the mechanisms responsible, oleic acid SLs devoid of any other congeners were prepared. Very interestingly, this sample can self-assemble into either micelles or fibers depending on minute modifications to the self-assembly conditions. The findings are supported by light scattering, small-angle X-ray scattering, transmission electron microscopy under cryogenic conditions, high-pressure liquid chromatography, and NMR spectroscopy.

  1. NADPH oxidase deficient mice develop colitis and bacteremia upon infection with normally avirulent, TTSS-1- and TTSS-2-deficient Salmonella Typhimurium.

    Directory of Open Access Journals (Sweden)

    Boas Felmy

    Full Text Available Infections, microbe sampling and occasional leakage of commensal microbiota and their products across the intestinal epithelial cell layer represent a permanent challenge to the intestinal immune system. The production of reactive oxygen species by NADPH oxidase is thought to be a key element of defense. Patients suffering from chronic granulomatous disease are deficient in one of the subunits of NADPH oxidase. They display a high incidence of Crohn's disease-like intestinal inflammation and are hyper-susceptible to infection with fungi and bacteria, including a 10-fold increased risk of Salmonellosis. It is not completely understood which steps of the infection process are affected by the NADPH oxidase deficiency. We employed a mouse model for Salmonella diarrhea to study how NADPH oxidase deficiency (Cybb (-/- affects microbe handling by the large intestinal mucosa. In this animal model, wild type S. Typhimurium causes pronounced enteropathy in wild type mice. In contrast, an avirulent S. Typhimurium mutant (S.Tm(avir; invGsseD, which lacks virulence factors boosting trans-epithelial penetration and growth in the lamina propria, cannot cause enteropathy in wild type mice. We found that Cybb (-/- mice are efficiently infected by S.Tm(avir and develop enteropathy by day 4 post infection. Cell depletion experiments and infections in Cybb (-/- Myd88 (-/- mice indicated that the S.Tm(avir-inflicted disease in Cybb (-/- mice hinges on CD11c(+CX3CR1(+ monocytic phagocytes mediating colonization of the cecal lamina propria and on Myd88-dependent proinflammatory immune responses. Interestingly, in mixed bone marrow chimeras a partial reconstitution of Cybb-proficiency in the bone marrow derived compartment was sufficient to ameliorate disease severity. Our data indicate that NADPH oxidase expression is of key importance for restricting the growth of S.Tm(avir in the mucosal lamina propria. This provides important insights into microbe handling by the

  2. [Effect of maternal genotype on the rate of preimplantation development in mice].

    Science.gov (United States)

    Osipov, V V; Vakhrusheva, M P

    1981-01-01

    The genetic control of the rate of preimplantation development was studied in the mouse embryos. The number of cells in the embryo and the percentage of embryos at the blastocyst stage were determined on the 3.5 day of pregnancy. The experiments were carried out with CBA, A/He, C57Bl/Mib mice and mice homozygous by the mutant genes white (Miwh), fidget (fi) and ocular retardation (or), congenic with the inbred C57Bl/Mib mice. Contrasting differences were found between C57Bl/Mib and fi/fi mice. The rate of development of the morphologically normal C57Bl/Mib and fi/fi and F1 embryo was shown to depend on the maternal genotype, rather than on the paternal one. The effect of maternal genotype of the rate of preimplantation development was related to differences in the time of beginning of the cleavage. The rate of cleavage is similar for the C57Bl/Mib, fi/fi and F1 embryos.

  3. Congener specificity in the accumulation of dioxins and dioxin-like compounds in zucchini plants grown hydroponically.

    Science.gov (United States)

    Inui, Hideyuki; Wakai, Taketo; Gion, Keiko; Yamazaki, Kiyoshi; Kim, Yun-Seok; Eun, Heesoo

    2011-01-01

    Zucchini cultivars Cucurbita pepo subsp. ovifera cv. Patty Green and subsp. pepo cv. Gold Rush were cultivated hydroponically in a nutrient solution supplemented with a mixture of dioxins and dioxin-like compounds. Patty Green and Gold Rush showed low and high accumulation of these compounds in the aerial parts respectively. In both cultivars, the accumulation of each congener negatively depended on its hydrophobicity. This suggests that desorption and solubilization were partly responsible for congener specificity of accumulation, since this was not found in soil experiments. In contrast, no clear difference in accumulation in the roots was observed between the cultivars, whereas the translocation factors, which are indicators of efficient translocation from the roots to the aerial parts, differed among the congeners hydrophobicity-dependently. There were positive correlations between accumulation in the roots and the hydrophobicity of the polychlorinated biphenyl congeners in both cultivars. These results indicate that translocation was also partly responsible for the congener specificity and accumulation concentrations.

  4. Elimination Rates of Dioxin Congeners in Former Chlorophenol Workers from Midland, Michigan

    Science.gov (United States)

    Collins, James J.; Bodner, Kenneth M.; Wilken, Michael; Bodnar, Catherine M.

    2012-01-01

    Background: Exposure reconstructions and risk assessments for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxins rely on estimates of elimination rates. Limited data are available on elimination rates for congeners other than TCDD. Objectives: We estimated apparent elimination rates using a simple first-order one-compartment model for selected dioxin congeners based on repeated blood sampling in a previously studied population. Methods: Blood samples collected from 56 former chlorophenol workers in 2004–2005 and again in 2010 were analyzed for dioxin congeners. We calculated the apparent elimination half-life in each individual for each dioxin congener and examined factors potentially influencing elimination rates and the impact of estimated ongoing background exposures on rate estimates. Results: Mean concentrations of all dioxin congeners in the sampled participants declined between sampling times. Median apparent half-lives of elimination based on changes in estimated mass in the body were generally consistent with previous estimates and ranged from 6.8 years (1,2,3,7,8,9-hexachlorodibenzo-p-dioxin) to 11.6 years (pentachlorodibenzo-p-dioxin), with a composite half-life of 9.3 years for TCDD toxic equivalents. None of the factors examined, including age, smoking status, body mass index or change in body mass index, initial measured concentration, or chloracne diagnosis, was consistently associated with the estimated elimination rates in this population. Inclusion of plausible estimates of ongoing background exposures decreased apparent half-lives by approximately 10%. Available concentration-dependent toxicokinetic models for TCDD underpredicted observed elimination rates for concentrations dioxin compounds. PMID:23063871

  5. Educating Normal Breast Mucosa to Prevent Breast Cancer

    Science.gov (United States)

    2014-05-01

    Virus Control While Maintaining Efficacy in an Engineered Cancer Vaccine Kevin D Pavelko1, Michael P Bell1, Lavakumar Karyampudi1, Michael J Hansen1... Germany ). Congenic CD45.1 mice received 1 × 107 purified CD8+ T cells labeled with CFSE by intravenous transfer and were intraperitoneally infected...features. Clin Cancer Res 17: 888–895. 33. Chiu, CY, Greninger, AL, Kanada, K, Kwok, T, Fischer , KF, Runckel, C et al. (2008). Identification of

  6. Mice lacking NMDA receptors in parvalbumin neurons display normal depression-related behavior and response to antidepressant action of NMDAR antagonists.

    Directory of Open Access Journals (Sweden)

    Laura Pozzi

    Full Text Available The underlying circuit imbalance in major depression remains unknown and current therapies remain inadequate for a large group of patients. Discovery of the rapid antidepressant effects of ketamine--an NMDA receptor (NMDAR antagonist--has linked the glutamatergic system to depression. Interestingly, dysfunction in the inhibitory GABAergic system has also been proposed to underlie depression and deficits linked to GABAergic neurons have been found with human imaging and in post-mortem material from depressed patients. Parvalbumin-expressing (PV GABAergic interneurons regulate local circuit function through perisomatic inhibition and their activity is NMDAR-dependent, providing a possible link between NMDAR and the inhibitory system in the antidepressant effect of ketamine. We have therefore investigated the role of the NMDAR-dependent activity of PV interneurons for the development of depression-like behavior as well as for the response to rapid antidepressant effects of NMDAR antagonists. We used mutant mice lacking NMDA neurotransmission specifically in PV neurons (PV-Cre+/NR1f/f and analyzed depression-like behavior and anhedonia. To study the acute and sustained effects of a single NMDAR antagonist administration, we established a behavioral paradigm of repeated exposure to forced swimming test (FST. We did not observe altered behavioral responses in the repeated FST or in a sucrose preference test in mutant mice. In addition, the behavioral response to administration of NMDAR antagonists was not significantly altered in mutant PV-Cre+/NR1f/f mice. Our results show that NMDA-dependent neurotransmission in PV neurons is not necessary to regulate depression-like behaviors, and in addition that NMDARs on PV neurons are not a direct target for the NMDAR-induced antidepressant effects of ketamine and MK801.

  7. Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-β levels in male mice.

    Science.gov (United States)

    Savignac, Helene M; Couch, Yvonne; Stratford, Michael; Bannerman, David M; Tzortzis, George; Anthony, Daniel C; Burnet, Philip W J

    2016-02-01

    The manipulation of the enteric microbiota with specific prebiotics and probiotics, has been shown to reduce the host's inflammatory response, alter brain chemistry, and modulate anxiety behaviour in both rodents and humans. However, the neuro-immune and behavioural effects of prebiotics on sickness behaviour have not been explored. Here, adult male CD1 mice were fed with a specific mix of non-digestible galacto-oligosaccharides (Bimuno®, BGOS) for 3 weeks, before receiving a single injection of lipopolysaccharide (LPS), which induces sickness behaviour and anxiety. Locomotor and marble burying activities were assessed 4h after LPS injection, and after 24h, anxiety in the light-dark box was assessed. Cytokine expression, and key components of the serotonergic (5-Hydroxytryptamine, 5-HT) and glutamatergic system were evaluated in the frontal cortex to determine the impact of BGOS administration at a molecular level. BGOS-fed mice were less anxious in the light-dark box compared to controls 24h after the LPS injection. Elevated cortical IL-1β concentrations in control mice 28 h after LPS were not observed in BGOS-fed animals. This significant BGOS×LPS interaction was also observed for 5HT2A receptors, but not for 5HT1A receptors, 5HT, 5HIAA, NMDA receptor subunits, or other cytokines. The intake of BGOS did not influence LPS-mediated reductions in marble burying behaviour, and its effect on locomotor activity was equivocal. Together, our data show that the prebiotic BGOS has an anxiolytic effect, which may be related to the modulation of cortical IL-1β and 5-HT2A receptor expression. Our data suggest a potential role for prebiotics in the treatment of neuropsychiatric disorders where anxiety and neuroinflammation are prominent clinical features.

  8. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

    OpenAIRE

    Busby, Ellen R.; Sherwood, Nancy M.

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that...

  9. Roles of estrogen and progesterone in normal mammary gland development insights from progesterone receptor null mutant mice and in situ localization of receptor.

    Science.gov (United States)

    Shyamala, G

    1997-01-01

    In contrast to most other organs, the development of normal mammary glands occurs mostly in the postnatal state and in a discontinuous fashion. In all species, the glands are composed of various cell types, and it is the epithelium, embedded in the fatty stroma (commonly known as the "fat pad"), that is targeted for proliferation and differentiation. Hormones, in particular the female sex steroids estrogen and progesterone, are absolutely essential for the proliferation of mammary epithelial cell. However, despite intensive efforts by many laboratories spanning nearly 4 decades, at present, the precise role of these steroids and their relative importance in mammary development remains unclear. This article reviews the general features and the effects of estrogen and progesterone on normal mammary gland development, followed by a discussion of our recent studies, which emphasize the primary importance of progesterone and progesterone receptor for the normal mammary epithelial cell proliferation and differentiation. (c) 1997, Elsevier Science Inc. (Trends Endocrinol Metab 1997;8:34-39).

  10. Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes

    Science.gov (United States)

    Sarahan, Kari A.; Fisler, Janis S.

    2011-01-01

    We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions. PMID:21730028

  11. Four out of eight genes in a mouse chromosome 7 congenic donor region are candidate obesity genes.

    Science.gov (United States)

    Sarahan, Kari A; Fisler, Janis S; Warden, Craig H

    2011-09-22

    We previously identified a region of mouse chromosome 7 that influences body fat mass in F2 littermates of congenic × background intercrosses. Current analyses revealed that alleles in the donor region of the subcongenic B6.C-D7Mit318 (318) promoted a twofold increase in adiposity in homozygous lines of 318 compared with background C57BL/6ByJ (B6By) mice. Parent-of-origin effects were discounted through cross-fostering studies and an F1 reciprocal cross. Mapping of the donor region revealed that it has a maximal size of 2.8 Mb (minimum 1.8 Mb) and contains a maximum of eight protein coding genes. Quantitative PCR in whole brain, liver, and gonadal white adipose tissue (GWAT) revealed differential expression between genotypes for three genes in females and two genes in males. Alpha-2,8-sialyltransferase 8B (St8sia2) showed reduced 318 mRNA levels in brain for females and males and in GWAT for females only. Both sexes of 318 mice had reduced Repulsive guidance molecule-a (Rgma) expression in GWAT. In brain, Family with sequence similarity 174 member b (Fam174b) had increased expression in 318 females, whereas Chromodomain helicase DNA binding protein 2 (Chd2-2) had reduced expression in 318 males. No donor region genes were differentially expressed in liver. Sequence analysis of coding exons for all genes in the 318 donor region revealed only one single nucleotide polymorphism that produced a nonsynonymous missense mutation, Gln7Pro, in Fam174b. Our findings highlight the difficulty of using expression and sequence to identify quantitative trait genes underlying obesity even in small genomic regions.

  12. H-11-linked gene has a parallel effect on Leishmania major and L. donovani infections in mice

    Energy Technology Data Exchange (ETDEWEB)

    Blackwell, J.M.; Hale, C.; Roberts, M.B.; Ulczak, O.M.; Liew, F.Y.; Howard, J.G.

    1985-01-01

    The courses of visceral infection following intravenous injection of Leishmania donovani amastigotes, or lesion growth following subcutaneous injection of L. major promastigotes, were examined in B10.129(10M) (H-2b, H-11b) mice and compared with disease profiles observed in congenic C57BL/10ScSn(= B10) (H-2b, H-11a) and B10.D2/n (H-2d, H-11a) mice, and in BALB/mice. Possession of alternative alleles at H-11 and closely linked loci transformed the normal curing/healing phenotype of B10 mice into a characteristically different noncuring/nonhealing phenotype affecting both visceral and subcutaneous infections in B10.129(10M) mice. In reciprocal radiation bone marrow chimeras made between the congenic B10 and B10.129(10M) strains, both cure and noncure phenotypes were transferable with the donor hematopoietic system. Although it was possible to demonstrate transfer of suppression with T-enriched spleen cells from day 61 L. donovani-infected B10.129(10M) donor mice into 550 rad syngeneic recipients, the pretreatment of mice with sublethal irradiation did not, as in the earlier studies of Scl-controlled L. major nonhealing or H-2-controlled L. donovani noncure phenotypes, have a clear or consistent prophylactic effect. Together with the progressive disease profile observed even for L. donovani at low parasite doses this suggests that, despite their ability to develop initial delayed-type hypersensitivity reactions to parasite antigen early in L. major infection, B10.129(10M) mice possess some inherent defect in ability to mount a cell-mediated response effective at the level of macrophage neishmanial activity in vivo even when suppressor T cells are not generated. Elucidation of this characteristically different noncuring/nonhealing phenotye may provide important insight into common events involved in the development of the cell-mediated immune response to both visceral and subcutaneous forms of leishmaniasis.

  13. Normal X-inactivation mosaicism in corneas of heterozygous FlnaDilp2/+ female mice--a model of human Filamin A (FLNA diseases

    Directory of Open Access Journals (Sweden)

    Douvaras Panagiotis

    2012-02-01

    Full Text Available Abstract Background Some abnormalities of mouse corneal epithelial maintenance can be identified by the atypical mosaic patterns they produce in X-chromosome inactivation mosaics and chimeras. Human FLNA/+ females, heterozygous for X-linked, filamin A gene (FLNA mutations, display a range of disorders and X-inactivation mosaicism is sometimes quantitatively unbalanced. FlnaDilp2/+ mice, heterozygous for an X-linked filamin A (Flna nonsense mutation have variable eye, skeletal and other abnormalities, but X-inactivation mosaicism has not been investigated. The aim of this study was to determine whether X-inactivation mosaicism in the corneal epithelia of FlnaDilp2/+ mice was affected in any way that might predict abnormal corneal epithelial maintenance. Results X-chromosome inactivation mosaicism was studied in the corneal epithelium and a control tissue (liver of FlnaDilp2/+ and wild-type (WT female X-inactivation mosaics, hemizygous for the X-linked, LacZ reporter H253 transgene, using β-galactosidase histochemical staining. The corneal epithelia of FlnaDilp2/+ and WT X-inactivation mosaics showed similar radial, striped patterns, implying epithelial cell movement was not disrupted in FlnaDilp2/+ corneas. Corrected stripe numbers declined with age overall (but not significantly for either genotype individually, consistent with previous reports suggesting an age-related reduction in stem cell function. Corrected stripe numbers were not reduced in FlnaDilp2/+ compared with WT X-inactivation mosaics and mosaicism was not significantly more unbalanced in the corneal epithelia or livers of FlnaDilp2/+ than wild-type Flna+/+ X-inactivation mosaics. Conclusions Mosaic analysis identified no major effect of the mouse FlnaDilp2 mutation on corneal epithelial maintenance or the balance of X-inactivation mosaicism in the corneal epithelium or liver.

  14. The 18 kDa translocator protein (peripheral benzodiazepine receptor) expression in the bone of normal, osteoprotegerin or low calcium diet treated mice.

    Science.gov (United States)

    Kam, Winnie Wai-Ying; Meikle, Steven R; Zhou, Hong; Zheng, Yu; Blair, Julie M; Seibel, Marcus; Dunstan, Colin R; Banati, Richard B

    2012-01-01

    The presence of the translocator protein (TSPO), previously named as the mitochondrial or peripheral benzodiazepine receptor, in bone cells was studied in vitro and in situ using RT-qPCR, and receptor autoradiography using the selective TSPO ligand PK11195.In vitro, the TSPO is highly expressed in osteoblastic and osteoclastic cells.In situ, constitutive expression of TSPO is found in bone marrow and trabecular bone, e.g., spongiosa. Mice with a reduction of bone turnover induced by a 4-day treatment of osteoprotegerin reduces [(3)H]PK11195 binding in the spongiosa (320±128 Bq x mg(-1), 499±106 Bq x mg(-1) in saline-treated controls). In contrast, mice with an increase in bone turnover caused by a 4-day low calcium diet increases [(3)H]PK11195 binding in the spongiosa (615±90 Bq x mg(-1)). Further, our study includes technical feasibility data on [(18)F]fluoride microPET imaging of rodent bone with altered turnover. Despite [(18)F]fluoride having high uptake, the in vivo signal differences were small. Using a phantom model, we describe the spillover effect and partial volume loss that affect the quantitative microPET imaging of the small bone structures in experimental mouse models. In summary, we demonstrate the expression of TSPO in small rodent bone tissues, including osteoblasts and osteoclasts. A trend increase in TSPO expression was observed in the spongiosa from low to high bone turnover conditions. However, despite the potential utility of TSPO expression as an in vivo biomarker of bone turnover in experimental rodent models, our small animal PET imaging data using [(18)F]fluoride show that even under the condition of a good biological signal-to-noise ratio and high tracer uptake, the currently achievable instrument sensitivity and spatial resolution is unlikely to be sufficient to detect subtle differences in small structures, such as mouse bone.

  15. The 18 kDa translocator protein (peripheral benzodiazepine receptor expression in the bone of normal, osteoprotegerin or low calcium diet treated mice.

    Directory of Open Access Journals (Sweden)

    Winnie Wai-Ying Kam

    Full Text Available The presence of the translocator protein (TSPO, previously named as the mitochondrial or peripheral benzodiazepine receptor, in bone cells was studied in vitro and in situ using RT-qPCR, and receptor autoradiography using the selective TSPO ligand PK11195.In vitro, the TSPO is highly expressed in osteoblastic and osteoclastic cells.In situ, constitutive expression of TSPO is found in bone marrow and trabecular bone, e.g., spongiosa. Mice with a reduction of bone turnover induced by a 4-day treatment of osteoprotegerin reduces [(3H]PK11195 binding in the spongiosa (320±128 Bq x mg(-1, 499±106 Bq x mg(-1 in saline-treated controls. In contrast, mice with an increase in bone turnover caused by a 4-day low calcium diet increases [(3H]PK11195 binding in the spongiosa (615±90 Bq x mg(-1. Further, our study includes technical feasibility data on [(18F]fluoride microPET imaging of rodent bone with altered turnover. Despite [(18F]fluoride having high uptake, the in vivo signal differences were small. Using a phantom model, we describe the spillover effect and partial volume loss that affect the quantitative microPET imaging of the small bone structures in experimental mouse models. In summary, we demonstrate the expression of TSPO in small rodent bone tissues, including osteoblasts and osteoclasts. A trend increase in TSPO expression was observed in the spongiosa from low to high bone turnover conditions. However, despite the potential utility of TSPO expression as an in vivo biomarker of bone turnover in experimental rodent models, our small animal PET imaging data using [(18F]fluoride show that even under the condition of a good biological signal-to-noise ratio and high tracer uptake, the currently achievable instrument sensitivity and spatial resolution is unlikely to be sufficient to detect subtle differences in small structures, such as mouse bone.

  16. Mapping of a chromosome 12 region associated with airway hyperresponsiveness in a recombinant congenic mouse strain and selection of potential candidate genes by expression and sequence variation analyses.

    Directory of Open Access Journals (Sweden)

    Cynthia Kanagaratham

    Full Text Available In a previous study we determined that BcA86 mice, a strain belonging to a panel of AcB/BcA recombinant congenic strains, have an airway responsiveness phenotype resembling mice from the airway hyperresponsive A/J strain. The majority of the BcA86 genome is however from the hyporesponsive C57BL/6J strain. The aim of this study was to identify candidate regions and genes associated with airway hyperresponsiveness (AHR by quantitative trait locus (QTL analysis using the BcA86 strain. Airway responsiveness of 205 F2 mice generated from backcrossing BcA86 strain to C57BL/6J strain was measured and used for QTL analysis to identify genomic regions in linkage with AHR. Consomic mice for the QTL containing chromosomes were phenotyped to study the contribution of each chromosome to lung responsiveness. Candidate genes within the QTL were selected based on expression differences in mRNA from whole lungs, and the presence of coding non-synonymous mutations that were predicted to have a functional effect by amino acid substitution prediction tools. One QTL for AHR was identified on Chromosome 12 with its 95% confidence interval ranging from 54.6 to 82.6 Mbp and a maximum LOD score of 5.11 (p = 3.68 × 10(-3. We confirmed that the genotype of mouse Chromosome 12 is an important determinant of lung responsiveness using a Chromosome 12 substitution strain. Mice with an A/J Chromosome 12 on a C57BL/6J background have an AHR phenotype similar to hyperresponsive strains A/J and BcA86. Within the QTL, genes with deleterious coding variants, such as Foxa1, and genes with expression differences, such as Mettl21d and Snapc1, were selected as possible candidates for the AHR phenotype. Overall, through QTL analysis of a recombinant congenic strain, microarray analysis and coding variant analysis we identified Chromosome 12 and three potential candidate genes to be in linkage with airway responsiveness.

  17. Induction of heme oxygenase-1 by whisky congeners in human endothelial cells.

    Science.gov (United States)

    Suzuki, Keiko; Nemoto, Asuka; Tanaka, Izumi; Koshimizu, Seiichi; Suwa, Yoshihide; Ishihara, Hiroshi

    2010-08-01

    It is expected that the production of the cytoprotective heme oxygenase-1 (HO-1) protein in endothelial cells would reduce severity of vascular injuries, while phenolic compounds are known to induce HO-1 mRNA and protein in various cells. We investigated the activation of HO-1 by whisky, which contains various phenolic substances. The congeners of whisky stored from 4 to 18 y in oak barrels were shown to induce an increase of HO-1 protein in human umbilical vein endothelial cells, while those of freshly distilled whisky spirit exhibited no activity. To determine the compounds with potent HO-1-inducing activity among the whisky congeners, several chemicals that had been reported to exist in whisky or oak barrels were screened, and coniferyl aldehyde and sinapyl aldehyde showed the activity. Thus, compounds that emerged in whisky during barrel storage induced cytoprotective protein, HO-1, in human endothelial cells.

  18. Accumulation and depletion of polychlorinated biphenyl (PCB) congeners in the housefly (musca domestica, L. )

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, L.G. (Univ. of Illinois, Urbana (United States)); Storr-Hansen, E. (National Environmental Research Inst., Soeborg (Denmark))

    1992-01-01

    Polychlorinated biphenyl (PCB) residues in food chains and in the environment are dynamic complex mixtures and there is considerable interest in the disposition as well as toxicities of individual congeners. The persistence and biological activities of PCBs are intimately associated with microsomal monooxygenases. The house fly, Musca domestica (L.), has long been a standard organism for studies of pesticide toxicology and has an active and well-defined microsomal monooxygenase system. These oxidases in the fly can be induced by PCBs. It was considered of interest to provide data which may indicate whether or not the relatively large and mobile biomass of insects in general may play a role in the global disposition of PCBs. It was also of interest to determine if the house fly could serve as a model for determining the relative accumulation, elimination, and toxicities of individual PCB congeners.

  19. Differences of CD4+CD25+ regulatory T cells between food allergy mice and normal mice%食物过敏与正常小鼠CD4+CD25+调节性T细胞的差异性研究

    Institute of Scientific and Technical Information of China (English)

    程茜; 陈玉梅

    2013-01-01

    Objective:To compare the quantities and functions of CD4+CD25+ regulatory T(Treg)cells between food allergy mice model and normal mice model. Methods: SPF Balb/c female mice of 4-6 weeks on egg-free diet were randomly divided into ovalbumin (OVA) group(n=8) and normal control group(n=8). Quantitative changes of CD4+CD25+ Treg cells in the spleen mononuclear cell suspension were analyzed by flow cytometry. Levels of serum interleukin-lO(IL-lO) and transforming growth factor-β1(TGF-βl) in OVA mice and normal control mice were detected by enzyme-linked immunosorbent assay (ELISA). Results: Percentage of CD4+ CD25+ Treg cells in OVA group was lower than that in normal control group (P<0.05 ), and percentage of forkhead transcription factor3+(Foxp3 + )CD4+CD25 + Treg cells in OVA group was significantly lower in OVA group than in normal control group(P<0.01). Levels of IL-10 and TGF-β1 were lower in OVA group than in normal control group(P<0.05)(P<0.01). Conclusions:There are differences in quantities and functions of Treg cells between food allergy and normal mice.%目的:比较食物过敏(food allergy,FA)小鼠与正常小鼠模型CD4+CD25+调节性T(regulatory T,Treg)细胞数量及功能差异.方法:4~6周龄SPF级无鸡蛋喂养Balb/c雌鼠随机分为2组,每组8只.分别为卵清蛋白(ovalbumin,OVA)致敏组和正常对照组.采用流式细胞术分析其脾脏单个核细胞悬液中CD4+CD25+ Treg细胞的数量变化;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测OVA致敏组与正常对照组血清白介素10(interleukin-10,IL-10)和转化生长因子-β1 (transforming growth factor-β1,TGF-β1)水平.结果:OVA组CD4+CD25+T淋巴细胞的百分比低于正常对照组(P<0.05),并且叉状头转录因子3阳性(forkhead transcription factor3+,Foxp3+)CD4+CD25+Treg细胞的百分比显著低于正常对照组(P<0.01);OVA组IL-10低于正常对照组(P<0.05),TGF-β1水平显著低于正常对照组(P<0.01).结论:FA

  20. Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism

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    Kaisa M. Kettunen

    2016-05-01

    Full Text Available Mulibrey nanism (MUL is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37−/− model for MUL. Trim37−/− mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37−/− mice as compared with wild-type. Both male and female Trim37−/− mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37−/− mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37−/− mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37−/− mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37−/− mice. The most consistently seen phenotypes in Trim37−/− mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37−/− mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis.

  1. Polychlorinated biphenyls and breast cancer: A congener-specific meta-analysis.

    Science.gov (United States)

    Leng, Ling; Li, Jing; Luo, Xiu-mei; Kim, Jun-young; Li, Yi-meng; Guo, Xue-mei; Chen, Xi; Yang, Qiao-yun; Li, Guang; Tang, Nai-jun

    2016-03-01

    The incidence of breast cancer is related to various risk factors, especially that the environmental and lifestyle factors account for major contribution at the rate of 70% to 95% over all. However, there still remains some controversy over the epidemiological evidence regarding the effects of environmental carcinogens on the risk of breast cancer. We conducted a quantitative meta-analysis aiming at full evaluation of the effects of polychlorinated biphenyls (PCBs) on breast cancer in a congener-specific fashion. Four online literature databases were systematically searched before 1st January 2015, for studies stating correlation between PCB congeners and breast cancer. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies that were included in our analysis. Sixteen studies were included in our final meta-analysis after screening based on the priori inclusion criteria. Nine PCB congeners were reported by more than two studies and they were presented in detail. The pooled Odds Ratios (ORs) showed a significant increase in the risk of breast cancer in individuals with higher plasma/fat levels of PCB 99 (OR: 1.36; 95% CI: 1.02 to 1.80), PCB 183 (OR: 1.56; 95% CI: 1.25 to 1.95) and PCB 187 (OR: 1.18; 95% CI: 1.01 to 1.39). Besides, the outcomes did not support a relationship between dioxin-like PCB congeners and the risk of breast cancer. The results of our meta-analysis imply that PCB 99, PCB 183 and PCB 187 would increase the risk of breast cancer. The mechanism of this increased risk may be by the induction of the CYP2B family in cytochrome P450 enzymes.

  2. Synthesis and antiprotozoal properties of pentamidine congeners bearing the benzofuran motif.

    Science.gov (United States)

    Bakunov, Stanislav A; Bakunova, Svetlana M; Bridges, Arlene S; Wenzler, Tanja; Barszcz, Todd; Werbovetz, Karl A; Brun, Reto; Tidwell, Richard R

    2009-09-24

    Forty-eight cationically substituted pentamidine congeners possessing benzofuran rings were synthesized by a copper mediated heteroannulation of substituted o-iodophenols with phenyl acetylenes. Activities of compounds 1-48 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cytotoxicities for mammalian cells were influenced by the nature of cationic substituents, placement of the benzofuran fragment, and the length of the carbon linker between aromatic moieties. Several dications exhibited superior antiplasmodial and antileishmanial potencies compared to pentamidine.

  3. Uptake of 111In-labeled fully human monoclonal antibody TSP-A18 reflects transferrin receptor expression in normal organs and tissues of mice.

    Science.gov (United States)

    Sugyo, Aya; Tsuji, Atsushi B; Sudo, Hitomi; Nomura, Fumiko; Satoh, Hirokazu; Koizumi, Mitsuru; Kurosawa, Gene; Kurosawa, Yoshikazu; Saga, Tsuneo

    2017-03-01

    Transferrin receptor (TfR) is an attractive molecule for targeted therapy of cancer. Various TfR-targeted therapeutic agents such as anti-TfR antibodies conjugated with anticancer agents have been developed. An antibody that recognizes both human and murine TfR is needed to predict the toxicity of antibody-based agents before clinical trials, there is no such antibody to date. In this study, a new fully human monoclonal antibody TSP-A18 that recognizes both human and murine TfR was developed and the correlation analysis of the radiolabeled antibody uptake and TfR expression in two murine strains was conducted. TSP-A18 was selected using extracellular portions of human and murine TfR from a human antibody library. The cross-reactivity of TSP-A18 with human and murine cells was confirmed by flow cytometry. Cell binding and competitive inhibition assays with [111In]TSP-A18 showed that TSP-A18 bound highly to TfR-expressing MIAPaCa-2 cells with high affinity. Biodistribution studies of [111In]TSP-A18 and [67Ga]citrate (a transferrin-mediated imaging probe) were conducted in C57BL/6J and BALB/c-nu/nu mice. [111In]TSP-A18 was accumulated highly in the spleen and bone containing marrow component of both strains, whereas high [67Ga]citrate uptake was only observed in bone containing marrow component and not in the spleen. Western blotting indicated the spleen showed the strongest TfR expression compared with other organs in both strains. There was significant correlation between [111In]TSP-A18 uptake and TfR protein expression in both strains, whereas there was significant correlation of [67Ga]citrate uptake with TfR expression only in C57BL/6J. These findings suggest that the difference in TfR expression between murine strains should be carefully considered when testing for the toxicity of anti-TfR antibody in mice and the uptake of anti-TfR antibody could reflect tissue TfR expression more accurately compared with that of transferrin-mediated imaging probe such as [67Ga]citrate.

  4. Effects of the cannabinoid 1 receptor peptide ligands hemopressin, (m)RVD-hemopressin(α) and (m)VD-hemopressin(α) on memory in novel object and object location recognition tasks in normal young and Aβ1-42-treated mice.

    Science.gov (United States)

    Zhang, Rui-San; He, Zhen; Jin, Wei-Dong; Wang, Rui

    2016-10-01

    The cannabinoid system plays an important role in memory processes, many studies have indicated that cannabinoid receptor ligands have ability to modulate memory in rodents. A nonapeptide hemopressin (Hp) derived from rat brain, acts as a peptide antagonist or selective inverse peptide agonist of cannabinoid 1 (CB1) receptor. N-terminally extended forms of Hp isolated from mouse brain, (m)RVD-hemopressin(α) (RVD) and (m)VD-hemopressin(α) (VD) also bind CB1 receptor, however, as peptide agonists. Here, we investigated the roles of Hp, RVD, and VD on memory in mice using novel object recognition (NOR) and object location recognition (OLR) tasks. In normal young mice, intracerebroventricular (i.c.v.) infusion of Hp before training not only improved memory formation, but also prolonged memory retention in the tasks, these effects could be inhibited by RVD or VD at the same dose and intraperitoneal (i.p.) injection of a small molecule agonist of CB1 receptor WIN55, 212-2 15min before administration of Hp inhibited the memory-improving effect of Hp. In addition, under the same experimental conditions, i.c.v. RVD or VD displayed memory-impairing effects, which could be prevented by Hp (i.c.v.) or AM251 (i.p.), a small molecule antagonist of CB1 receptor. Infusion of amyloid-β (1-42) (Aβ1-42) 14days before training resulted in impairment of memory in mice which could be used as animal model of Alzheimer's disease (AD). In these mice, RVD or VD (i.c.v.) reversed the memory impairment induced by Aβ1-42, and the effects of RVD and VD could be suppressed by Hp (i.c.v.) or AM251 (2mg/kg, i.p.). Separate administration of Hp had no effect in Aβ1-42-treated mice. The above results suggested that Hp, RVD and VD, as CB1 receptor peptide ligands, may be potential drugs to treatment of the memory deficit-involving disease, just as AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Occurrence and congeners specific of polychlorinated biphenyls in agricultural soils from Southern Jiangsu, China

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian-ying; QIU Li-min; HE Jia; LIAO Yuan; LUO Yong-ming

    2007-01-01

    A total of 198 agricultural soil samples were collected from Zhangjiagang and Changshu in Southern Jiangsu for analysis of 13 polychlorinated biphenyls(PCBs)in order to assess the levels of pollution,sources,area distribution,and potential risk for the environment.All methods were rigorously tested and an adequate quality control was ensured.Only one site had no PCBs residues,and the highest total PCBs concentration in the surface soils was 32.83 ng/g.The average concentration in all the soil samples was 4.13ng/g.signaling low-level pollution.Tetra-,penta-,and hexa-chlorinated biphenyls were dominant speoes in soil samples,accounnng for more than 75%of ΣPCBs in the soil samples.PCB118 was the most abundant congener in all the samples.The PCB118 Was about 20%of ΣPCBs.The soil organic matter content showed only a weak correlation with the levels of all PCB congeners,in which a better correlation was noted for the more volatile lighter PCB congeners than for the heavier homologues.To a certain extent,the sources and land use seemed to influence the levels of PCBs.

  6. An invasive plant alters phenotypic selection on the vegetative growth of a native congener.

    Science.gov (United States)

    Beans, Carolyn M; Roach, Deborah A

    2015-02-01

    The ecological consequences of plant competition have frequently been tested, but the evolutionary outcomes of these interactions have gone largely unexplored. The study of species invasions can make an important contribution to this field of research by allowing us to watch ecological and evolutionary processes unfold as a novel species is integrated into a plant community. We explored the ecological and evolutionary impact of an invasive jewelweed, Impatiens glandulifera, on a closely related native congener, I. capensis and asked: (1) Does the presence of the invasive jewelweed alter the fitness of native jewelweed populations? (2) Does the invasive jewelweed affect the vegetative growth of the native congener? and (3) Does the invasive jewelweed alter phenotypic selection on the vegetative traits of the native congener? We used a greenhouse competition experiment, an invasive species removal field experiment, and a survey of natural populations. We show that when the invasive jewelweed is present, phenotypic selection favors native jewelweed individuals investing less in rapid upward growth and more in branching and fruiting potential through the production of nodes. This research demonstrates that invasive plants have the potential to greatly alter natural selection on native competitors. Studies investigating altered selection in invaded communities can reveal the potential evolutionary impact of invasive competitors, while deepening our understanding of the more general role of competition in driving plant evolution and permitting species coexistence. © 2015 Botanical Society of America, Inc.

  7. Analysis of six relevant toxaphene congeners in biological samples using ion trap MS/MS.

    Science.gov (United States)

    Gouteux, Bruno; Lebeuf, Michel; Trottier, Steve; Gagné, Jean-Pierre

    2002-10-01

    The quantification of six polychlorinated bornanes (CHBs) was studied using ion trap MS/MS. The significance of the selection of parent ions (Ip) and daughter ions (Id) on the detection of these toxaphene congeners was assessed in standard solution and biological samples. Our results indicate that different Ip and Id, selected at either low or high mass-to-charge (m/z) ratios, influence drastically the response factor of the CHBs and the chemical noise observed. For the octachlorinated toxaphene congeners (Parlar-26 (P-26), Parlar-40/41 (P-40/41), Parlar-44 (P-44)), the detection performance of the ion trap MS/MS is similar whether Ip and Id were chosen at low or high m/z ratios. However, the selection of Ip and Id at high m/z ratios clearly enhances the detection of the nonachlorinated toxaphene congeners (Parlar-50 (P-50), Parlar-62 (P-62)). The improved method, which selects Ip and Id at low m/z ratios for P-26, P-40/41 and P-44 and at high m/z ratios for P-50 and P-62, permitted to obtain low detection limits as well as repeatable and accurate results.

  8. Targeting of CD25 and glucocorticoid-induced TNF receptor family-related gene-expressing T cells differentially modulates asthma risk in offspring of asthmatic and normal mother mice.

    Science.gov (United States)

    Hubeau, Cedric; Apostolou, Irina; Kobzik, Lester

    2007-02-01

    Immunological mechanisms leading to increased asthma susceptibility in early life remain obscure. In this study, we examined the effects of neonatal Ab treatments targeting T cell populations on the development of an asthma syndrome. We used a model of increased asthma susceptibility where offspring of asthmatic BALB/c mother mice are more prone (than normal pups) to develop the disease. Neonatal pretreatment of naive pups with mAb directed against the IL-2Ralpha chain (CD25), the costimulatory molecule glucocorticoid-induced TNFR family related gene, and the inhibitory molecule CTLA-4 elicited contrasting effects in offspring depending on the mother's asthma status. Specifically, neonatal CD25(high) T cell depletion stimulated asthma susceptibility in normal offspring whereas it ameliorated the condition of pups born of asthmatic mothers. Conversely, glucocorticoid-induced TNFR family related gene ligation as a primary signal reduced the spleen cellularity and largely abrogated asthma susceptibility in asthma-prone offspring, without inducing disease in normal pups. Striking changes in Th1/Th2 cytokine levels, especially IL-4, followed mAb pretreatment and were consistent with the impact on asthma susceptibility. These results point to major differences in neonatal T cell population and responsiveness related to maternal asthma history. Interventions that temporarily remove and/or inactivate specific T cell subsets may therefore prove useful to attenuate early life asthma susceptibility and prevent the development of Th2-driven allergic airway disease.

  9. Fractionated illumination after topical application of 5-aminolevulinic acid on normal skin of hairless mice: the influence of the dark interval.

    Science.gov (United States)

    de Bruijn, H S; van der Ploeg-van den Heuvel, A; Sterenborg, H J C M; Robinson, D J

    2006-12-01

    We have previously shown that light fractionation during topical aminolevulinic acid based photodynamic therapy (ALA-PDT) with a dark interval of 2h leads to a significant increase in efficacy in both pre-clinical and clinical PDT. However this fractionated illumination scheme required an extended overall treatment time. Therefore we investigated the relationship between the dark interval and PDT response with the aim of reducing the overall treatment time without reducing the efficacy. Five groups of mice were treated with ALA-PDT using a single light fraction or the two-fold illumination scheme with a dark interval of 30 min, 1, 1.5 and 2h. Protoporphyrin IX fluorescence kinetics were monitored during illumination. Visual skin response was monitored in the first seven days after PDT and assessed as PDT response. The PDT response decreases with decreasing length of the dark interval. Only the dark interval of 2h showed significantly more damage compared to all the other dark intervals investigated (Pdark interval used. We conclude that in the skin of the hairless mouse the dark interval cannot be reduced below 2h without a significant reduction in PDT efficacy.

  10. Carnitine congener mildronate protects against stress- and haloperidol-induced impairment in memory and brain protein expression in rats.

    Science.gov (United States)

    Beitnere, Ulrika; Dzirkale, Zane; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Klusa, Vija

    2014-12-15

    The present study investigates the efficacy of mildronate, a carnitine congener, to protect stress and haloperidol-induced impairment of memory in rats and the expression of brain protein biomarkers involved in synaptic plasticity, such as brain-derived neurotrophic factor (BDNF), acetylcholine esterase and glutamate decarboxylase 67 (GAD67). Two amnesia models were used: 2h immobilization stress and 3-week haloperidol treatment. Stress caused memory impairment in the passive avoidance test and induced a significant 2-fold BDNF elevation in hippocampal and striatal tissues that was completely inhibited by mildronate. Mildronate decreased the level of GAD67 (but not acetylcholine esterase) expression by stress. Haloperidol decrease by a third hippocampal BDNF and acetylcholine esterase (but not GAD67) expression, which was normalized by mildronate; it also reversed the haloperidol-induced memory impairment in Barnes test. The results suggest the usefulness of mildronate as protector against neuronal disturbances caused by stress or haloperidol. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Dechlorination of the dietary nona-chlorinated toxaphene congeners 62 and 50 into the octa-chlorinated toxaphene congeners 44 and 40 in zebrafish (Danio rerio) and Atlantic salmon (Salmo salar)

    Energy Technology Data Exchange (ETDEWEB)

    Berntssen, M.H.G., E-mail: marc.berntssen@nifes.no [National Institute of Nutrition and Seafood Research (NIFES), Postbox 2029 Nordnes, 5817 Bergen (Norway); Lundebye, A.-K.; Hop-Johannessen, L.; Lock, E.-J. [National Institute of Nutrition and Seafood Research (NIFES), Postbox 2029 Nordnes, 5817 Bergen (Norway)

    2012-05-15

    Graphical abstract: - Abstract: The relative feed-to-fish accumulation and possible biotransformation of the nona-chlorinated toxaphene congeners currently included in EU-legislation (CHB-50 and -62) and the octa-chlorinated congeners recommended by the European Food Safety Authority to be included in future surveillance of fish samples (CHB-40, 41, and 44) were investigated in the present study. Model fish Danio rerio were fed either (a) diets spiked with a combination as well as the pure individual toxaphene congeners CHB-50 or 62 or (b) diets spiked with the combination of CHB N-Ary-Summation 50 + 62 and/or CHB N-Ary-Summation 40 + 41 + 44. In addition, seawater adapted Atlantic salmon smolts were fed technical toxaphene enriched feeds for 62 days. Zebrafish fed a diet containing CHB-50 and CHB-62 accumulated newly formed CHB-40 and 41 and CHB-44, respectively. The biomagnifications factors (BMF) of the toxaphene congeners in Atlantic salmon muscle from the feeds spiked with technical toxaphene were significantly correlated with their relative lipophilicity (expressed as log K{sub ow}). An exception was CHB-44 which had a higher BMF than could be expected from its specific log K{sub ow}, reflecting that CHB-44 is a metabolite formed under dietary exposure to CHB-62. This paper reports the in vivo dechlorination of nona-chlorinated toxaphene congeners into octa-chlorinated congeners in feeding trials with a model fish (zebrafish) and an oily food fish (Atlantic salmon).

  12. Dechlorination of the dietary nona-chlorinated toxaphene congeners 62 and 50 into the octa-chlorinated toxaphene congeners 44 and 40 in zebrafish (Danio rerio) and Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Berntssen, M H G; Lundebye, A-K; Hop-Johannessen, L; Lock, E-J

    2012-05-15

    The relative feed-to-fish accumulation and possible biotransformation of the nona-chlorinated toxaphene congeners currently included in EU-legislation (CHB-50 and -62) and the octa-chlorinated congeners recommended by the European Food Safety Authority to be included in future surveillance of fish samples (CHB-40, 41, and 44) were investigated in the present study. Model fish Danio rerio were fed either (a) diets spiked with a combination as well as the pure individual toxaphene congeners CHB-50 or 62 or (b) diets spiked with the combination of CHB ∑50+62 and/or CHB ∑40+41+44. In addition, seawater adapted Atlantic salmon smolts were fed technical toxaphene enriched feeds for 62 days. Zebrafish fed a diet containing CHB-50 and CHB-62 accumulated newly formed CHB-40&41 and CHB-44, respectively. The biomagnifications factors (BMF) of the toxaphene congeners in Atlantic salmon muscle from the feeds spiked with technical toxaphene were significantly correlated with their relative lipophilicity (expressed as logK(ow)). An exception was CHB-44 which had a higher BMF than could be expected from its specific logK(ow), reflecting that CHB-44 is a metabolite formed under dietary exposure to CHB-62. This paper reports the in vivo dechlorination of nona-chlorinated toxaphene congeners into octa-chlorinated congeners in feeding trials with a model fish (zebrafish) and an oily food fish (Atlantic salmon).

  13. Distinguishing PCB Isomeric Congeners with their Gas Chromatographic and Mass Spectrometric Ortho Effect using Comprehensive Gas Chromatography

    Science.gov (United States)

    The 209 polychlorinated biphenyl (PCB) congeners and associated nine isomeric groups (nine groups of PCBs with the same degree of chlorination) have been long recorded as high endocrine disrupting chemicals in the environment. Difficult analytical problems exist, in those frequen...

  14. Mitotic Events in Cerebellar Granule Progenitor Cells that Expand Cerebellar Surface Area Are Critical for Normal Cerebellar Cortical Lamination in Mice

    Science.gov (United States)

    Chang, Joshua C.; Leung, Mark; Gokozan, Hamza Numan; Gygli, Patrick Edwin; Catacutan, Fay Patsy; Czeisler, Catherine; Otero, José Javier

    2015-01-01

    Late embryonic and postnatal cerebellar folial surface area expansion promotes cerebellar cortical cytoarchitectural lamination. We developed a streamlined sampling scheme to generate unbiased estimates of murine cerebellar surface area and volume using stereological principles. We demonstrate that during the proliferative phase of the external granule layer (EGL) and folial surface area expansion, EGL thickness does not change and thus is a topological proxy for progenitor self-renewal. The topological constraints indicate that during proliferative phases, migration out of the EGL is balanced by self-renewal. Progenitor self-renewal must, therefore, include mitotic events yielding either 2 cells in the same layer to increase surface area (β-events) and mitotic events yielding 2 cells, with 1 cell in a superficial layer and 1 cell in a deeper layer (α-events). As the cerebellum grows, therefore, β-events lie upstream of α-events. Using a mathematical model constrained by the measurements of volume and surface area, we could quantify inter-mitotic times for β-events on a per-cell basis in post-natal mouse cerebellum. Furthermore, we found that loss of CCNA2, which decreases EGL proliferation and secondarily induces cerebellar cortical dyslamination, shows preserved α-type events. Thus, CCNA2-null cerebellar granule progenitor cells are capable of self-renewal of the EGL stem cell niche; this is concordant with prior findings of extensive apoptosis in CCNA2-null mice. Similar methodologies may provide another layer of depth to the interpretation of results from stereological studies. PMID:25668568

  15. Effect of radiation on normal hematopoiesis and on viral induced cancers of the hematopoietic system. Three-year technical progress report, August 1, 1973--April 30, 1976. [X radiation, mice

    Energy Technology Data Exchange (ETDEWEB)

    OKunewick, J.P.

    1976-01-01

    In studies conducted during the first three-year segment of this contract, it was observed that in the process of viral leukemogenesis the affected animals became more radioresistant than normal. Initial studies into the reason for the enhanced radioresistance implicated an increase in the number of pluripotent stem cells as one possible cause. During the current period, studies were carried out to further define the effect of the virus on stem cells and their kinetics using exposure to tritiated thymidine (/sup 3/HTdR) in vivo and in vitro. In addition, separate studies were initiated in an attempt to determine if the immune system played a part in the radioresistance, as well as what the effects might be of immune manipulations on the disease during the oncogenic period. Finally, studies were also undertaken to assess the sensitivity of the virus itself to radiation in vitro and in vivo to radiation and treatment with cells transplanted from viral resistant mice.

  16. Coplanar PCB congeners increase uterine weight and frontal cortical dopamine in the developing rat: implications for developmental neurotoxicity.

    Science.gov (United States)

    Seegal, Richard F; Brosch, Karl O; Okoniewski, Richard J

    2005-07-01

    We show that developmental exposure of the laboratory rat to the coplanar polychlorinated biphenyl (PCB) congener 3,4,3',4'-tetrachlorobiphenyl (TCB) and the structurally similar congener 3,4,5,3',4'-pentachlorobiphenyl (PtCB) elevates dopamine (DA) concentrations in the prefrontal cortex (PFC). To determine whether these coplanar congeners are estrogenic, and may thus contribute to the elevations in PFC DA, we measured uterine wet weight (UWW) in prepubertal rats exposed to TCB or PtCB. For comparison, additional animals were exposed to either the ortho-substituted congener 2,4,2',4'-tetrachlorobiphenyl (o-TCB) or 3,4,5,3',4',5'-hexachlorobiphenyl (HCB), a coplanar congener highly resistant to metabolism. Both TCB and PtCB increased UWW, but this effect was blocked after exposure to the anti-estrogen ICI 182,780. Neither o-TCB nor HCB altered UWW. These results demonstrate that certain coplanar PCB congeners and/or their metabolites, are estrogenic, and suggest that exposure during critical periods of neuronal development may increase central DA concentrations, and by inference, alter behavior.

  17. High levels of structural diversity observed in microcystins from Microcystis CAWBG11 and characterization of six new microcystin congeners.

    Science.gov (United States)

    Puddick, Jonathan; Prinsep, Michèle R; Wood, Susanna A; Kaufononga, Sangata A F; Cary, Stephen Craig; Hamilton, David P

    2014-11-13

    Microcystins (MCs) are cyclic peptides produced by cyanobacteria, which can be harmful to humans and animals when ingested. Differences in the coding of the non‑ribosomal peptide synthetase/polyketide synthase enzyme complex responsible for microcystin production have resulted in more than 100 microcystin variants being reported to date. The microcystin diversity of Microcystis CAWBG11 was investigated using matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography-mass spectrometry. This revealed that CAWBG11 simultaneously produced 21 known microcystins and six new congeners: [Asp3] MC-RA, [Asp3] MC-RAba, [Asp3] MC-FA, [Asp3] MC-WA, MC-FAba and MC-FL. The new congeners were putatively characterized by tandem mass spectrometry and chemical derivatization. A survey of the microcystin congeners produced by 49 cyanobacterial strains documented in scientific literature showed that cyanobacteria generally produce four microcystin congeners, but strains which produce up to 47 microcystin congeners have been reported. Microcystis CAWBG11 (which produces at least 27 congeners) was positioned in the top ten percentile of the strains surveyed, and showed fluidity of the amino acids incorporated into both position two and position four.

  18. Clarifying Normalization

    Science.gov (United States)

    Carpenter, Donald A.

    2008-01-01

    Confusion exists among database textbooks as to the goal of normalization as well as to which normal form a designer should aspire. This article discusses such discrepancies with the intention of simplifying normalization for both teacher and student. This author's industry and classroom experiences indicate such simplification yields quicker…

  19. Effect of Oligo-chitosan on Normal Intestinal Flora in Mice%甲壳低聚糖对小鼠肠道正常菌群的影响

    Institute of Scientific and Technical Information of China (English)

    任林; 陈超群; 李邦良; 薛金华; 刘小军; 高仕瑛

    2001-01-01

    Objective: To investigate the effect of olig o-chitosan on nor mal intestinal flora in mice. Methods: Twenty mice were divided randomly into an observed group and a control group. The mice in the observed group we re administered (ig) oligo-chitosan at a dose of 600 mg/(kg*d) for seven da ys. The control group were received the same volume of normal saline for seven d ays. After seven days the levels of intestinal flora were measured. Resul ts: The amount of Bifidobacteria in the observed group obviously increase d as compared with that in the control group ( P<0.05), but the number of La ctobacillus had no significant change. Conclusion: It was indicated that olig o-chitosan could adjust the intestinal flora and could stimulate the proliferat ion of Bifidobacterium in mice efficiently.%目的   观察甲壳低聚糖对小鼠肠道菌群的影响。 方法  取昆明种小鼠20只,随机分为 观察组和对照组,分别用甲壳低聚糖600 mg/(kg*d)和等体积的生理盐水灌胃, 连续7d,而后检测两组肠道菌群的变化。 结果 观察组双歧杆菌数量比对照组明显增多 (P<0.05),乳杆菌数量在两组间无明显差异,观察组大肠杆菌、肠球菌数 量较 对照组有减少趋势。结论 甲壳低聚糖具有调节小鼠肠道菌群及促进双歧杆菌增殖功能。

  20. Exposure to the three structurally different PCB congeners (PCB 118, 153, and 126) results in decreased protein expression and altered steroidogenesis in the human adrenocortical carcinoma cell line H295R.

    Science.gov (United States)

    Tremoen, Nina Hårdnes; Fowler, Paul A; Ropstad, Erik; Verhaegen, Steven; Krogenæs, Anette

    2014-01-01

    Polychlorinated biphenyls (PCB), synthetic, persistent organic pollutants (POP), are detected ubiquitously, in water, soil, air, and sediments, as well as in animals and humans. PCB are associated with range of adverse health effects, such as interference with the immune system and nervous system, reproductive abnormalities, fetotoxicity, carcinogenicity, and endocrine disruption. Our objective was to determine the effects of three structurally different PCB congeners, PCB118, PCB 126, and PCB 153, each at two concentrations, on the steroidogenic capacity and proteome of human adrenocortical carcinoma cell line cultures (H295R) . After 48 h of exposure, cell viability was monitored and estradiol, testosterone, cortisol and progesterone secretion measured to quantify steroidogenic capacity of the cells. Two-dimensional (2D) gel-based proteomics was used to screen for proteome alterations in H295R cells in response to the PCB. Exposure to PCB 118 increased estradiol and cortisol secretion, while exposure to PCB 153 elevated estradiol secretion. PCB 126 was the most potent congener, increasing estradiol, cortisol, and progesterone secretion in exposed H295R cells. Seventy-three of the 711 spots analyzed showed a significant difference in normalized spot volumes between controls (vehicle only) and at least one exposure group. Fourteen of these protein spots were identified by liquid chromatography with mass spectroscopy (LC-MS/MS). Exposure to three PCB congeners with different chemical structure perturbed steroidogenesis and protein expression in the H295R in vitro model. This study represents an initial analysis of the effects on proteins and hormones in the H295R cell model, and additional studies are required in order to obtain a more complete understanding of the pathways disturbed by PCB congeners in H295R cells. Overall, alterations in protein regulation and steroid hormone synthesis suggest that exposure to PCB disturbs several cellular processes, including

  1. Estimated PBDE and PBB Congeners in soil from an electronics waste disposal site.

    Science.gov (United States)

    Wang, H-M; Yu, Y-J; Han, M; Yang, S-W; Li, Q; Yang, Y

    2009-12-01

    This study estimated PBDE and PBB congener emissions into the environment from three different e-waste disposal sites that consisted of rude broilers (RB), acid baths (AB) and end-up dumps (ED). Different PBDE and PBB congener profiles were analyzed, and some of their emission sources were discussed. For the examined sites, the levels of SigmaPBB and SigmaPBDE were highest at ED (SigmaPBB 1943.86 ng/g, dw; SigmaPBDE 990.87 ng/g, dw), followed by RB (SigmaPBB 704.58 ng/g, dw; SigmaPBDE 799.27 ng/g, dw) and finally AB (SigmaPBB 108.78 ng/g, dw; SigmaPBDE 171.18 ng/g, dw). PBE-209 (AB 48.67 ng/g, 28.43%; RB 160.23 ng/g, 20.05%; ED 234.12 ng/g, 23.63%) and PBE-203 (AB 51.23 ng/g, 29.93%; RB 130.34 ng/g, 16.31%; ED 93.41 ng/g, 9.43%) exhibited the highest concentrations when compared to the other congeners. Furthermore, high levels of deca-BDE (BDE-209) were observed in AB (48.67 ng/g, 28.43%) and RB sites (160.23 ng/g, 20.05%), which was in accordance with the large amount of these materials in electronics products in China.

  2. Levels of toxaphene congeners in white whales (Delphinapterus leucas) from Svalbard, Norway.

    Science.gov (United States)

    Andersen, G; Føreid, S; Skaare, J U; Jenssen, B M; Lydersen, C; Kovacs, K M

    2006-03-15

    This study reports concentrations of three pesticide toxaphene congeners (CHBs; CHB-26, -50 and -62) from the blubber of ten adult, male white whales (Delphinapterus leucas) from Svalbard, Norway. The CHB congeners that occurred at the highest levels in the blubber of the white whales were, as expected, CHB-26 (4636+/-1992 (SD) ng/g l.w.) and CHB-50 (6579+/-2214 ng/g l.w.); CHB-62 (232+/-231 ng/g l.w.) was also present, but at much lower concentrations. The mean level of the sum of the three CHBs (SigmaCHBs = 11,447+/-4208 ng/g l.w.) in this study is more than twice the mean concentrations of the well-known organochlorine (OC) pollutants SigmaDDTs (sum of pp'-DDT, pp'-DDE, pp'-DDD) and SigmaPCBs (sum of 27 PCB congeners) previously reported from the same individual white whales. The concentrations of CHBs in white whales from Svalbard are at the high end of the range for concentrations of these compounds compared to other Arctic white whale populations. Additionally, the contribution of CHBs to the overall OC burden is larger in white whales from Svalbard compared with their counterparts from other areas in the Arctic. Male white whales from Svalbard have several orders of magnitude higher concentrations of SigmaCHBs compared to seals and polar bears (Ursus maritimus) from the same area. The high levels of CHBs in these whales, and their dominance in the OC pattern, suggests that white whales in Svalbard are exposed to high levels of this group of contaminants. Further studies are needed to investigate possible effects of CHBs and other OC contaminants on the white whale population in Svalbard.

  3. Low doses of ethanolic extract of Boldo (Peumus boldus) can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro, but not in cancer cells in vivo or in vitro

    Institute of Scientific and Technical Information of China (English)

    Jesmin Mondal; Kausik Bishayee; Ashis Kumar Panigrahi; Anisur Rahman Khuda-Bukhsh

    2014-01-01

    OBJECTIVE:Use of cisplatin, a conventional anticancer drug, is restricted because it generates strong hepatotoxicity by accumulating in liver. Therefore its anticancer potential can only be fully exploited if its own toxicity is considerably reduced. Towards this goal, ethanolic extract of the plant, Boldo (Peumus boldus), known for its antihepatotoxic effects, was used simultaneously with cisplatin, to test its ability to reduce cisplatin’s cytotoxicity without affecting its anticancer potential. METHODS: The cytotoxicity of Boldo extract (BE) and cisplatin, administered alone and in combination, was determined in three cancer cell lines (A549, HeLa, and HepG2) and in normal liver cells (WRL-68). Drug-DNA interaction, DNA damage, cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP, ΔΨ) were also studied. Hepatotoxicity and antioxidant activity levels were determined by alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and glutathione assays in mice. The cytotoxicity of related proteins was tested by Western blotting. RESULTS:Co-administration of BE and cisplatin increased viability of normal cells, but had no effect on the viability of cancer cells. Boldo protected liver from damage and normalized different antioxidant enzyme levels in vivo and also reduced ROS and re-polarized MMP in vitro. Bax and cytochrome c translocation was reduced with caspase 3 down-regulation. Further, a drug-DNA interaction study revealed that BE reduced cisplatin’s DNA-binding capacity, resulting in a reduction in DNA damage. CONCLUSION: Results indicated that a low dose of BE could be used beneifcial y in combination with cisplatin to reduce its toxicity without hampering cisplatin’s anticancer effect. These ifndings signify a potential future use of BE in cancer therapy.

  4. Low doses of ethanolic extract of Boldo (Peumus boldus) can ameliorate toxicity generated by cisplatin in normal liver cells of mice in vivo and in WRL-68 cells in vitro, but not in cancer cells in vivo or in vitro.

    Science.gov (United States)

    Mondal, Jesmin; Bishayee, Kausik; Panigrahi, Ashis Kumar; Khuda-Bukhsh, Anisur Rahman

    2014-09-01

    Use of cisplatin, a conventional anticancer drug, is restricted because it generates strong hepatotoxicity by accumulating in liver. Therefore its anticancer potential can only be fully exploited if its own toxicity is considerably reduced. Towards this goal, ethanolic extract of the plant, Boldo (Peumus boldus), known for its antihepatotoxic effects, was used simultaneously with cisplatin, to test its ability to reduce cisplatin's cytotoxicity without affecting its anticancer potential. The cytotoxicity of Boldo extract (BE) and cisplatin, administered alone and in combination, was determined in three cancer cell lines (A549, HeLa, and HepG2) and in normal liver cells (WRL-68). Drug-DNA interaction, DNA damage, cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP, ΔΨ) were also studied. Hepatotoxicity and antioxidant activity levels were determined by alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and glutathione assays in mice. The cytotoxicity of related proteins was tested by Western blotting. Co-administration of BE and cisplatin increased viability of normal cells, but had no effect on the viability of cancer cells. Boldo protected liver from damage and normalized different antioxidant enzyme levels in vivo and also reduced ROS and re-polarized MMP in vitro. Bax and cytochrome c translocation was reduced with caspase 3 down-regulation. Further, a drug-DNA interaction study revealed that BE reduced cisplatin's DNA-binding capacity, resulting in a reduction in DNA damage. Results indicated that a low dose of BE could be used beneficially in combination with cisplatin to reduce its toxicity without hampering cisplatin's anticancer effect. These findings signify a potential future use of BE in cancer therapy.

  5. Congener Specific Analysis of Polychlorinated Biphenyls (PCBs) in Human Blood Serum from Croatia

    OpenAIRE

    Krauthacker, Blanka; Reiner, Elsa

    2000-01-01

    A gas-chromatographic method on capillary columns is described for measuring concentrations of total PCBs and of six PCB congeners, PCB-28, PCB-52, PCB-101, PCB-138, PCB-153 and PCB-180, in human blood serum. Recovery of compounds was evaluated, and the repeatability and reproducibility of the results tested on samples analysed on the same day and over a period of two years. The method was verified in an international AQA Study in three rounds of measurements. The method was applied for the a...

  6. New GLC analysis of urushiol congeners in different plant parts of poison ivy, Toxicodendron radicans.

    Science.gov (United States)

    Craig, J C; Waller, C W; Billets, S; Elsohly, M A

    1978-04-01

    Methods are presented for the direct GLC analysis of the catechol C15 alkenyl side-chain congeners contained in the urushiol fraction of poison ivy (Toxicodendron radicans) and the C17 homologs of poison oak (Toxicodendron diversilobum). A number of liquid phases were investigated and demonstrated varying degrees of separation. The methods developed were applied to the analysis of the urushiol fractions obtained from different plant parts of poison ivy. The effects of extraction before and after drying demonstrated tht a larger percentage of urushiol was obtained when the fresh plant material was extracted with ethanol.

  7. Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

    Science.gov (United States)

    Massa, Christopher B; Groves, Angela M; Jaggernauth, Smita U; Laskin, Debra L; Gow, Andrew J

    2017-08-01

    Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd) develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs), however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group). An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical alteration at

  8. Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation.

    Directory of Open Access Journals (Sweden)

    Christopher B Massa

    2017-08-01

    Full Text Available Both aging and chronic inflammation produce complex structural and biochemical alterations to the lung known to impact work of breathing. Mice deficient in surfactant protein D (Sftpd develop progressive age-related lung pathology characterized by tissue destruction/remodeling, accumulation of foamy macrophages and alteration in surfactant composition. This study proposes to relate changes in tissue structure seen in normal aging and in chronic inflammation to altered lung mechanics using a computational model. Alterations in lung function in aging and Sftpd -/- mice have been inferred from fitting simple mechanical models to respiratory impedance data (Zrs, however interpretation has been confounded by the simultaneous presence of multiple coexisting pathophysiologic processes. In contrast to the inverse modeling approach, this study uses simulation from experimental measurements to recapitulate how aging and inflammation alter Zrs. Histologic and mechanical measurements were made in C57BL6/J mice and congenic Sftpd-/- mice at 8, 27 and 80 weeks of age (n = 8/group. An anatomic computational model based on published airway morphometry was developed and Zrs was simulated between 0.5 and 20 Hz. End expiratory pressure dependent changes in airway caliber and recruitment were estimated from mechanical measurements. Tissue elements were simulated using the constant phase model of viscoelasticity. Baseline elastance distribution was estimated in 8-week-old wild type mice, and stochastically varied for each condition based on experimentally measured alteration in elastic fiber composition, alveolar geometry and surfactant composition. Weighing reduction in model error against increasing model complexity allowed for identification of essential features underlying mechanical pathology and their contribution to Zrs. Using a maximum likelihood approach, alteration in lung recruitment and diminished elastic fiber density were shown predictive of mechanical

  9. 硫酸氨基葡萄糖对正常小鼠免疫功能的影响%Effect of glucosamine sulfate on the immunological function of normal mice

    Institute of Scientific and Technical Information of China (English)

    陈冠敏; 陈润; 张荣标; 林秀芬; 孙丽

    2011-01-01

    Objective To observe the effects of glucosamine sulfate on the immunity of normal mice. Methods Female ICR mice were divided by weight into four groups, including low dose group ( 150mg · kg-1 ) , medium dose group (300mg · kg-1 ), high dose group (900mg · kg-1 ) and normal control group. Spleen and thymus were weighted 30 days later, cch mediated immunity, humoral immunity, phagocytosis of mononuclear phagocyte and the activity of NK cell were assayed. Results The thymus index in high dose group was decreased significantly in compared with control group ( P < 0. 05 ). Compared with the control group, the delayed type hypersensitivity, serum hemolysin and the ability of antibody production were improved significantly in glucosamine suffate groups ( P <0.05). The activity of NK cell in high dose group was higher than that of the control group ( P < 0.05 ). The proliferation of spleen lymphocyte, the rate of phagocytosis and the carbon particle clearance index in all glucosamine sulfate groups were similar to those in the control group. Conclusion The immune function of normal mice could be enhanced by glucosamine sulfate, including cellular immunity, humoral immunity and the activity of NK cell.%目的 了解硫酸氨基葡萄糖对正常小鼠免疫功能的影响.方法 将ICR雌性小鼠按体重随机分成低、中、高(150、300、900mg/kg bw)3个剂量组和对照组.连续灌胃30天后,进行脾指数、胸腺指数、细胞免疫、体液免疫、NK细胞、单核-巨噬细胞及NK细胞活性的测定.结果高剂量组小鼠的胸腺指数显著高于对照组(P<0.05);中、高剂量组小鼠迟发型超敏反应(DTH)应激能力、血清溶血素水平及抗体生成能力明显高于对照组(P<0.05);高剂量组小鼠的NK细胞的活性显著高于对照组(P<0.05);硫酸氨基葡萄糖对小鼠脾淋巴细胞的增殖转化能力、腹腔巨噬细胞吞噬鸡红细胞的吞噬率、碳廓清吞噬指数均无影响.结论 硫酸氨基葡

  10. Birkhoff normalization

    NARCIS (Netherlands)

    Broer, H.; Hoveijn, I.; Lunter, G.; Vegter, G.

    2003-01-01

    The Birkhoff normal form procedure is a widely used tool for approximating a Hamiltonian systems by a simpler one. This chapter starts out with an introduction to Hamiltonian mechanics, followed by an explanation of the Birkhoff normal form procedure. Finally we discuss several algorithms for comput

  11. Short-chain chlorinated paraffins (SCCPs) in surface soil from a background area in China: occurrence, distribution, and congener profiles.

    Science.gov (United States)

    Wang, Xue-Tong; Zhang, Yuan; Miao, Yi; Ma, Ling-Ling; Li, Yuan-Cheng; Chang, Yue-Ya; Wu, Ming-Hong

    2013-07-01

    Short-chain chlorinated paraffins (SCCPs) are extremely complex technical mixtures of polychlorinated n-alkanes with carbon chain lengths from C10 to C13 and chlorine content between 49 and 70%. SCCPs are under consideration for inclusion in the Stockholm Convention on persistent organic pollutants. SCCPs have been used extensively in industrial production, but little is known about the pollution level in soil environment in China. In this study, levels and distribution of SCCPs in soil samples from Chongming Island were analyzed. Concentrations of total SCCPs in soil samples ranged from 0.42 to 420 ng g(-1), with a median of 9.6 ng g(-1). The ubiquitous occurrence of SCCPs in Chongming Island implied that long-range atmospheric transport and soil-air exchange may be the most important pathways for SCCP contamination in the background area. The localized SCCP contamination could be derived from an unidentified source. Hierarchical cluster analysis indicated that C13- and C11-congeners were predominant in most soils and C10- and C12-congeners dominated in the remaining soils. Cl7- and Cl8-congeners were on the average the most dominant chlorine congeners in nearly all soils. Principal component analysis suggested that the separation of even and odd carbon chain congeners occurred during long-range atmospheric transport and aging in soil in the study area.

  12. Levels and congener specific profiles of PBDEs in human breast milk from China: implication on exposure sources and pathways.

    Science.gov (United States)

    Sudaryanto, Agus; Kajiwara, Natsuko; Tsydenova, Oyuna V; Isobe, Tomohiko; Yu, Hongxia; Takahashi, Shin; Tanabe, Shinsuke

    2008-11-01

    Fourteen PBDE congeners from mono- to deca-BDE were determined in breast milk of primiparous mothers from two locations in East China, i.e. Nanjing (n=9), an urban area, and Zhoushan (n=10), a semi rural coastal area. PBDEs were detected in all the human breast milk samples of the present study, indicating that general population in these two locations are widely exposed to these pollutants. Relatively higher concentrations of PBDEs were found in the milk of mothers from Nanjing than Zhoushan, suggesting the existence of significant sources of PBDEs in urban areas. PBDE levels in the present study were similar to those in European countries, but one or two orders of magnitude lower than in North America. Except for BDE-3, all congeners from di- to deca-BDE were detected in the samples of the present study. BDE-209, a congener considered to have less bioavailability, was detected in about 50% of the samples at concentrations higher than that of other congeners. Other higher brominated congeners, such as BDE-153, -197 and -207, were also prominent in the present study, which is different from the pattern generally observed in previous studies on human milk as well as biota samples. These results may indicate that the inhabitants of Nanjing and Zhoushan are exposed to location specific sources of PBDEs.

  13. Chemical fingerprinting and phylogenetic mapping of saponin congeners from three tropical holothurian sea cucumbers.

    Science.gov (United States)

    Bondoc, Karen Grace V; Lee, Hyeyoung; Cruz, Lourdes J; Lebrilla, Carlito B; Juinio-Meñez, Marie Antonette

    2013-01-01

    Holothurians are sedentary marine organisms known to produce saponins (triterpene glycosides), secondary metabolites exhibiting a wide range of biological activities. In this paper, we investigated the saponin contents of semi-purified and membranolytic HPLC fractionated extracts from the body wall of three species of Holothuriidae as an attempt to examine its chemical diversity in relation to phylogenetic data. MALDI-FTICR MS and nano-HPLC-chip Q-TOF MS were used for mass profiling and isomer separation, respectively giving a unique chemical saponin fingerprint. Moreover, the methods used yield the highest number of congeners. However, saponin concentration, bioactivity and chemical diversity had no apparent relationship. MS fingerprint showed the presence of holothurinosides, which was observed for the first time in other Holothuria genera besides the basally positioned Holothuria forskali. This congener is proposed to be a primitive character that could be used for taxonomic purposes. The phylogenetic mapping also showed that the glycone part of the compound evolved from non-sulfated hexaosides to sulfated tetraosides, which have higher membranolytic activity and hydrophilicity, the two factors affecting the total ecological activity (i.e. chemical defense) of these compounds. This might be an adaptation to increase the fitness of the organism.

  14. SAR of Sponge-Inspired Hemibastadin Congeners Inhibiting Blue Mussel PhenolOxidase

    Directory of Open Access Journals (Sweden)

    Hendrik Niemann

    2015-05-01

    Full Text Available Hemibastadin derivatives, including the synthetically-derived 5,5′-dibromohemibastadin-1 (DBHB, are potent inhibitors of blue mussel phenoloxidase (PO, which is a key enzyme involved in the firm attachment of this invertebrate to substrates and, thus, a promising molecular target for anti-fouling research. For a systematic investigation of the enzyme inhibitory activity of hemibastadin derivatives, we have synthesized nine new congeners, which feature structural variations of the DBHB core structure. These structural modifications include, e.g., different halogen substituents present at the aromatic rings, different amine moieties linked to the (E-2-(hydroxyimino-3-(4-hydroxyphenylpropionic acid, the presence of free vs. substituted aromatic hydroxyl groups and a free vs. methylated oxime group. All compounds were tested for their inhibitory activity towards the target enzyme in vitro, and IC50 values were calculated. Derivatives, which structurally closely resemble sponge-derived hemibastadins, revealed superior enzyme inhibitory properties vs. congeners featuring structural moieties that are absent in the respective natural products. This study suggests that natural selection has yielded structurally-optimized antifouling compounds.

  15. Linking habitat use of Hudson River striped bass to accumulation of polychlorinated biphenyl congeners

    Energy Technology Data Exchange (ETDEWEB)

    Ashley, J.T.F.; Secor, D.H.; Zlokovitz, E.; Wales, S.Q.; Baker, J.E.

    2000-03-15

    Since 1976, the commercial striped bass fishery in the Hudson River (NY) has been closed due to total polychlorinated biphenyl (t-PCB) concentrations that exceed the US Food and Drug Administration's advisory level of 2 {micro}g/g-wet weight. Extensive monitoring of Hudson River striped bass demonstrated much more variability in t-PCB levels among individual striped bass than could be explained by their age, sex, or lipid contents. To investigate the possible role of differential habitat use among subpopulations of striped bass in controlling their PCB exposures, 70 fish collected throughout the Hudson River estuary and Long Island Sound in 1994--1995 were analyzed for PCB congeners, and their lifetime migration behaviors were estimated by otolith microchemistry. The mean salinity encountered during the fish's last growth season prior to capture was inversely correlated with the t-PCB body burden. Striped bass permanently residing in fresh and oligohaline portions of the estuary adjacent to known PCB sources had elevated t-PCB levels and congeneric patterns with higher proportions of di-, tri-, and tetrachlorobiphenyls. Conversely, fish spending the majority of their life in more saline waters of the estuary or migrating frequently throughout the salinity gradient contained lower PCB levels composed of more highly chlorinated congeners. The approach used in this study allows habitat use to be incorporated into exposure assessments for anadromous fish species such as striped bass.

  16. Microhabitat distribution of two Florida scrub endemic plants in comparison to their habitat-generalist congeners.

    Science.gov (United States)

    Maliakal-Witt, Satya; Menges, Eric S; Denslow, J S

    2005-03-01

    Habitat-specialist species may be restricted to a narrower range of microhabitats than habitat-generalist species. We addressed this hypothesis by comparing microhabitats of two pairs of congeners that differ in habitat specificity and co-occur in one distinct habitat type, Florida rosemary scrub. We characterized microhabitats of rosemary scrub specialists, Polygonella basiramia and Lechea cernua, their habitat-generalist congeners, Polygonella robusta and Lechea deckertii, and random points in the rosemary scrub habitat. Plants of both habitat specialists occurred in microhabitats with significantly more bare sand than plants of habitat-generalist species and random points. Plants of all four species occurred in microhabitats that were farther from dominant shrubs, Ceratiola and Quercus spp., than random points. Seedlings of both habitat specialists grew larger in bare sand microhabitats, whereas ground lichens and litter did not affect seedling growth of the habitat generalists. As the time since fire increases, bare sand cover decreases, Ceratiola density increases, Quercus density remains constant, and shrubs become taller. Physical characteristics, such as soil temperature, soil carbon, and soil moisture, differ slightly with respect to microhabitat. Our results suggest that P. basiramia and L. cernua are specialized on bare sand microhabitats that characterize their preferred habitat, rosemary scrub. Microhabitat specialization may limit the distribution of these rare species.

  17. Association between tryptophan hydroxylase-2 genotype and the antidepressant effect of citalopram and paroxetine on immobility time in the forced swim test in mice.

    Science.gov (United States)

    Kulikov, Alexander V; Tikhonova, Maria A; Osipova, Daria V; Kulikov, Victor A; Popova, Nina K

    2011-10-01

    Tryptophan hydroxylase-2 (TPH2) is the rate limiting enzyme of serotonin synthesis in the brain. The 1473G allele of the C1473G polymorphism in mTPH2 gene is associated with reduced enzyme activity and serotonin synthesis rate in the mouse brain. Here, the influence of the 1473G allele on the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs), citalopram (2.5 or 5.0mg/kg) and paroxetine (5.0 or 10.0mg/kg), in the forced swim test was studied using B6-1473G and B6-1473C congenic mouse lines with the 1473G (decreased TPH2 activity) or 1473C (normal TPH2 activity) alleles, respectively, transferred to the genome of C57BL/6 mouse strain. Paroxetine (5.0 or 10.0mg/kg) and citalopram (2.5 or 5.0mg/kg) decreased immobility time in B6-1473C mice, while both doses of paroxetine and 2.5mg/kg of citaloprame did not alter immobility time in B6-1473G mice. However, 5.0mg/kg of citalopram reduced immobility in B6-1473G mice. The results provided genetic evidence of moderate association between 1473G allele and reduced sensitivity to SSRIs in mice.

  18. A model of Salmonella colitis with features of diarrhea in SLC11A1 wild-type mice.

    Directory of Open Access Journals (Sweden)

    Heungjeong Woo

    Full Text Available BACKGROUND: Mice do not get diarrhea when orally infected with S. enterica, but pre-treatment with oral aminoglycosides makes them susceptible to Salmonella colitis. However, genetically susceptible ItyS mice (Nramp1(G169D allele die from systemic infection before they develop diarrhea, so a new model is needed to study the pathogenesis of diarrhea. We pretreated ItyR mice (Nramp1(G169 with oral kanamycin prior to infecting them with virulent S. Typhimurium strain 14028s in order to study Salmonella-induced diarrhea. We used both a visual scoring system and the measurement of fecal water content to measure diarrhea. BALB/c.D2(Nramp1 congenic started losing weight 5 days post-infection and they began to die from colitis 10-14 days after infection. A SPI-1 (invA mutant caused cecal, but not colonic inflammation and did not cause diarrhea. A phoP- mutant did not cause manifestations of diarrhea in either normal or NADPH-deficient (gp91(phox mice. However, strain 14028s caused severe colitis and diarrhea in gp91(phox-deficient mice on an ItyR background. pmr A and F mutants, which are less virulent in orally infected BALB/c mice, were fully virulent in this model of colitis. CONCLUSIONS: S. enterica must be able to invade the colonic epithelium and to persist in the colon in order to cause colitis with manifestations of diarrhea. The NADPH oxidase is not required for diarrhea in Salmonella colitis. Furthermore, a Salmonella phoP mutant can be cleared from the colon by non-oxidative host defenses.

  19. Concentration of polychlorinated biphenyl (PCB) congeners in the muscle of Clarias gariepinus and sediment from inland rivers of southwestern Nigeria and estimated potential human health consequences.

    Science.gov (United States)

    Adeogun, Aina O; Chukwuka, Azubuike V; Okoli, Chukwunonso P; Arukwe, Augustine

    2016-01-01

    The distributions of polychlorinated biphenyl (PCB) congeners were determined in sediment and muscle of the African sharptooth catfish (Clarias gariepinus) from the Ogun and Ona rivers, southwest Nigeria. In addition, the effect of PCB congeners on condition factor (CF) and associated human health risk was assessed using muscle levels for a noncarcinogenic hazard quotient (HQ) calculation. Elevated concentrations of high-molecular-weight (HMW) PCB congeners were detected in sediment and fish downstream of discharge points of both rivers. A significant reduction in fish body weight and CF was observed to correlate with high PCB congener concentrations in the Ona River. A principal component (PC) biplot revealed significant site-related PCB congener distribution patterns for HMW PCB in samples from the Ogun River (71.3%), while the Ona River (42.6%) showed significant PCB congener patterns for low-molecular-weight (LMW) congeners. Biota-sediment accumulation factor (BSAF) was higher downstream for both rivers, presenting PCB congener-specific accumulation patterns in the Ona River. Significant decreases in fish body weight, length and CF were observed downstream compared to upstream in the Ona River. The non-carcinogenic HQ of dioxin-like congener 189 downstream in both rivers exceeded the HQ = 1 threshold for children and adults for both the Ogun and Ona rivers. Overall, our results suggest that industrial discharges contribute significantly to PCB inputs into these rivers, with potential for significant health implications for neighboring communities that utilize these rivers for fishing and other domestic purposes.

  20. Natural suppressor cells in spleens of irradiated, bone marrow-reconstituted mice and normal bone marrow: Lack of Sca-1 expression and enrichment by depletion of Mac1-positive cells

    Energy Technology Data Exchange (ETDEWEB)

    Sykes, M.; Sharabi, Y.; Sachs, D.H. (National Cancer Institute, Bethesda, MD (USA))

    1990-05-01

    We have recently reported the development of natural suppressor (NS) cells in lethally irradiated, bone marrow-reconstituted mice during the early weeks after bone marrow transplantation (BMT). These cells were shown to be derived primarily from the syngeneic marrow component in recipients of mixed allogeneic plus syngeneic (host type) marrow, and it was speculated that they might be responsible for the anti-GVHD effect previously described for T-cell-depleted syngeneic marrow. It was therefore of interest to look for such suppressive activity in normal adult bone marrow, which might serve as an obtainable source of such cells if they were to be isolated and used clinically. Such activity has indeed been found in normal adult bone marrow and its characteristics compared to that in spleens of early BMT recipients. Suppressive cells from both sources were similar in their specificity patterns and radiosensitivity, and were of the null (i.e., non-T, non-B, nonmacrophage) cell phenotype. Suppression from either source can be enriched by removal of Mac1-positive cells, providing a possible approach to obtaining NS-enriched populations for in vitro expansion and adoptive transfer studies. Such depletion of Mac1-positive cells was associated with a threefold enrichment of Thy1-positive cells, of which one half were CD4- and CD8-negative, similar to the reported phenotype of cultured NS cell lines. Even when enriched in this manner, the contribution of Thy1-positive cell populations did not reach statistical significance. A recent report has suggested that NS cells might actually be pluripotent hematopoietic stem cells. In contrast, we report here that depletion of Sca1-positive pluripotent hematopoietic stem cells with monoclonal antibody plus immunomagnetic beads does not remove NS activity.

  1. Determination of toxaphene specific congeners in fish liver oil and feedingstuff using gas chromatography coupled to high resolution mass spectrometry.

    Science.gov (United States)

    Veyrand, Bruno; Venisseau, Anaïs; Marchand, Philippe; Antignac, Jean-Philippe; Le Bizec, Bruno

    2008-04-01

    A new method for the determination of nine toxaphene specific congeners in fish liver oil and feedingstuff has been developed. The samples were extracted using pressurized liquid extraction followed by a purification on silica and florisil columns. Identification and quantification were conducted using GC-(EI)-HRMS, and comparison with MS/MS detection was performed, using electron ionization and negative chemical ionization. Limits of detection were ranged from 0.01 to 0.22 microg kg(-1) (12% moisture) as required for feed samples. The calibration curves showed a good linearity for all congeners (R(2)>0.99). Repeatability was below 9% for all the congeners and recoveries were in-between 73 and 86%. This analytical method was applied to the quantification of thirteen real samples collected within national monitoring plans for further risk assessment.

  2. Effects of in ovo exposure to PCBs (coplanar congener, kanechlor mixture, hydroxylated metabolite) on the developing cell-mediated immunity in chickens

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, J.; Matsuda, M.; Kawano, M.; Wakimoto, T. [Faculty of Agriculture, Ehime Univ., Matsuyama, Ehime (Japan); Kashima, Y. [Dept. of Hygiene, Yokohama City Univ. School of Medicine, Yokohama (Japan)

    2004-09-15

    Polychlorinated biphenyls (PCBs) are wide spread environmental contaminants and known to cause various adverse effects on health of human and wildlife. Immune system is one of the several targets for toxic effects of PCBs and its normal balance is often disrupted by the exposure of the compounds. For example, PCBs may induce immune suppression and result in increased susceptibility to bacterial and viral infections, or conversely, excessive immune enhancement may cause adverse outcomes including as autoimmune disease and anergy. Therefore immune function is regarded as one of an important endpoint in toxicological risk assessment. There are a number of studies shown that neonatal organisms perinatally exposed to polyhalogenated aromatic hydrocarbons (PHAHs) such as PCBs have severer effects on their immune system than adult. Dioxins and coplanar PCB congeners, structurally planar PHAHs are known to have high affinity for aryl hydrocarbon receptor (AhR). 2,3,7,8-tetrachlorinated dibenzo-p-dioxin (TCDD) have the strongest affinity among such compounds and these are considered to act on immune system through AhR. On the other hand, such as non-planar PCB congeners with low affinity for AhR, which are abundantly contained in commercial PCB preparations have non-additive (antagonistic) effects on immune function. Prenatal exposure of TCDD to rodent induced abnormal lymphoid development in the thymus and thymus-dependent immune functions were remarkably disturbed. Although several experimental studies in mammals have been carried out on the developmental immunotoxicity of PCBs, there are still limited information available on avian species. Thus in this study, prenatal exposure to low level of PCBs and the effects on the developing immune system were investigated with chicken as a model animal of avian species, especially it is focused on the cell-mediated immune function.

  3. Comparative analysis of radiation- and virus-induced leukemias in BALB/c mice

    Energy Technology Data Exchange (ETDEWEB)

    Newcomb, E.W.; Binari, R.; Fleissner, E.

    1985-01-15

    Endogenous murine leukemia virus (MuLV) proviral copies were analyzed in thymomas induced in normal BALB/c (Fv-1b) and in Fv-1n congenic mice by X-irradiation. Both strains of mice developed leukemia with similar kinetics, indicating that N-tropism of endogenous MuLV was not a rate-limiting factor in development of disease. Southern blot analysis, using a probe specific for ecotropic virus and for ecotropic-specific sequences retained in pathogenic, env-recombinant viruses, showed that the majority of radiation leukemias lacked newly acquired, clonally integrated, proviruses. This was in contrast to virus-induced leukemias, which routinely exhibited several new proviral integration sites. When an internal proviral DNA restriction fragment was monitored, some radiation leukemias showed evidence of nonclonal infection, accounting for more frequent isolation of infectious virus from such leukemias. Differences in expression of T-cell surface antigens were found in X-ray-induced and virus-induced leukemias. All radiation leukemias were TL positive, whereas virus-induced leukemias were primarily negative for TL. Some differences were also found in Lyt-1 and Lyt-2 expression. The data as a whole suggest that, in the majority of cases, radiation leukemogenesis is not initiated by a viral route--that is, the sort of viral mechanism for which exogenous infection by known pathogenic MuLV is the paradigm.

  4. Reduction of thyroid hormone levels by methylsulfonyl metabolites of polychlorinated biphenyl congeners in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yoshihisa; Shibahara, Tomoo; Kimura, Ryohei [School of Pharmaceutical Sciences, University of Shizuoka (Japan); Haraguchi, Koichi; Masuda, Yoshito [Daiichi College of Pharmaceutical Sciences, Fukuoka (Japan)

    1998-07-01

    Male Sprague-Dawley rats received four consecutive intraperitoneal doses of four kinds of methylsulfonyl (MeSO{sub 2}) metabolites of polychlorinated biphenyl (PCB) congeners: 3-MeSO{sub 2}-2,2`,3`,4`,5,6-hexachlorobiphenyl (3-MeSO{sub 2}-CB132); 3-MeSO{sub 2}-2,2`,3`,4`, 5,5`-hexachlorobiphenyl (3-MeSO{sub 2}-CB141); 3-MeSO{sub 2}-2,2`,4`,5,5`,6-hexachlorobiphenyl (3-MeSO{sub 2}-CB149) and 4-MeSO{sub 2}-2,2`,4`,5,5`,6-hexachlorobiphenyl (4-MeSO{sub 2}-CB149). The congeners were major MeSO{sub 2}-PCBs determined in human milk, liver and adipose tissue, and the aim was to determine their effect on thyroid hormone levels. All four tested MeSO{sub 2} metabolites (20 {mu}mol/kg once daily for 4 days) reduced serum total thyroxine levels by 22-44% at a much lower dose than phenobarbital (PB; 431 {mu}mol/kg once daily for 4 days) on days 2, 3, 4 and 7 after the final doses. Total triiodothyronine levels were reduced 37% by treatment with 4-MeSO{sub 2}-CB149 at day 7. A 30% increase in thyroid weight was produced by 3-MeSO{sub 2}-CB141 treatment. Total cytochrome P450 content was increased by 3-MeSO{sub 2}-CB132, 3-MeSO{sub 2}-CB141 and 3-MeSO{sub 2}-CB149, but not by 4-MeSO{sub 2}-CB149. Thus, it is likely that the 3-MeSO{sub 2}-hexachlorobiphenyls and 4-MeSO{sub 2}-CB149 could influence the thyroid hormone metabolism by different mechanism(s). The results show that tested 3- and 4-MeSO{sub 2} metabolites of PCB congeners reduce thyroid hormone levels much more than PB in rats. Our finding suggests that the metabolites may act as endocrine-disrupters. (orig.) With 2 figs., 1 tab., 25 refs.

  5. Four new doramectin congeners with acaricidal and insecticidal activity from Streptomyces avermitilis NEAU1069.

    Science.gov (United States)

    Wang, Xiang-Jing; Zhang, Ji; Wang, Ji-Dong; Huang, Sheng-Xiong; Chen, Yi-Hua; Liu, Chong-Xi; Xiang, Wen-Sheng

    2011-11-01

    Four new doramectin congeners, 1-4, were isolated from Streptomyces avermitilis NEAU1069. The structures of 1-4 were elucidated on the basis of spectroscopic analysis, including 1D- and 2D-NMR as well as HR-ESI-MS, ESI-MS, UV, and IR, and comparison with literature data. All compounds exhibited noticeable acaricidal and insecticidal activities. Especially compound 2 was found to be the most potent pesticide of the compounds evaluated with the IC(50) values of 10.2, 65.1 and 124.4 μg/ml against adult two-spotted spider mites (Tetranychus urticae Koch), two-spotted spider mite eggs, and Mythimna separata, respectively, which are comparable to those of commercial pesticide milbemycin A(3)/A(4) as positive reference.

  6. Rhizospere Redox Cycling and Implications for Rhizosphere Biotransformation of Selected Polychlorinated Biphenyl (PCB) Congeners.

    Science.gov (United States)

    Meggo, Richard E; Schnoor, Jerald L

    2013-08-01

    Theoretically, sequential cycles of dechlorination followed by aerobic bio-oxidation are desirable to achieve complete degradation of a mixture of higher and lower chlorinated PCBs. In this research, soil was artificially contaminated with polychlorinated biphenyls (PCBs) in mixture and as single congeners, aged, and planted with two different plant species. Alternating redox cycles were created in the root zone of plants by flooding and draining the soil. Over 32 weeks, switchgrass (Panicum virgatum) and poplar (Populus deltoids x nigra DN34) planted systems that were exposed to alternate cycles of flooding performed better in reducing parent PCBs than planted systems that were not cycled (p<0.05). The cycled systems also had a higher mass of PCB transformation products than the uncycled systems. Multiple cycles were necessary to achieve significant differences between the cycled and uncycled treatments.

  7. Gateway synthesis of daphnane congeners and their protein kinase C affinities and cell-growth activities

    Science.gov (United States)

    Wender, Paul A.; Buschmann, Nicole; Cardin, Nathan B.; Jones, Lisa R.; Kan, Cindy; Kee, Jung-Min; Kowalski, John A.; Longcore, Kate E.

    2011-08-01

    The daphnane diterpene orthoesters constitute a structurally fascinating family of natural products that exhibit a remarkable range of potent biological activities. Although partial activity information is available for some natural daphnanes, little information exists for non-natural congeners or on how changes in structure affect mode of action, function, potency or selectivity. A gateway strategy designed to provide general synthetic access to natural and non-natural daphnanes is described and utilized in the synthesis of two novel members of this class. In this study, a commercially available tartrate derivative was elaborated through a key late-stage diversification intermediate into B-ring yuanhuapin analogues to initiate exploration of the structure-function relationships of this class. Protein kinase C was identified as a cellular target for these agents, and their activity against human lung and leukaemia cell lines was evaluated. The natural product and a novel non-natural analogue exhibited significant potency, but the epimeric epoxide was essentially inactive.

  8. Synthesis and biological evaluation of novel biaryl type α-noscapine congeners.

    Science.gov (United States)

    Manchukonda, Naresh K; Naik, Pradeep K; Sridhar, Balasubramanian; Kantevari, Srinivas

    2014-12-15

    Natural α-noscapine, a known antitussive drug, is also now known to possess weak anticancer efficacy with relatively safe toxicity profile. In this study, we report synthesis and evaluation of novel biaryl type α-noscapine congeners designed by adding aryl unit to the tetrahydroisoquinoline part of natural α-noscapine core. Palladium catalyzed Suzuki cross coupling of 9-bromo α-noscapine with aryl boronic acids was employed using mild and inexpensive reagents to attain desired noscapinoids 5a-g in excellent yields. Screening anti-proliferative activity for new noscapinoids 5b-g, on human cancer cell lines resulted three compounds 5b, 5d and 5f as potent analogues, active against human breast epithelial (MCF-7), human cervix cancer (HeLa) and human lung adenocarcinoma epithelial (A549) cell lines.

  9. Do settlement dynamics influence competitive interactions between an alien tunicate and its native congener?

    Science.gov (United States)

    Bouchemousse, Sarah; Lévêque, Laurent; Viard, Frédérique

    2017-01-01

    Variation in density of early stages, that is, larvae and juveniles, is a major determinant of the distribution and abundance of the adult population of most marine invertebrates. These early stages thus play a key role in competitive interactions, and, more specifically, in invasion dynamics when biologically similar native and non-native species (NNS) come into contact in the same habitat. We examined the settlement dynamics and settlement rate of two important members of the fouling community that are common on human-made infrastructures around the world: Ciona robusta (formerly known as Ciona intestinalis type A) and C. intestinalis (formerly known as C. intestinalis type B). In the western English Channel, the two species live in close syntopy following the recent introduction of C. robusta in the native European range of C. intestinalis. Using settlement panels replaced monthly over 2 years in four marinas (including one studied over 4 years) and species-diagnostic molecular markers to distinguish between juveniles of both species (N = 1,650), we documented similar settlement dynamics of both species, with two settlement periods within a calendar year. With one exception, settlement times were highly similar in the congeners. Although the NNS showed lower settlement density than that of the native congener, its juvenile recruitment was high during the second settlement period that occurs after the warm season, a pattern also observed in adult populations. Altogether, our results suggest that species' settlement dynamics do not lead to the dominance of one species over the other through space monopolization. In addition, we showed that changes over time are more pronounced in the NNS than in the native species. This is possibly due to a higher sensitivity of the NNS to changes of environmental factors such as temperature and salinity. Environmental changes may thus eventually modify the strength of competitive interactions between the two species as

  10. Novel double-congenic strain reveals effects of spontaneously hypertensive rat chromosome 2 on specific lipoprotein subfractions and adiposity.

    Science.gov (United States)

    Seda, Ondrej; Sedová, Lucie; Liska, Frantisek; Krenová, Drahomíra; Prejzek, Vratislav; Kazdová, Ludmila; Tremblay, Johanne; Hamet, Pavel; Kren, Vladimír

    2006-10-01

    We have developed a new, double-congenic rat strain BN-Lx.SHR2, which carries two distinct segments of chromosome 2 introgressed from the spontaneously hypertensive rat strain (SHR) into the genetic background of congenic strain BN-Lx, which was previously shown to express variety of metabolic syndrome features. In 16-wk-old male rats of BN-Lx and BN-Lx.SHR2 strains, we compared their glucose tolerance and triacylglycerol and cholesterol concentrations in 20 lipoprotein subfractions and the lipoprotein particle sizes under conditions of feeding standard and high-sucrose diets. Introgression of two distinct SHR-derived chromosome 2 segments resulted in decreased adiposity together with aggravation of glucose intolerance in the double-congenic strain. The BN-Lx.SHR2 rats were more sensitive to sucrose-induced rise in triacylglycerolemia. Although the total cholesterol concentrations of the two strains were comparable after the standard diet and even lower in BN-Lx.SHR2 after sucrose feeding, detailed analysis revealed that under both dietary conditions, the double-congenic strain had significantly higher cholesterol concentrations in low-density lipoprotein fractions and lower high-density lipoprotein fractions. We established a new inbred model showing dyslipidemia and mild glucose intolerance without obesity, attributable to specific genomic regions. For the first time, the chromosome 2 segments of SHR origin are shown to influence other than blood pressure-related features of metabolic syndrome or to be involved in relevant nutrigenomic interactions.

  11. HIGH RESOLUTION MODELLING OF PCB CONGENERS IN LAKE MICHIGAN USING THE LAKE MICHIGAN (LM3) CONTAMINANT MODEL

    Science.gov (United States)

    The Lake Michigan Level 3 (LM3) Model is a numerical model of Lake Michigan used to predict the fate and transport of 54 PCB congeners. The LM3 model segments Lake Michigan horizontally with a 5 x 5 km grid and vertically with 19 sigma layers for a total of 44,042 water column se...

  12. Response to Ecological Risk Assessment Forum Request for Information on the Benefits of PCB Congener-Specific Analyses

    Science.gov (United States)

    In August, 2001, the Ecological Risk Assessment Forum (ERAF) submitted a formal question to the Ecological Risk Assessment Support Center (ERASC) on the benefits of evaluating PCB congeners in environmental samples. This question was developed by ERAF members Bruce Duncan and Cla...

  13. Analysis of major congeners of polybromobiphenyls and polybromodiphenyl ethers in office dust using high resolution gas chromatography-mass spectrometry.

    Science.gov (United States)

    Kefeni, Kebede K; Okonkwo, Jonathan O

    2012-05-01

    The study focused on analysis of polybromobiphenyls (PBBs) and polybromodiphenyl ethers (PBDEs) congeners in office dust obtained in Pretoria, South Africa. Of the 32 congeners considered for identification, (BB-1, 2, 4, 10, 15, 26, 29, 30, 31, 38, 49, 80, 103, 153, 155, 209 and BDE-3, 15, 17, 28, 47, 66, 77, 85, 99, 100, 126, 138, 153, 154, 183, 209) only BB-2, 4, 30, 153, 209 and BDE-47, 66, 85, 99, 153 and 209 congeners were detected. The sum of PBBs concentration detected in office dust ranged from congeners detected. Concentrations of PBDEs detected in this study are substantially lower than reported in office dust in developed countries.

  14. Segregated Foxc2, NFATc1 and Connexin expression at normal developing venous valves, and Connexin-specific differences in the valve phenotypes of Cx37, Cx43, and Cx47 knockout mice.

    Science.gov (United States)

    Munger, Stephanie J; Geng, Xin; Srinivasan, R Sathish; Witte, Marlys H; Paul, David L; Simon, Alexander M

    2016-04-15

    Venous valves (VVs) are critical for unidirectional blood flow from superficial and deep veins towards the heart. Congenital valve aplasia or agenesis may, in some cases, be a direct cause of vascular disease, motivating an understanding of the molecular mechanisms underlying the development and maintenance of VVs. Three gap junction proteins (Connexins), Cx37, Cx43, and Cx47, are specifically expressed at VVs in a highly polarized fashion. VVs are absent from adult mice lacking Cx37; however it is not known if Cx37 is required for the initial formation of valves. In addition, the requirement of Cx43 and Cx47 for VV development has not been studied. Here, we provide a detailed description of Cx37, Cx43, and Cx47 expression during mouse vein development and show by gene knockout that each Cx is necessary for normal valve development. The valve phenotypes in the knockout lines exhibit Cx-specific differences, however, including whether peripheral or central VVs are affected by gene inactivation. In addition, we show that a Cx47 null mutation impairs peripheral VV development but does not affect lymphatic valve formation, a finding of significance for understanding how some CX47 mutations cause inherited lymphedema in humans. Finally, we demonstrate a striking segregation of Foxc2 and NFATc1 transcription factor expression between the downstream and upstream faces, respectively, of developing VV leaflets and show that this segregation is closely associated with the highly polarized expression of Cx37, Cx43, and Cx47. The partition of Foxc2 and NFATc1 expression at VV leaflets makes it unlikely that these factors directly cooperate during the leaflet elongation stage of VV development.

  15. Enantioselective determination of chiral toxaphene congeners in laying hens and eggs using multidimensional high-resolution gas chromatography.

    Science.gov (United States)

    Hamed, Sobhy; Leupold, Guenter; Ismail, Ahmed; Parlar, Harun

    2005-09-07

    A total of 22 chiral toxaphene congeners were analyzed in organ tissues and eggs of laying hens after they had been fed with food spiked with technical toxaphene. For the analysis, multidimensional high-resolution gas chromatography using a chiral column coated with randomly silylated heptakis(O-tert-butyldimethylsilyl)-beta-cyclodextrin, electron capture detection, and valveless "live column switching" technique was applied. The analytical results were additionally confirmed with mass spectral data, recorded in electron-capture negative ionization mode with selected-ion monitoring mass spectrometry. During both the feeding period of the laying hens with toxaphene-contaminated food (38 weeks, accumulation phase) and the following subsiding period without toxaphenes (another 14 weeks, decontamination phase), organs (liver, kidney, skin/fat), blood, meat, and eggs of the hens served as model matrices for toxaphene uptake. The enantiomeric ratios (ERs) of congeners 26, 31, 32, 40, 41, 42(a+b), 44, 50, and 62--known as the most important components of technical toxaphene occurring in the environment--could be analytically determined. Significant differences were observed with respect to their initial racemic ratios. On the basis of their chemical structures, the metabolic pathways of some congeners could be explained. Astonishingly, some of the toxaphenes applied as racemates could merely be found as single enantiomers at the end of the feeding program, for example, congener 32 in blood and meat samples or congener 44, especially in organ tissues, which showed ERs of zero or infinity. The findings of this study impressively emphasize that it is essential to isolate and analyze individual toxaphene enantiomers in food and biota tissues to be capable of evaluating their toxicity and metabolization more specifically.

  16. CD4+ T lymphocytes injected into severe combined immunodeficient (SCID) mice lead to an inflammatory and lethal bowel disease

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg; Rudolphi, A; Kofoed, S

    1996-01-01

    Transfer of 2 x 10(5) congenic or semiallogenic purified TCR alphabeta+ CD4+ T cells to SCID mice leads to an infiltration of the recipient gut lamina propria and epithelium with a donor-derived CD4+ T cell subset which induces a lethal inflammatory bowel disease (IBD) in the recipients. In contr...

  17. [Analysis of toxaphene and its eight congeners in sediment and fish tissue by gas chromatography-negative ion mass spectrometry].

    Science.gov (United States)

    Lao, Wenjian

    2013-07-01

    Toxaphene quantification incorporating gas chromatography/negative chemical ionization mass spectrometry (GC/NCI-MS) offers improved sensitivity and specificity. The U. S. Environmental Protection Agency (USEPA) recently released a GC/NCI-MS method (Method 8276) for the measurement of technical toxaphene and eight specific congeners (Hx-Sed, Hp-Sed, P26, P41, P40, P44, P50 and P62). However, there is still lack of a practical and complete analytical method including sample extraction, clean up, instrumental analysis, and data analysis. The goal of this work was to develop a ready-to-use method for the quantification of total toxaphene and the eight congeners. Sediment and salmon fish tissue were selected as sample matrices and extracted with methylene chloride using an accelerated solvent extraction system. The sample extracts were cleaned up with active copper powder or gel permeation chromatography, and finally silica/alumina combination column. Separation was performed on a DB-XLB column. GC/NCI-MS was operated under selected ion monitoring mode with an identical set of confirmation and quantitation ions for total toxaphene and the eight congeners. Oxygen reaction of polychlorinated biphenyls (PCB) was monitored by PCB204, an internal calibration standard, and the reaction level was kept below 1%. Average relative response factors were used in quantitation. Quantitation of total toxaphene employed the sum of all detectable (S/N > or = 3) 6-C1 to 10-Cl homolog peak areas, while the individual congeners were quantified followed the standard procedures for single analytes. Multi-point calibration solutions ranged from 0. 5 (5 for P62) to 500 microg/L for the individual congeners, and 50 to 500 microg/L for technical toxaphene, with the lowest calibration levels as lower limits of quantitation. Average congener recovery was (90.8 +/- 17.4)% (n =10) in spiked sediment with relative standard deviations of 5.4% - 12.8% (n =10), underscoring an excellently accurate and

  18. An invasive plant alters pollinator-mediated phenotypic selection on a native congener.

    Science.gov (United States)

    Beans, Carolyn M; Roach, Deborah A

    2015-01-01

    • Recent studies suggest that invasive plants compete reproductively with native plants by reducing the quantity or quality of pollinator visits. Although these studies have revealed ecological consequences of pollinator-mediated competition between invasive and native plants, the evolutionary outcomes of these interactions remain largely unexplored.• We studied the ecological and evolutionary impact of pollinator-mediated competition with an invasive jewelweed, Impatiens glandulifera, on a co-occurring native congener, I. capensis. Using a pollinator choice experiment, a hand pollination experiment, and a selection analysis, we addressed the following questions: (1) Do native pollinators show preference for the invasive or native jewelweed, and do they move between the two species? (2) Does invasive jewelweed pollen inhibit seed production in the native plant? (3) Does the invasive jewelweed alter phenotypic selection on the native plant's floral traits?• The pollinator choice experiment showed that pollinators strongly preferred the invasive jewelweed. The hand pollination experiment demonstrated that invasive pollen inhibited seed production in the native plant. The selection analysis showed that the presence of the invasive jewelweed altered phenotypic selection on corolla height in the native plant.• Invasive plants have the potential to alter phenotypic selection on floral traits in native plant populations. If native plants can evolve in response to this altered selection pressure, the evolution of floral traits may play an important role in permitting long-term coexistence of native and invasive plants. © 2015 Botanical Society of America, Inc.

  19. Hybridization and reproductive isolation between diploid Erythronium mesochoreum and its tetraploid congener E. albidum (Liliaceae).

    Science.gov (United States)

    Roccaforte, Kathy; Russo, Sabrina E; Pilson, Diana

    2015-06-01

    Polyploidy has played an important role in angiosperm diversification, but how polyploidy contributes to reproductive isolation remains poorly understood. Most work has focused on postzygotic reproductive barriers, and the influence of ploidy differences on prezygotic barriers is understudied. To address these gaps, we quantified hybrid occurrence, interspecific self-compatibility differences, and the contributions of multiple pre- and postzygotic barriers to reproductive isolation between diploid Erythronium mesochoreum (Liliaceae) and its tetraploid congener Erythronium albidum. Reproductive isolation between the study species was nearly complete, and naturally occurring hybrids were infrequent and largely sterile. Although postzygotic barriers effected substantial reproductive isolation when considered in isolation, the study species' spatial distributions and pollinator assemblages overlapped little, such that interspecific pollen transfer is likely uncommon. We did not find evidence that E. albidum and E. mesochoreum differed in mating systems, indicating that self-incompatibility release may not have fostered speciation in this system. Ultimately, we demonstrate that E. albidum and E. mesochoreum are reproductively isolated by multiple, hierarchically-operating barriers, and we add to the currently limited number of studies demonstrating that early acting barriers such as pollinator-mediated isolation can be important for effecting and sustaining reproductive isolation in diploid-polyploid systems.

  20. Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans.

    Science.gov (United States)

    Ahmad, Aijaz; Wani, Mohmmad Younus; Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

    2015-01-01

    We previously reported the antifungal properties of a monoterpene phenol "Eugenol" against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1-62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2-9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs.

  1. Holographic quantitative structure-activity relationship for prediction of the toxicity of polybrominated diphenyl ether congeners

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Polybrominated diphenyl ether congeners (PBDEs) might activate the AhR (aromatic hydrocarbon receptor) signal transduction,and thus might have an adverse effect on the health of humans and wildlife. Because of the limited experimental data,it is important and necessary to develop structure-based models for prediction of the toxicity of the compounds. In this study,a new molecular structure representation,molecular hologram,was employed to investigate the quantitative relationship between toxicity and molecular structures for 18 PBDEs. The model with the significant correlation and robustness (r2 = 0.991,q2LOO = 0.917) was developed. To verify the robustness and prediction capacity of the derived model,14 PBDEs were randomly selected from the database as the training set,while the rest were used as the test set. The results generated under the same modeling conditions as the optimal model are as follows:r2 = 0.988,q2LOO = 0.598,r2pred = 0.955,and RMSE (root-mean-square of errors) = 0.155,suggesting the excellent ability of the derived model to predict the toxicity of PBDEs. Furthermore,the structural features and molecular mechanism related to the toxicity of PBDEs were explored using HQSAR color coding.

  2. The hemodynamic effects of ibopamine, a dopamine congener, in patients with congestive heart failure.

    Science.gov (United States)

    Leier, C V; Ren, J H; Huss, P; Unverferth, D V

    1986-01-01

    Ten patients with congestive heart failure underwent noninvasive and invasive hemodynamic testing before and sequentially after the administration of ibopamine to determine the cardiovascular effects of this oral dopamine congener. Single doses of 200, 400 and 600 mg were administered to all patients and 5 repeated doses of 200 or 400 mg were studied in 8. Hemodynamic effects occurred as early as 30 minutes and lasted up to 4 hours after dosing. In general, ibopamine elicited statistically significant dose-related increases in cardiac output and reductions in the derived resistance of the systemic and pulmonary circulations. A biphasic response in central and peripheral pressures was observed; up to 1 hour after administration, ibopamine elevated mean right and left atrial pressures and pulmonary and systemic arterial pressures with a significant reduction of these measurements beyond 1 hour. It did not alter heart rate. Repeated doses qualitatively affected hemodynamics similar to the initial dose and did not appear to be accompanied by short-term tolerance. While oral ibopamine elicits some favorable hemodynamic effects in humans with cardiac failure, the biphasic hemodynamic response is generally undesirable in the majority of these patients.

  3. The ACE inhibitors enalapril and captopril modulate cytokine responses in Balb/c and C57Bl/6 normal mice and increase CD4(+)CD103(+)CD25(negative) splenic T cell numbers.

    Science.gov (United States)

    Albuquerque, Deijanira; Nihei, Jorge; Cardillo, Fabíola; Singh, Ram

    2010-01-01

    Increasing evidence implies beneficial effects of angiotensin-converting enzyme (ACE) inhibitors beyond those of their original indications to control hypertension. One of the most attractive non-hemodynamic properties of ACE inhibitors is their ability to regulate cytokine production. The mechanism(s) underlying the role of ACE inhibitors on cytokine synthesis are not well understood but they have traditionally been attributed to the inhibition of angiotensin (Ang) II formation. In fact, it has been extensively demonstrated that ACE inhibitors decrease Ang II-induced production of proinflammatory cytokines and chemokines. However, it is not well described if inhibition of endogenous Ang II generation by ACE inhibitors modulates systemic cytokine production in mice. To verify that, in this work, we investigated the effects of treatment with the ACE inhibitors enalapril and captopril on cytokine synthesis in C57Bl/6 and Balb/c mice. Our results show that enalapril up regulates IL-10 produced by splenocytes from Balb/c and C57Bl/6 mice and captopril increased it only in Balb/c mice. Furthermore, CD4(+)CD103(+) presented increased IL-10 production after enalapril treatment. Enalapril as well as captopril short-term treatment enhanced IL-2 synthesis in Balb/c mice. Besides, enhanced IL-2 and IL-10 levels correlates with increased CD4(+)CD103(+)CD25(negative) T cells numbers in spleens from enalapril-treated mice.

  4. Congener specific determination of toxaphene residues in fish liver oil using gas chromatography coupled to ion trap MS/MS.

    Science.gov (United States)

    Bernardo, F J Guzmán; Fernández, M A; González, M J

    2005-10-01

    A new approach to the determination of six toxaphene congeners in edible stuff has been accomplished. The analytical procedure presented in this paper involves a single-step cleanup process prior to the analysis. A solution containing three (13)C labelled polychlorinated biphenyls was used as internal standard and tetrachloronaphtalene was used as injection standard. The analytical technique used was gas chromatography coupled to ion trap mass spectrometry detector in MS/MS mode. The parameters affecting the successive fragmentations were discussed and optimized. The limits of detection ranged from 2 to 49pg microl(-1). The toxaphene congeners were determined in two different fish liver oil pills sold in Spain as a supplementary vitamin support.

  5. Determining indicator toxaphene congeners in soil using comprehensive two-dimensional gas chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Zhu, Shuai; Gao, Lirong; Zheng, Minghui; Liu, Huimin; Zhang, Bing; Liu, Lidan; Wang, Yiwen

    2014-01-01

    Toxaphene, which is a broad spectrum chlorinated pesticide, is a complex mixture of several hundred congeners, mainly polychlorinated bornanes. Quantifying toxaphene in environmental samples is difficult because of its complexity, and because each congener has a different response factor. Toxaphene chromatograms acquired using one-dimensional gas chromatography (1DGC) show that this technique cannot be used to separate all of the toxaphene congeners. We developed and validated a sensitive and quantitative method for determining three indicator toxaphene congeners in soil using an isotope dilution/comprehensive two-dimensional gas chromatography-tandem mass spectrometry (GC × GC-MS). The samples were extracted using accelerated solvent extraction, and then the extracts were purified using silica gel columns. (13)C₁₀-labeled Parlar 26 and 50 were used as internal standards and (13)C₁₀-labeled Parlar 62 was used as an injection standard. The sample extraction and purification treatments and the GC × GC-MS parameters were optimized. Subsequently the samples were determined by GC × GC-MS. The limits of detection for Parlar 26, 50, and 62 were 0.6 pg/g, 0.4 pg/g, and 1.0 pg/g (S/N=3), respectively, and the calibration curves had good linear correlations between 50 and 1000 μg/L (r(2)>0.99). Comprehensive two-dimensional GC gave substantial improvements over one-dimensional GC in the toxaphene analysis. We analyzed soil samples containing trace quantities of toxaphene to demonstrate that the developed method could be used to analyze toxaphene in environmental samples.

  6. A divergent approach to the synthesis of simplexides and congeners via a late-stage olefin cross-metathesis reaction.

    Science.gov (United States)

    Li, Jiakun; Li, Wei; Yu, Biao

    2013-08-14

    Simplexides constitute a unique group of immunosuppressive glycolipids that demonstrate antiproliferative activities against activated T-cell lymphocytes via a unique non-cytotoxic inhibition. To investigate the structure-activity relationship of the varied long-chain secondary alcohols on simplexides, we developed an efficient and divergent route to the synthesis of simplexides and congeners, taking advantage of a late-stage olefin cross-metathesis reaction.

  7. Predicting the Congener-Specific Environmental Behaviour of Perfluorinated Acid Contaminants Using Semi-Empirical Computational Methods

    OpenAIRE

    Sierra Rayne; Kaya Forest; Ken J. Friesen

    2008-01-01

    Perfluorinated acids (PFAs) are contaminants detected worldwide in a range of abiotic and biotic environmental matrices. The two major classes of PFAs include the perfluorinated carboxylic acids (PFCAs) and perfluorinated sulfonic acids (PFSAs), both of which are considered persistent and potentially bioaccumulative. Current research and regulatory efforts are focussed on the straight-chain members of each PFA class and homologue group, primarily because these congeners are the major componen...

  8. Seasonal variability of polychlorinated biphenyls (PCBs) and polychlorinated diphenyl ethers (PBDEs) congener profiles in butter in Poland: dietary risk evaluation.

    Science.gov (United States)

    Roszko, Marek; Szymczyk, Krystyna; Rzepkowska, Małgorzata; Jędrzejczak, Renata

    2014-01-01

    Various statistical methods have been employed to analyse in details seasonal diversification of polychlorinated biphenyl (PCB)/polybrominated diphenyl ether (PBDE) congener profiles found in butter fat. The variability of the PCB/PBDE congener profiles indicates the presence of various sources of the milk fat contamination. The obtained results suggest that the environmental chemical background has the highest share in the contamination sources pattern. Ion trap mass spectrometry coupled to high-resolution gas chromatography with semi-permeable membrane dialysis sample cleanup was used for determination of PCBs and PBDEs in milk fat. Determined butter fat PCB profiles were similar to the profiles characteristic for Aroclor 1254 technical mixture. Our data indicate that dietary intake of PCB/PBDE with milk and milk products may be estimated to be about 717.5 pg kg b.w.(-1) day(-1) for six-indicator PCBs, 0.329 (equivalent toxicity, TEQ) pg kg b.w.(-1) day(-1) for 12 DL PCBs and 50 pg kg b.w.(-1) day(-1) for PBDEs (sum of 14 congeners).

  9. Polychlorinated biphenyl source attribution in Green Bay, Wisconsin, USA, using multivariate similarity among congener profiles in sediment samples.

    Science.gov (United States)

    Cacela, Dave; Beltman, Douglas J; Lipton, Joshua

    2002-08-01

    Polychlorinated biphenyl (PCB) congener concentrations measured in 1,189 sediment samples from Green Bay (MI/WI, USA), Lake Michigan (MI/WI, USA), and the Fox River (WI, USA) were analyzed statistically to evaluate whether PCB congener profiles in outer Green Bay are more similar to those observed in inner Green Bay or Lake Michigan. Similarities among PCB profiles were assessed with complementary multivariate analysis techniques: Principal component analysis (PCA), cluster analysis, and classification trees. The PCA indicated that profiles in outer Green Bay are distinct from those of inner Green Bay or Lake Michigan but are more similar to those of inner Green Bay. The outer bay profiles are dissimilar to profiles that would result from a simple process of mixing contaminated sediments from the inner bay with Lake Michigan sediments and, therefore, support the conclusion that contaminants in outer Green Bay come from discharges of the Fox River. Several classification trees based on small sets of congener proportions defined simple rules that consistently distinguished the regional profiles. Application of these rules to classify the outer bay samples suggests that the profiles of less than 7% of outer bay samples are similar to Lake Michigan profiles. These results are interpreted with respect to physical transport and chemical weathering processes that may account for the observed differences.

  10. Isolation of pure enantiomers of Toxaphene congeners via hydrochlorination and chlorination of Pinene and composition of Soviet polychloropinene

    Energy Technology Data Exchange (ETDEWEB)

    Nikiforov, V.; Trukhin, A.; Kruchkov, F.; Kiprianova, A.; Miltsov, S. [Sankt-Peterburgskij Univ. (Russian Federation). Dept. of Chemistry; Kallenborn, R. [NILU, Kjeller (Norway)

    2004-09-15

    Toxaphene is an insecticidal mixture, produced by the controlled photochlorination of camphene1. In the USSR similar insecticide - Polychloropinene was produced by chlorination of {alpha}-pinene with AIBN (azobisisobutyronitrile) as initiator. Natural camphene occurs in different essential oils in (+)-form as well as (-)-form. Production of artificial camphene starts from natural {alpha}-pinene, which is also chiral. All noted types of camphene are used for toxaphene synthesis by different manufacturers. Some congeners in selected samples of technical Toxaphene were shown to have small deviations from racemic distribution. Nevertheless, there is no information about any enantiomerically pure congeners of toxaphene. The amount of Polychloropinene produced in the USSR is estimated to be 160 thousand tons, which is a significant contribution into the total global production. Unfortunately, there is no traceable sample of Soviet Polychloropinene available. In the present work we report on the preparation of artificial model Polychloropinene mixtures with different content of chlorine in an attempt to find the difference between Toxaphene and Soviet Polychloropinene. Another goal of our research project is to prepare pure enantiomers of important Toxaphene congeners, to establish their configuration and thus to provide more opportunities to enantiomerspecific environmental analysis of Toxaphene residues.

  11. Distribution and uptake of key polychlorinated biphenyl and polybrominated diphenyl ether congeners in benthic infauna relative to sediment organic enrichment.

    Science.gov (United States)

    Burd, Brenda J; Macdonald, Tara A; Macdonald, Robie W; Ross, Peter S

    2014-10-01

    As part of a broader study of budgets, transport, and bioaccumulation of persistent organic contaminants in the Strait of Georgia, Canada, matching samples of sediment and bulk benthos were collected near two marine sewage outfalls, two large urban harbours, and background areas. Samples were analyzed for polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) congeners. We present data for those congeners that fell within the top six rankings by concentration (23 PCBs and 10 PBDEs) within at least one of the environmental media measured in other studies (air, water, sediments, benthos, pelagic biota). Multifactor regression analyses incorporating sediment characteristics (total organic carbon, fines) predicted uptake (r (2) = 0.74 to 0.98, p supply food and sediments with PCB concentrations similar to ambient sediments. However, organic enrichment of sediments near outfalls clearly enhanced PCB uptake by benthos, probably due to greatly increased biomass turnover near these sources. Data suggest there to be an initial reservoir of PCBs in newly settled juvenile benthos, which is much less evident for PBDEs. This is likely a consequence of the ecosystem-wide distribution of legacy PCBs but not the more current-use PBDEs. Congener-uptake patterns were dependent on source and input dynamics, feeding methods, and contaminant metabolism or debromination, particularly of deca-BDE.

  12. MPD in Telomerase Null Mice

    Science.gov (United States)

    2007-09-01

    telomere dysfunctional mice will further fuel the genomic instability generated from progressive Figure 5 5FU treated telomere dysfunction bone...marrow has increased megakaryocytic colonies. Equal number of bone marrow cells from the 5FU treated mice of the various indicated cohorts are...We treated the cohorts of the G4 mTerc mutant mice with telomere dysfunction and normal G0 controls with 5FU at (50mg/kg body weight) once every

  13. Distribution and congener profiles of short-chain chlorinated paraffins in indoor/outdoor glass window surface films and their film-air partitioning in Beijing, China.

    Science.gov (United States)

    Gao, Wei; Wu, Jing; Wang, Yawei; Jiang, Guibin

    2016-02-01

    Short-chain chlorinated paraffins (SCCPs) are a group of n-alkanes with carbon chain length of 10-13. In this work, paired indoor/outdoor samples of organic films on window glass surfaces from urban buildings in Beijing, China, were collected to measure the concentrations and congener distributions of SCCPs. The total SCCP levels ranged from 337 ng/m(2) to 114 μg/m(2), with total organic carbon (TOC) normalized concentrations of 365 μg/m(2)-365 mg/m(2). Overall, the concentrations of SCCPs on the interior films were higher than the concentrations on the exterior films, suggesting an important indoor environmental exposure of SCCPs to the general public. A significant linear relationship was found between the SCCP concentrations and TOC, with a correlation coefficient of R = 0.34 (p < 0.01). A film-air partitioning model suggests that the indoor gas-phase SCCPs are related to their corresponding window film levels.

  14. Phthalate esters and childhood asthma: A systematic review and congener-specific meta-analysis.

    Science.gov (United States)

    Li, Ming-Chieh; Chen, Chi-Hsien; Guo, Yue Leon

    2017-10-01

    Exposure to phthalate esters (PAEs) has been associated with childhood asthma, but the congener-specific effects of PAEs on childhood asthma were unclear. We aimed to systematically review and meta-analyze observational studies on the associations between specific effects of PAEs and the risk of childhood asthma. Relevant studies were identified by searching three databases up to October 20, 2016. The reference lists of the retrieved articles were also reviewed. We included observational studies that reported risk estimates with 95% confidence intervals (CIs) for the associations between phthalate exposure and the risk of childhood asthma. Fixed-effects models were generally applied to calculate pooled risk estimates. When heterogeneity was present, random-effects models were applied. A total of nine studies featuring 43 data points were included in our final meta-analyses. Results indicated that the benzyl butyl phthalate (BBzP) exposure had a significant association with the risk of childhood asthma. The Odd Ratios (ORs) were from 1.39 to 1.41 for different combination strategies. Subgroup analyses by different exposure period or samples used showed that prenatal exposure to BBzP had a stronger association with the risk of childhood asthma (OR = 1.38, 95% CI = 1.09-1.75), compared to those with postnatal exposure. Besides, the association was evident when the phthalate exposure was measured from dust samples. The OR for the associations between di-2-ethylhexyl phthalate (DEHP) in dust and childhood asthma was 2.71 (95% CI = 1.39-5.28), and 2.08 (95% CI = 1.10-3.92) for BBzP. Our study suggested a positive association between DEHP and BBzP exposure and childhood asthma. Future studies are warranted to identify the underlying mechanisms of the association. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Anti-plasmodial and anti-leishmanial activity of conformationally restricted pentamidine congeners.

    Science.gov (United States)

    Huang, Tien L; Vanden Eynde, Jean Jacques; Mayence, Annie; Donkor, Isaac O; Khan, Shabana I; Tekwani, Babu L

    2006-08-01

    A library of 52 pentamidine congeners in which the flexible pentyldioxy linker in pentamidine was replaced with various restricted linkers was tested for in-vitro activity against two Plasmodium falciparum strains and Leishmania donovani. The tested compounds were generally more effective against P. falciparum than L. donovani. The most active compounds against the chloroquine-sensitive (D6, Sierra Leone) and -resistant (W2, Indochina) strains of P. falciparum were bisbenzamidines linked with a 1,4-piperazinediyl or 1, 4-homopiperazinediyl moiety, with IC50 values (50% inhibitory concentration, inhibiting parasite growth by 50% in relation to drug-free control) as low as 7 nM based on the parasite lactate dehydrogenase assay. Seven piperazine-linked bisbenzamidines substituted at the amidinium nitrogens with a linear alkyl group of 3-6 carbons (22, 25, 27, 31) or cycloalkyl group of 4, 6 or 7 carbons (26, 32, 34) were more potent (IC50pentamidine as anti-plasmodial agents. The most active anti-leishmanial agents were 4,4'-[1,4-phenylenebis(methyleneoxy)]bisbenzenecarboximidamide (2, IC50 approximately 0.290 microM) and 1,4-bis[4-(1H-benzimidazol-2-yl)phenyl] piperazine (44, IC50 approximately 0.410 microM), which were 10- and 7-fold more potent than pentamidine (IC50 approximately 2.90 microM). Several of the more active anti-plasmodial agents (e.g. 2, 31, 33, 36-38) were also potent anti-leishmanial agents, indicating broad antiprotozoal properties. However, a number of analogues that showed potent anti-plasmodial activity (1, 18, 21, 22, 25-28, 32, 43, 45) were not significantly active against the Leishmania parasite. This indicates differential modes of anti-plasmodial and anti-leishmanial actions for this class of compounds. These compounds provide important structure-activity relationship data for the design of improved chemotherapeutic agents against parasitic infections.

  16. RC-160的碘標方法比較及其生物分布特征%Comparison radioiodination methods of RC-160 and its biodistribution in normal mice

    Institute of Scientific and Technical Information of China (English)

    汪静; 王喜青; 王連剛; 李富軍

    2002-01-01

    目的擬建立一種高效碘標多肽RC-160的方法.方法以溴代琥珀酰亞胺(NBS) 為氧化劑,常規氯胺T法作為對照,對125I-RC-160的標記率、比活度進行評價,并觀察125I-RC-160在正常小鼠體内的生物分布特征.結果在丙酮:生理鹽水=1:1體系中,測得125I-RC-160的標記率NBS法為92%,比放射性為1.75×1012Bq/mmoL,標記率隨NBS用量增加而增高,最佳用量比為RC-160(μg):125I(MBq):NBS(μg)=3:7.4:1,且產物無需純化;Ch-T法標記率為56%.,比放射性為0.65×1012Bq/mmoL,經SepPaK-C18反向色譜柱純化,125I-RC-160的放射化學純度>98%.標記物在血中清除較快,注射后不到1小時血中的放射性就下降了87.2%;125I-RC-160在腎内濃集度很低,主要經過消化系統排出體外.結論NBS法可高效碘標多肽,標記后無需純化,减少了對操作者的輻射,是一種碘標的理想方法.%Objective We aims to establish a method of labeling of RC-160 with 125I. Methods NBS was used as oxi dant. Ch-T method was also performed as control. Labeling yield and specific activity of 125I-RC-160 were determined.Biodistribution of 125 I-RC-160 in normal mice was observed. Results When using acetone and saline (1: 1) as developer,labeling yield and specific radioactivity of 125 I-RC-160 was 92% and 1.75 × 10 12 Bq/mmol respectively with NBS method.The labeling yield was raised with the increase of NBS dose. The optimal dose of RC-160 (g): 125I (MBq): NBS (g)was 3: 7.4: 1. The 125 I-RC-160 prepared with NBS method needed no purification. Labeling yield and specific radioac tivity of 125I-RC-160 was 56% and 0. 65 1012 Bq/mmol respectively with Ch-T method. Reverse-phase (RP) chromatog raphy was used to purify the products. Radiochemical purity of 125I-RC-160 was over 98% with Ch-T method. Radioactiv-ity of 125 I-RC-160 in blood was decreased by 87.2% within less than 1 hr, which indicated that a substantial amount of the injected dose had been cleared from blood. Very little

  17. 188Re直接法标记CD45单抗及其体内生物分布研究%Direct-radiolabeling of CD45 monoclonal antibody with rhenium-188 and its biodistribution in normal mice

    Institute of Scientific and Technical Information of China (English)

    郑文莉; 李贵平; 黄宝丹; 杜丽; 黄凯

    2013-01-01

    Objective With direct-labeling method of CD45 McAb with 188Re, to investigate its bio-distribution character in normal mice. Methods The disulfide bond in the molecule of CD45 monoclonal antibody was reduced to form a mercapto group by the mercaptoethanol (2-ME). The labeling was conducted by stannous chloride used as reductant of 188Re, and sodium glucoheptonate as intermediate.weak ligands, then 188Re was directly labeled CD45 mAb alone; The reaction mixture was separated and purified throuth the PD-10 column;Labeling efficiency and radiochemical purity were measured by the paper chromatography. Then stability of 188Re labeled CD45 McAb was determined in vitro. The biodistribution in the healthy Kunming mice after intravenous injection of 188Re-CD45 McAb was determined. Results The labeling efficiency of 188Re-CD45 McAb was (85.25±2.63)%, and radiochemical purity was (92.54±3.56)%. The specific activity was (2.06±0.07) TBq/mmol;The radiochemical purity of 188Re-CD45 McAb was (64.33±1.53)% after incubating 24 h in room temperature. While mixed the saline and healthy rat serum at 37℃for 24 h, the radiochemical purity was (64. 2±3. 77)%and(56. 7±4. 16)%, respectively. The biodistribution result showed that the radioactivity in body was mainly distributed in kidney and liver, followed by lung, bone and blood. Conclusion The method of direct-labeling CD45 McAb with 188Re is not only simple, but also has high labeling efficiency. 188Re-CD45 McAb has good stability in vitro. After injected intravenously, radioactive label is mainly excreted through kidneys with a higher accumulation in liver, and it accords with the in vivo kinetics characteristic of labeled antibody.%目的:利用188Re直接法标记CD45单抗,探讨其在正常小鼠体内的生物学分布特性。方法应用2-巯基乙醇(2-ME)还原CD45单抗分子中的二硫键形成巯基;以氯化亚锡作为188Re的还原剂,葡庚糖酸钠为中间弱配体,188Re直接标记CD45

  18. Microcystin congeners contribute to toxicity in the halophilic cyanobacterium Aphanothece halophytica

    Directory of Open Access Journals (Sweden)

    Vishwakarma Rashi

    2014-01-01

    Full Text Available Aphanothece halophytica is an extremely saline cyanobacterium. This study investigates the toxic nature of the organism and presents the first report of hepatotoxic cyclic heptapeptide microcystin analogs. The activity of the crude extract was investigated in mice. Results showed acute toxicity with mice death at about 4 h. Histopathological examination indicated massive alveolar hemorrhage and extensive congestion in liver cells. Increases in the levels of serum enzymes, i.e., AST (aspartate aminotransferase, ALT (alanine aminotransferase and LDH (lactate dehydrogenase, provide further evidence of cell injury. An ELISA-based immunological detection kit confirmed the presence of microcystin analogs.

  19. Restoration of high-density lipoprotein levels by cholesteryl ester transfer protein expression in scavenger receptor class B type I (SR-BI) knockout mice does not normalize pathologies associated with SR-BI deficiency

    NARCIS (Netherlands)

    Hildebrand, Reeni B; Lammers, Bart; Meurs, Illiana; Korporaal, Suzanne J A; De Haan, Willeke; Zhao, Ying; Kruijt, J Kar; Praticò, Domenico; Schimmel, Alinda W M; Holleboom, Adriaan G; Hoekstra, Menno; Kuivenhoven, Jan Albert; Van Berkel, Theo J C; Rensen, Patrick C N; Van Eck, Miranda

    OBJECTIVE: Disruption of scavenger receptor class B type I (SR-BI) in mice impairs high-density lipoprotein (HDL)-cholesterol (HDL-C) delivery to the liver and induces susceptibility to atherosclerosis. In this study, it was investigated whether introduction of cholesteryl ester transfer protein

  20. Congener-specific analysis of non-dioxin-like polychlorinated biphenyls in blood collected from 195 pregnant women in Sapporo City, Japan.

    Science.gov (United States)

    Todaka, Takashi; Hori, Tsuguhide; Hirakawa, Hironori; Kajiwara, Jumboku; Yasutake, Daisuke; Onozuka, Daisuke; Kato, Shizue; Sasaki, Seiko; Nakajima, Sonomi; Saijo, Yasuaki; Sata, Fumihiro; Kishi, Reiko; Iida, Takao; Furue, Masutaka

    2008-10-01

    We conducted a congener-specific analysis of non-dioxin-like polychlorinated biphenyls (non-dioxin-like PCBs) in blood collected between July 2002 and July 2004 from 195 pregnant women living in Sapporo City of Hokkaido Prefecture, Japan. The present study is one of the few studies in which full congener concentrations of non-dioxin-like PCBs have been measured in the blood of pregnant women. Of the 195 pregnant women, 101 were primipara (mean: 28.8 years, median: 28.0 years) and 94 were multipara (mean: 32.3 years, median: 33.0 years). Among the 197 non-dioxin-like PCB congeners, 58 congeners were identified in the blood of pregnant women. The arithmetic mean total concentrations of 58 non-dioxin-like PCB congeners in the blood of primiparous and multiparous mothers in Sapporo City were 42.2-329.3 (mean: 114.5, median: 98.6) and 31.5-258.0 (mean: 100.3, median: 91.4)ngg(-1)lipid, respectively. The results show that the contamination of non-dioxin-like PCBs in the blood of women has decreased compared to past levels in other domestic areas, in which the subject age was similar to that in this study. The results of the present study indicate that current levels of non-dioxin-like PCBs in the blood of Japanese women and can be used as baseline data for future temporal trends. The sums of the ratios of the concentrations of hexaCBs and heptaCBs to the total concentrations of 58 non-dioxin-like PCB congeners in the blood of primiparous and multiparous mothers were 78.5% and 77.7%, respectively. The hexaCBs ratios in the blood of primiparous and multiparous mothers were 45.4% and 44.7%, respectively. HexaCB-153 among hexaCBs congeners, the most abundant congener in the blood of primiparous and multiparous mothers, contributed approximately 22.0% and 21.8% to the total concentrations of 58 non-dioxin-like PCBs congeners that were measured in the blood, respectively. Among the non-dioxin-like PCB congeners measured in the present study, hexaCB-138, heptaCB-170, hepta

  1. Comparative metabolism, covalent binding and toxicity of BHT congeners in rat liver slices.

    Science.gov (United States)

    Reed, M; Fujiwara, H; Thompson, D C

    2001-11-28

    The metabolism, covalent binding and hepatotoxicity of butylated hydroxytoluene (BHT, 4-methyl-2,6-di-t-butylphenol) and two congeners (E-BHT, 4-ethyl-2,6-di-t-butylphenol; I-BHT, 4-isopropyl-2,6-di-t-butylphenol) were compared using precision-cut liver slices prepared from phenobarbital (PB)-treated male Sprague-Dawley rats. At equimolar concentrations (1 mM) BHT was the most toxic of the three compounds, causing an 80% decrease in cell viability over a 6 h incubation period. E-BHT was intermediate in toxicity while the isopropyl derivative was relatively nontoxic. Intracellular glutathione levels decreased prior to the onset of cytotoxicity. The cytochrome P450 inhibitor metyrapone completely inhibited the toxicity of all three compounds. The rates of metabolism of the three compounds to glutathione conjugates were compared in both PB-treated microsomes and PB-induced liver slices. In both models, the rate of formation was greatest for BHT, followed by E-BHT and I-BHT. Synthetic quinone methides (QMs) were prepared from each parent phenol and the rates of reactivity with three nucleophiles (water, methanol and glutathione) were compared. With each nucleophile, BHTQM was the most reactive, while I-BHTQM was the least reactive. Finally, covalent binding to protein was assessed in two ways. First, alkylation of an isolated model protein (bovine insulin) was measured in a microsomal enzyme activation system by mass spectrometry. Incubations with BHT produced the greatest extent of protein alkylation, followed by E-BHT, while no alkylation was observed with I-BHT. In the second system, covalent binding to cellular protein was assessed in rat liver PB microsomes and tissue slices by Western blotting using an antibody specific for the tert-butylphenol portion of the compounds. Binding was greatest for BHT, intermediate for E-BHT and could not be detected for I-BHT. The alkylation pattern for E-BHT was strikingly similar to that of BHT, suggesting that both compounds

  2. Coronaridine congeners inhibit human α3β4 nicotinic acetylcholine receptors by interacting with luminal and non-luminal sites.

    Science.gov (United States)

    Arias, Hugo R; Targowska-Duda, Katarzyna M; Feuerbach, Dominik; Jozwiak, Krzysztof

    2015-08-01

    To characterize the interaction of coronaridine congeners with human (h) α3β4 nicotinic acetylcholine receptors (AChRs), structural and functional approaches were used. The Ca(2+) influx results established that coronaridine congeners noncompetitively inhibit hα3β4 AChRs with the following potency (IC50's in μM) sequence: (-)-ibogamine (0.62±0.23)∼(+)-catharanthine (0.68±0.10)>(-)-ibogaine (0.95±0.10)>(±)-18-methoxycoronaridine [(±)-18-MC] (1.47±0.21)>(-)-voacangine (2.28±0.33)>(±)-18-methylaminocoronaridine (2.62±0.57 μM)∼(±)-18-hydroxycoronaridine (2.81±0.54)>(-)-noribogaine (6.82±0.78). A good linear correlation (r(2)=0.771) between the calculated IC50 values and their polar surface area was found, suggesting that this is an important structural feature for its activity. The radioligand competition results indicate that (±)-18-MC and (-)-ibogaine partially inhibit [(3)H]imipramine binding by an allosteric mechanism. Molecular docking, molecular dynamics, and in silico mutation results suggest that protonated (-)-18-MC binds to luminal [i.e., β4-Phe255 (phenylalanine/valine ring; position 13'), and α3-Leu250 and β4-Leu251 (leucine ring; position 9')], non-luminal, and intersubunit sites. The pharmacophore model suggests that nitrogens from the ibogamine core as well as methylamino, hydroxyl, and methoxyl moieties at position 18 form hydrogen bonds. Collectively our data indicate that coronaridine congeners inhibit hα3β4 AChRs by blocking the ion channel's lumen and probably by additional negative allosteric mechanisms by interacting with a series of non-luminal sites.

  3. Comparison of congener profiles of polychlorinated biphenyls between Yu-cheng children and a potential food source

    Energy Technology Data Exchange (ETDEWEB)

    Lung Shih-Chun Candice [Research Center for Environmental Changes, Academia Sinica, Taipei (Taiwan); Guo Yu-Liang Leon; Chang Ho-Yuan [Dept. of Environmental and Occupational Health, Coll. of Medicine, National Cheng Kung Univ., Tainan (Taiwan)

    2004-09-15

    In 1979, about two thousand people in central Taiwan were intoxicated by consumption of the rice oil that was contaminated with polychlorinated biphenyls (PCBs). This ''Yu-cheng'' incident was one of the two human tragedies which people ingested substantial amounts of PCBs within a short period of time. Some of the follow-up epidemiological studies focused on the children born to the exposed mothers, the Yu-cheng children, since they could be exposed to PCBs via breast-feeding or transplacental transfer. This report presents the results of the serum PCB levels of the 21 Yu-cheng children with a congener-specific analysis. On the other hand, fish consumption is thought to be the single most important exposure route to PCBs to the general public; thus, it is crucial to understand PCB exposure from fish consumption. In a separated study to assess PCB contamination in fish, PCB congener concentrations in tilapia (Oreochromis hybrids), the most popular fish in Taiwan, were evaluated. The consumption quantity of tilapia is the highest throughout the Island. It is mostly farmed in fresh water but can also be bred in saltwater. This report presents the concentrations and profiles in the serums of the Yu-cheng children. The congener profile is compared with PCB profile in the serum of Yu-cheng women reported previously and that in one of the potentially significant exposure source, tilapia, conducted in a separated work. Remarkable similarity between the profile of Yu-cheng children and that of the tilapia is revealed and discussed.

  4. Sex, BMI and age in addition to dietary intakes influence blood concentrations and congener profiles of dioxins and PCBs.

    Science.gov (United States)

    Knutsen, Helle K; Kvalem, Helen E; Haugen, Margaretha; Meltzer, Helle M; Brantsaeter, Anne L; Alexander, Jan; Päpke, Olaf; Liane, Veronica H; Becher, Georg; Thomsen, Cathrine

    2011-05-01

    The aim of this study was to i) characterize dietary polychlorinated biphenyls (PCBs) and dioxin exposure in consumers of fish from the PCB contaminated Lake Mjøsa in Norway ii) examine the influence of demographic factors on blood concentrations and congener composition of dioxins and PCBs, iii) characterize dietary sources and possible exposures above tolerable intake. Blood samples were analysed for dioxin-like (dl) compounds (PCDD/Fs and dl-PCBs) and non-dl-PCBs (ndl-PCBs). Dietary exposures were calculated using food frequency questionnaires (n=64). Men had higher median intake of dl-compounds than women (1.2 and 0.85 pg TEQ/kg bw/day), but similar blood concentrations (23.3 and 25.8, pg TEQ/g lipid weight (lw)). For non-dl-PCBs, intakes (6.5 and 4.5 ng/kg bw/day) and blood concentrations (381 and 224 ng/g lw) were higher in men than in women. Blood concentrations correlated with dietary intakes in men only. Increasing BMI and age elevated blood concentrations mainly in women. Men and women had different blood congener profiles, with a higher share of PCB-126 in women, despite similar dietary congener profiles. Eleven participants exceeded the tolerable intake for dl-compounds. Fish from Lake Mjøsa was the main dietary source. The higher influence of BMI and age for women than for men may have implications for risk assessment. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Gradient HPLC separation of dehydroepiandrosterone (DHEA) from its metabolites and biological congeners: role of tetrahydrofuran in the chromatographic mechanism.

    Science.gov (United States)

    Gergely, András; Horváth, Péter; Szász, György; Veress, Gábor

    2009-08-01

    A three-step gradient reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for the separation of dehydroepiandrosterone (DHEA), its sulfate ester (DHEA-S), its three C7-oxidized metabolites (7alphaOH-DHEA, 7betaOH-DHEA, 7-keto-DHEA), and its biosynthetic congeners (androstenedione, testosterone, estradiol, pregnenolone). This new method allows the quantitative characterization of DHEA metabolism and biosynthetic transformation under given physiological, pathological, or therapeutically influenced circumstances. Tetrahydrofuran probably acts as a proton acceptor coadsorbent, while isopropanol behaves as a proton donor during the separation of testosterone, estradiol, and the stereoisomers of 7-OH-DHEA.

  6. Isolation of a Genomic Region Affecting Most Components of Metabolic Syndrome in a Chromosome-16 Congenic Rat Model.

    Directory of Open Access Journals (Sweden)

    Lucie Šedová

    Full Text Available Metabolic syndrome is a highly prevalent human disease with substantial genomic and environmental components. Previous studies indicate the presence of significant genetic determinants of several features of metabolic syndrome on rat chromosome 16 (RNO16 and the syntenic regions of human genome. We derived the SHR.BN16 congenic strain by introgression of a limited RNO16 region from the Brown Norway congenic strain (BN-Lx into the genomic background of the spontaneously hypertensive rat (SHR strain. We compared the morphometric, metabolic, and hemodynamic profiles of adult male SHR and SHR.BN16 rats. We also compared in silico the DNA sequences for the differential segment in the BN-Lx and SHR parental strains. SHR.BN16 congenic rats had significantly lower weight, decreased concentrations of total triglycerides and cholesterol, and improved glucose tolerance compared with SHR rats. The concentrations of insulin, free fatty acids, and adiponectin were comparable between the two strains. SHR.BN16 rats had significantly lower systolic (18-28 mmHg difference and diastolic (10-15 mmHg difference blood pressure throughout the experiment (repeated-measures ANOVA, P < 0.001. The differential segment spans approximately 22 Mb of the telomeric part of the short arm of RNO16. The in silico analyses revealed over 1200 DNA variants between the BN-Lx and SHR genomes in the SHR.BN16 differential segment, 44 of which lead to missense mutations, and only eight of which (in Asb14, Il17rd, Itih1, Syt15, Ercc6, RGD1564958, Tmem161a, and Gatad2a genes are predicted to be damaging to the protein product. Furthermore, a number of genes within the RNO16 differential segment associated with metabolic syndrome components in human studies showed polymorphisms between SHR and BN-Lx (including Lpl, Nrg3, Pbx4, Cilp2, and Stab1. Our novel congenic rat model demonstrates that a limited genomic region on RNO16 in the SHR significantly affects many of the features of metabolic

  7. Fractionation and current time trends of PCB congeners: evolvement of distributions 1950–2010 studied using a global atmosphere-ocean general circulation model

    Directory of Open Access Journals (Sweden)

    G. Lammel

    2012-08-01

    Full Text Available PCBs are ubiquitous environmental pollutants expected to decline in abiotic environmental media in response to decreasing primary emissions since the 1970s. A coupled atmosphere-ocean general circulation model with embedded dynamic sub-models for atmospheric aerosols and the marine biogeochemistry and air-surface exchange processes with soils, vegetation and the cryosphere is used to study the transport and fate of four PCB congeners covering a range of 3–7 chlorine atoms.

    The change of the geographic distribution of the PCB mixture reflects the sources and sinks' evolvement over time. Globally, secondary emissions (re-volatilisation from surfaces are on the long term increasingly gaining importance over primary emissions. Secondary emissions are most important for the congeners with 5–6 chlorine atoms. Correspondingly, the levels of these congeners are predicted to decrease slowest. Changes in congener mixture composition (fractionation are characterized both geographically and temporally. In high latitudes enrichment of the lighter, less persistent congeners and more delayed decreasing levels in response to decreasing emissions are found. The delivery of the contaminants to high latitudes is predicted to be more efficient than previously suggested. The results suggest furthermore that the effectiveness of emission control measures may significantly vary among substances. The trends of decline of organic contaminant levels in the abiotic environmental media do not only vary with latitude (slow in high latitudes, but do also show longitudinal gradients.

  8. Congener-specific levels and patterns of polychlorinated biphenyls in edible fish tissue from the central Red Sea coast of Saudi Arabia

    KAUST Repository

    Batang, Zenon B.

    2016-08-01

    All 209 congeners of polychlorinated biphenyls (PCBs) in edible fish tissue from the central Red Sea coast (Jeddah region) of Saudi Arabia were analyzed by isotope dilution high-resolution gas chromatography–mass spectrometry. The upper-bound total PCB (ΣPCB) levels in nine commonly consumed fish species from three areas were 0.2–82.5 ng/g wet weight (17–8450 ng/g lipid weight), which were at the lower end of reported global range and far below international tolerance limits (500–3000 ng/g ww). Dioxin-like congeners contributed up to 12.8% (mean 6.5%) to ΣPCB in tissue samples, with the total PCB toxic equivalencies (TEQs) at a tolerable range (0.05–2.6 pg TEQ/g ww or 2–238 pg TEQ/g lw) for all species. PCB profiles were dominated by moderately chlorinated homologs, mainly hexachlorobiphenyls, but less chlorinated congeners were also consistently elevated, notably in Siganus rivulatus (Area III) and Mugil cephalus (Area I). It remains to be ascertained if the latter were breakdown products or due to fresh inputs. The top congeners based on dominance by both occurrence and abundance were identified as potential markers of ΣPCB in fish tissue, which can be used for future selective biomonitoring in case of reasonable constraints on full congener approach.

  9. Dietary exposure of juvenile common sole (Solea solea L.) to polybrominated diphenyl ethers (PBDEs): Part 1. Bioaccumulation and elimination kinetics of individual congeners and their debrominated metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Munschy, C., E-mail: cmunschy@ifremer.f [Institut Francais de Recherche pour l' Exploitation de la Mer (IFREMER), Laboratory of Biogeochemistry of Organic Contaminants, Rue de l' Ile d' Yeu, BP 21105, 44311 Nantes Cedex 3 (France); Heas-Moisan, K.; Tixier, C.; Olivier, N. [Institut Francais de Recherche pour l' Exploitation de la Mer (IFREMER), Laboratory of Biogeochemistry of Organic Contaminants, Rue de l' Ile d' Yeu, BP 21105, 44311 Nantes Cedex 3 (France); Gastineau, O.; Le Bayon, N.; Buchet, V. [Institut Francais de Recherche pour l' Exploitation de la Mer (IFREMER), Laboratory of Adaptation, Reproduction and Nutrition of marine fish, BP 70, 29280 Plouzane (France)

    2011-01-15

    The uptake and elimination of six PBDE congeners (BDE-28, -47, -99, -100, -153, -209) were studied in juvenile common sole (Solea solea L.) exposed to spiked contaminated food over a three-month period, then depurated over a five-month period. The results show that all of the studied PBDEs accumulate in fish tissues, including the higher brominated congener BDE-209. Several additional PBDE congeners were identified in the tissues of exposed fish, revealing PBDE transformation, mainly via debromination. The identified congeners originating from PBDE debromination include BDE-49 and BDE-202 and a series of unidentified tetra-, penta-, and hepta- BDEs. Contaminant assimilation efficiencies (AEs) were related to their hydrophobicity (log K{sub ow}) and influenced by PBDE biotransformation. Metabolism via debromination appears to be a major degradation route of PBDEs in juvenile sole in comparison to biotransformation into hydroxylated metabolites. - Juvenile sole exposed to artificially-contaminated food accumulate PBDEs, including the higher brominated congeners, and have a debromination capacity.

  10. Measurement of toxaphene congeners in pooled human serum collected in three U.S. cities using high-resolution mass spectrometry.

    Science.gov (United States)

    Barr, John R; Woolfitt, Adrian R; Maggio, Vincent L; Patterson, Donald G

    2004-05-01

    Because human toxaphene exposure data are largely lacking, we surveyed human serum pools collected from U.S. residents to determine the feasibility of measuring toxaphene in human samples and to determine whether additional analytical requirements were needed for routine measurement of toxaphene. We report a method for quantification of toxaphene congeners in human serum using a mixed-bed gradient solid-phase extraction and analysis using gas chromatography-high-resolution mass spectrometry with electron-impact ionization. In this method, we monitored low-mass fragment ions that were common to all 22 congeners. To verify the specific congeners detected, we further analyzed the extract using negative methane chemical ionization. We used this method to measure two specific congeners, Parlar 26 and 50, at concentrations ranging from about 3 to 30 pg/ml (0.7-7 ng/g lipid) in pooled human serum collected in Atlanta, Chicago, and Cincinnati. We identified several analytical parameters that must be strengthened to routinely measure toxaphene congeners in human samples.

  11. Seasonal variation of polychlorinated biphenyl congeners in surficial sediment, trapped settling material, and suspended particulate material in Lake Michigan, USA.

    Science.gov (United States)

    Robinson, Sander D; Landrum, Peter F; Van Hoof, Patricia L; Eadie, Brian J

    2008-02-01

    A unique time series of surface sediment, trapped settling material, and suspended particulate material polychlorinated biphenyl (PCB) samples were collected at a 45-m deep site off Grand Haven (MI, USA) over a 14-month period. Both concentrations and congener distributions remained constant for the sediments, although there were seasonal and interannual variability in the other matrices. Trapped settling material and suspended particulate material PCB concentrations were substantially lower (~50%) in 1997 than in the samples from December 1997 through July 1998. The cause could not be determined from the data collected, but there were some very large storms during the winter-spring period of 1998, resulting in major sediment resuspension throughout the southern basin. Observed seasonal variation in PCB concentration and congener distribution on particles likely was due to the changes in particle composition. These include particle size and the source of particles (such as the amount of resuspended sediment in trapped settling material), and the role of diagenesis of the organic matter on particles.

  12. A 25-Year Experience of Gastroenteropancreatic Neuroendocrine Tumors and Somatostatin (Congeners) Analogs: From Symptom Control to Antineoplastic Therapy.

    Science.gov (United States)

    O'Dorisio, Thomas M; Anthony, Lowell B

    2015-01-01

    Radioimmunoassay technology was utilized in the discovery of somatostatin and was quickly brought into therapeutics; however, it took the development of somatostatin congeners to solve its limitations of a short half-life. Therapeutic medical control of hyperhormonal states such as acromegaly, carcinoid syndrome and VIPoma significantly advanced from a nonspecific approach to one that specifically and effectively targeted the underlying pathophysiology. Clinical care was transformed from nonspecific symptom control to one of a significant improvement in not only quality of life, but also quantity of life. These data submitted to US and European regulatory authorities for approval included many investigative sites with no uniform protocol and multiple investigational new drugs, and have not been previously published. This review includes the original data demonstrating the transformational impact this class of agents had on specific disease subsets resulting in regulatory approval 25 years ago. Autoradiography techniques using somatostatin resulted in identifying, localizing and characterizing its receptor subtypes. Translating in vitro data to in vivo resulted in scintigraphic whole body and SPECT scans with (111)In-pentetreotide and was incorporated into standard clinical care 20 years ago. (68)Ga-octreotide congeners using PET scanning offers a major imaging advance. Peptide receptor radiotherapy has evolved over the last 2 decades and utilizes several therapeutic isotopes, including (90)Y and (177)Lu. © 2015 S. Karger AG, Basel.

  13. Investigations on the sorption of a toxaphene model congener, the B7-1450, on marine sediments.

    Science.gov (United States)

    Soubaneh, Youssouf Djibril; Lebeuf, Michel; Gouteux, Bruno; Xie, Huixiang; Nikiforov, Vladimir; Gagné, Jean-Pierre

    2008-04-01

    Sorption is a natural process that takes place in sediments or soils and changes the mobility and availability of hydrophobic organic compounds, such as toxaphene pesticide in the environment. The sorption of the 2-exo,3-endo,5-exo,8,9,10,10-heptachlorobornane (B7-1450), used as a model compound of the toxaphene heptachlorobornane congeners found in sediments, was investigated for the first time through a series of batch sorption experiments. The losses of B7-1450 due to adsorption onto glass walls and to evaporation occurring during analytical treatment steps were corrected. The study showed that these specific losses ranged from 2% to 3.5% for the glass walls adsorption and can be as high as 15% for the evaporation treatment. The sorption coefficients, K(d) and K(oc), of B7-1450 could be overestimated by >30%, particularly for low-concentration samples, if the losses were not corrected. Loss correction equations were established, validated and applied to determine sorption coefficients for the B7-1450 congener. The K(oc) values for B7-1450 determined over a gradient of concentrations ranged from 3.5x10(4) to 6.5x10(4)mlg(-1), revealing a strong affinity of B7-1450 for marine sediments.

  14. Efficacy of Marek's disease vaccines in Mhc heterozygous chickens: Mhc congenic x inbred line F1 matings.

    Science.gov (United States)

    Bacon, L D; Witter, R L

    1995-01-01

    The goal of this study is to demonstrate that Mhc (B) heterozygous chickens differ in efficacy of response to several Marek's disease (MD) vaccines. Four types of B2 heterozygotes, in addition to B2B2 homozygotes, were developed by crossing 15.B congenic males to inbred line 7(1) (B2B2) hens. The five types of F1 chicks were intermingled in isolators and vaccinated with one of four types of MD vaccine before inoculation with the very virulent Md5 strain of MD herpesvirus. The F1 chickens differ in development of protective immunity following MD vaccination from two perspectives. First, chickens of a particular Mhc genotype were protected better by some vaccines than others. Second, individual vaccine preparations protected some Mhc genotypes more effectively. We conclude that some MD vaccines are more appropriate than others for certain B-haplotypes when chickens are heterozygous for the Mhc. The value of using Mhc-congenic x inbred line F1 animals for studies concerning the influence of the Mhc on vaccinal immunity is discussed.

  15. Combined effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated biphenyls congeners in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chu, I. [Environmental Science Bureau, Ottawa (Canada); Valli, V.E. [Coll. of Veterinary Medicine, Urbana (United States)

    2004-09-15

    There has been considerable interest in conducting toxicity studies on mixtures since this approach represents realistic human exposure and would provide a better model to predict the health impacts of environmental chemicals. However, risk assessment of the chemicals is largely based on the toxicity data of individual compounds by assuming simple additive effects of these compounds. This practice has been accepted by regulatory agencies provided that the concentrations of chemicals are extremely low, and there are no interactions. The existence of interactions among the chemicals co-administered to test animals may under or over estimate the effects of a mixture if the simple additive rule is applied. Previously, we demonstrated an antagonistic effect in rats when tetrachlorodibenzo-p-dioxin (TCDD) was co-administered with polychlorinated biphenyls congeners (PCBs). The hepatic microsomal EROD, MROD and UDPGT activities of TCDD were decreased when co-administered with PCB congeners. To further explore the combined effects of these pollutants, we examined and report results on tissue residue levels of TCDD and histopathological changes in target organs of rats exposed to TCDD, PCBs and mixtures of both.

  16. 高通量测序技术研究高糖饮食对小鼠肠道菌群的影响%Comparision of intestinal microbiota in mice with normal and high-sugar diet using Miseq high-throughput sequencing

    Institute of Scientific and Technical Information of China (English)

    张芹; 周中凯; 任晓冲

    2015-01-01

    目的:比较高糖饮食和普通饲料喂养对小鼠肠道菌群的影响。方法选取16只C57BL/6J小鼠,经适应喂养1周后,随机分为正常组和高糖组,于第5周末,对小鼠粪便菌群16S rRNA的V1-V3区进行扩增, Miseq高通量测序平台测定其基因序列,与silva数据库中微生物基因序列进行比对、分类。结果研究发现:尽管差异性不显著,高糖饮食组小鼠体重和血糖值较正常饮食小鼠有明显升高;正常饮食小鼠粪便菌群多样性高于高糖饮食的小鼠;高糖组粪便中含有大量的 Firmicutes(厚壁菌门),较正常组显著升高;高糖组Bacteroidetes(拟杆菌门)数量显著低于正常组;在属的水平上,正常组和高糖组粪便菌群中含量最高的是Allobaculum,其含量无显著差异;而两组在Lactobacillus和S24-7_norank的含量上存在着显著差异。结论饮食类型对肠道菌群有着显著的影响,因而可通过调整饮食结构改善肠道菌群。%Objective To compare the composition of fecal microbiota in normal mice and high-sugar diet mice by using Miseq high-throughput sequencing technology. Methods Totally 16 C57BL/6J mice were randomly divided into 2 groups. The feces were collected after a 5-wk experimental period. The fecal bacterial composition was investigated by Miseq high-throughput sequencing of the V1-V3 region of the 16S rRNA gene compared with silva databases. Results The results showed that the body weight and blood glucose of mice with high-sugar diet were significantly increased compared to the mice fed normal diet. Bacterial diversity and richness in normal group was higher than that in high-sugar mice. In the phylum level, the relative abundance of Firmicutes was somewhat higher, while the proportion of Bacteroidetes was lower in high-sugar group compared with the normal group. In the genus level, Allobaculum was the most abundant bacterial in both groups, however, there was a significant difference in the

  17. 不同外邪对正常及免疫功能低下小鼠脾淋巴细胞增殖能力的影响%Effect of attacks factors on the immunesplenic Lymphocytes proliferation capacity of normal and low immune function mice

    Institute of Scientific and Technical Information of China (English)

    马彦平; 郭彩云; 李俊莲; 李艳彦; 杨琬芳; 李孝波; 王平; 陶功定

    2012-01-01

    Objective: To detect the proliferation capacity of splenic lymphocytes of mice in the cold, cold dampness and hot and humid environment, and discusses the effect of different factors of attacks on the immune functions of mice. Methods: We choose knife bean protein (ConA) induced spleen lymphocyte proliferation, use the MTT method to determine the spleen lymphatic proliferation capacity in mice. Results: ①The mice splenic lymphocytes proliferation capacity of all the attack factors processing groups were significantly lower than the normal group (P<0.01).②All the attack factors processing low immune functions groups compared with low immune function group, the splenic lymphocytes proliferation capacity of wind-cold, cold-dampness low immune function groups reduced significantly (P<0.01); the splenic lymphocytes proliferation capacity of dampness-heat low immune function groups decreasd, but this was not statistically significant. ③The wind-cold low immune function group compared with the wind-cold group, the cold-dampness low immune function group compared with the cold-dampness group, the dampness-heat low immune function group compared with the dampness-heat group, all the mice splenic lymphocytes proliferation capacity significantly reduced (P<0.01). Conclusion: Compared with the normal group, the mice splenic lymphocytes proliferation capacity of all the attack factor processing groups reduced, the mice splenic lymphocytes proliferation capacity of low immune modle groups especially signigicant. The study shows that the three attacks factors of wind-cold, cold-dampness, dampness-heat can make the immune function of mice reduce and cause the happen of the disease easily.%目的:通过检测在风寒、寒湿和湿热环境下小鼠脾淋巴细胞的增殖能力,探讨不同外邪因素对小鼠免疫功能的影响.方法:选择刀豆蛋白(ConA)诱导脾淋巴细胞增殖,采用MTT法测定小鼠脾淋巴细胞增殖能力.结果:①各外邪因素处理

  18. Normal Pressure Hydrocephalus (NPH)

    Science.gov (United States)

    ... your local chapter Join our online community Normal Pressure Hydrocephalus (NPH) Normal pressure hydrocephalus is a brain ... About Symptoms Diagnosis Causes & risks Treatments About Normal Pressure Hydrocephalus Normal pressure hydrocephalus occurs when excess cerebrospinal ...

  19. Congener-specific carbon isotopic analysis of technical PCB and PCN mixtures using two-dimensional gas chromatography-isotope ratio mass spectrometry.

    Science.gov (United States)

    Horii, Yuichi; Kannan, Kurunthachalam; Petrick, Gert; Gamo, Toshitaka; Falandysz, Jerzy; Yamashita, Nobuyoshi

    2005-06-01

    Analysis of stable carbon isotope fractionation is a useful method to study the sources and fate of anthropogenic organic contaminants such as polychlorinated biphenyls (PCBs) in the environment. To evaluate the utility of carbon isotopes, determination of isotopic ratios of 13C/12C in source materials, for example, technical PCB preparations, is needed. In this study, we determined delta13C values of 31 chlorobiphenyl (CB) congeners in 18 technical PCB preparations and 15 chloronaphthalene (CN) congeners in 6 polychlorinated naphthalene preparations using two-dimensional gas chromatography-combustion furnace-isotope ratio mass spectrometry (2DGC-C-IRMS). Development of 2DGC-IRMS enabled improved resolution and sensitivity of compound-specific carbon isotope analysis (CSIA) of CB or CN congeners. Delta13C values of PCB congeners ranged from -34.4 (Delors) to -22.0/1000 (Sovol). Analogous PCB preparations with similar chlorine content, but different geographical origin, had different delta13C values. PCB preparations from Eastern European countries--Delors, Sovol, Trichlorodiphenyl, and Chlorofen--had distinct delta13C values. PCB mixtures showed increased 13C depletion with increasing chlorine content. Delta13C values for individual CB congeners varied depending on the degree of chlorination in technical mixtures. Delta13C values of CN congeners in Halowaxes ranged from -26.3 to -21.7/1000 and these values are within the ranges observed for PCBs. This study establishes the range of delta13C values in technical PCB and PCN preparations, which may prove to be useful in the determination of sources of these compounds in the environment. This is the first study to employ 2DGC-IRMS analysis of delta13C values in technical PCB and PCN preparations.

  20. Transgenic overexpression of G5PR that is normally augmented in centrocytes impairs the enrichment of high-affinity antigen-specific B cells, increases peritoneal B-1a cells, and induces autoimmunity in aged female mice.

    Science.gov (United States)

    Kitabatake, Masahiro; Toda, Teppei; Kuwahara, Kazuhiko; Igarashi, Hideya; Ohtsuji, Mareki; Tsurui, Hiromichi; Hirose, Sachiko; Sakaguchi, Nobuo

    2012-08-01

    To investigate signals that control B cell selection, we examined expression of G5PR, a regulatory subunit of the serine/threonine protein phosphatase 2A, which suppresses JNK phosphorylation. G5PR is upregulated in activated B cells, in Ki67-negative centrocytes at germinal centers (GCs), and in purified B220(+)Fas(+)GL7(+) mature GC B cells following Ag immunization. G5PR rescues transformed B cells from BCR-mediated activation-induced cell death by suppression of late-phase JNK activation. In G5PR-transgenic (G5PR(Tg)) mice, G5PR overexpression leads to an augmented generation of GC B cells via an increase in non-Ag-specific B cells and a consequent reduction in the proportion of Ag-specific B cells and high-affinity Ab production after immunization with nitrophenyl-conjugated chicken γ-globulin. G5PR overexpression impaired the affinity-maturation of Ag-specific B cells, presumably by diluting the numbers of high-affinity B cells. However, aged nonimmunized female G5PR(Tg) mice showed an increase in the numbers of peritoneal B-1a cells and the generation of autoantibodies. G5PR overexpression did not affect the proliferation of B-1a and B-2 cells but rescued B-1a cells from activation-induced cell death in vitro. G5PR might play a pivotal role in B cell selection not only for B-2 cells but also for B-1 cells in peripheral lymphoid organs.

  1. Comparative gene expression profiling in two congenic mouse strains following Bordetella pertussis infection

    Directory of Open Access Journals (Sweden)

    Demant Peter

    2007-10-01

    Full Text Available Abstract Background Susceptibility to Bordetella pertussis infection varies widely. These differences can partly be explained by genetic host factors. HcB-28 mice are more resistant to B. pertussis infection than C3H mice, which could partially be ascribed to the B. pertussis susceptibility locus-1 (Bps1 on chromosome 12. The presence of C57BL/10 genome on this locus instead of C3H genome resulted in a decreased number of bacteria in the lung. To further elucidate the role of host genetic factors, in particular in the Bps1 locus, in B. pertussis infection, and to identify candidate genes within in this region, we compared expression profiles in the lungs of the C3H and HcB-28 mouse strains following B. pertussis inoculation. Twelve and a half percent of the genomes of these mice are from a different genetic background. Results Upon B. pertussis inoculation 2,353 genes were differentially expressed in the lungs of both mouse strains. Two hundred and six genes were differentially expressed between the two mouse strains, but, remarkably, none of these were up- or down-regulated upon B. pertussis infection. Of these 206 genes, 17 were located in the Bps1 region. Eight of these genes, which showed a strong difference in gene expression between the two mouse strains, map to the immunoglobulin heavy chain complex (Igh. Conclusion Gene expression changes upon B. pertussis infection are highly identical between the two mouse strains despite the differences in the course of B. pertussis infection. Because the genes that were differentially regulated between the mouse strains only showed differences in expression before infection, it appears likely that such intrinsic differences in gene regulation are involved in determining differences in susceptibility to B. pertussis infection. Alternatively, such genetic differences in susceptibility may be explained by genes that are not differentially regulated between these two mouse strains. Genes in the Igh

  2. The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations.

    Science.gov (United States)

    Meeth, Katrina; Wang, Jake Xiao; Micevic, Goran; Damsky, William; Bosenberg, Marcus W

    2016-09-01

    The remarkable success of immune therapies emphasizes the need for immune-competent cancer models. Elegant genetically engineered mouse models of a variety of cancers have been established, but their effective use is limited by cost and difficulties in rapidly generating experimental data. Some mouse cancer cell lines are transplantable to immunocompetent host mice and have been utilized extensively to study cancer immunology. Here, we describe the Yale University Mouse Melanoma (YUMM) lines, a comprehensive system of mouse melanoma cell lines that are syngeneic to C57BL/6, have well-defined human-relevant driver mutations, and are genomically stable. This will be a useful tool for the study of tumor immunology and genotype-specific cancer biology.

  3. Normalization: A Preprocessing Stage

    OpenAIRE

    Patro, S. Gopal Krishna; Sahu, Kishore Kumar

    2015-01-01

    As we know that the normalization is a pre-processing stage of any type problem statement. Especially normalization takes important role in the field of soft computing, cloud computing etc. for manipulation of data like scale down or scale up the range of data before it becomes used for further stage. There are so many normalization techniques are there namely Min-Max normalization, Z-score normalization and Decimal scaling normalization. So by referring these normalization techniques we are ...

  4. Regulation of sex determination in mice by a non-coding genomic region.

    Science.gov (United States)

    Arboleda, Valerie A; Fleming, Alice; Barseghyan, Hayk; Délot, Emmanuèle; Sinsheimer, Janet S; Vilain, Eric

    2014-07-01

    To identify novel genomic regions that regulate sex determination, we utilized the powerful C57BL/6J-Y(POS) (B6-Y(POS)) model of XY sex reversal where mice with autosomes from the B6 strain and a Y chromosome from a wild-derived strain, Mus domesticus poschiavinus (Y(POS)), show complete sex reversal. In B6-Y(POS), the presence of a 55-Mb congenic region on chromosome 11 protects from sex reversal in a dose-dependent manner. Using mouse genetic backcross designs and high-density SNP arrays, we narrowed the congenic region to a 1.62-Mb genomic region on chromosome 11 that confers 80% protection from B6-Y(POS) sex reversal when one copy is present and complete protection when two copies are present. It was previously believed that the protective congenic region originated from the 129S1/SviMJ (129) strain. However, genomic analysis revealed that this region is not derived from 129 and most likely is derived from the semi-inbred strain POSA. We show that the small 1.62-Mb congenic region that protects against B6-Y(POS) sex reversal is located within the Sox9 promoter and promotes the expression of Sox9, thereby driving testis development within the B6-Y(POS) background. Through 30 years of backcrossing, this congenic region was maintained, as it promoted male sex determination and fertility despite the female-promoting B6-Y(POS) genetic background. Our findings demonstrate that long-range enhancer regions are critical to developmental processes and can be used to identify the complex interplay between genome variants, epigenetics, and developmental gene regulation.

  5. Cucurbita spp. and Cucumis sativus enhance the dissipation of polychlorinated biphenyl congeners by stimulating soil microbial community development.

    Science.gov (United States)

    Qin, Hua; Brookes, Philip C; Xu, Jianming

    2014-01-01

    A number of Cucurbita species have the potential to extract polychlorinated biphenyls (PCBs) from soil, but their impact on the soil microbial communities responsible for PCB degradation remains unclear. A greenhouse experiment was conducted to investigate the effect of three Cucurbita and one Cucumis species on PCB dissipation and soil microbial community structure. Compared to the unplanted control, enhanced losses of PCBs (19.5%-42.7%) were observed in all planted soils. Cucurbita pepo and Cucurbita moschata treatments were more efficient in PCB dissipation, and have similar patterns of soil phospholipid fatty acids (PLFAs) and PCB congener profiles. Cucurbita treatments tend to have higher soil microbial biomass than Cucumis. Gram-negative (G(-)) bacteria were significantly correlated with PCB degradation rates (R(2) = 0.719, p Cucurbita related soil microorganisms could play an important role in remediation of PCB contaminated soils.

  6. 正常和糖尿病来源间充质干细胞生物学特性及创面修复效果差异的比较研究%Comparison of biological characteristics of mesenchymal stem cells from normal and diabetic mice and their treatment effects on wound healing

    Institute of Scientific and Technical Information of China (English)

    高冬蕴; 谷城威; 张振中; 沈涛; 付小兵; 吴旭

    2014-01-01

    目的:探讨正常和糖尿病来源间充质干细胞(MSCs)的生物学特性及对糖尿病慢性创面修复效果的差异。方法:采用高脂(高糖)饲料饲养1个月、腹腔注射40 mg/kg 链脲佐菌素连续3 d的方法制备糖尿病小鼠模型。取正常及糖尿病模型小鼠股骨和胫骨的骨髓,采用Percoll梯度离心法分离 MSCs,体外扩增,倒置相差显微镜下观察细胞形态学,油红“O”和茜素红染色观察其成脂、成骨细胞分化能力,流式细胞仪检测表面抗原表达,酶联免疫检测细胞增殖能力,凋亡试剂盒检测细胞的抗凋亡能力。16只糖尿病模型小鼠随机分为正常 MSCs治疗组和糖尿病MSCs治疗组(n=8),背部制作直径8 mm圆形全层皮肤缺损创面,分别创周皮下注射2×106个正常和糖尿病小鼠来源MSCs,观察创面愈合情况。结果:相同体外培养条件下,糖尿病小鼠来源的MSCs较正常小鼠来源的 MSCs形成细胞集落的能力差且出现生长抑制的时间早,细胞增殖分化能力弱,抗凋亡能力下降,流式细胞术结果显示CD29和CD105阳性表达下降。正常MSCs显示出更好地促进糖尿病慢性创面愈合的效应,尤其是在伤后7~14 d。结论:糖尿病自体的MSCs治疗能力下降,不是治疗糖尿病创面的最佳种子细胞。%Objective:To explore the biological characteristics and effects on wound healing of mesenchymal stem cells (MSCs)from normal and diabetic mouse.Methods:The diabetic model was replicated by feeding with high fat (high sugar)chow for 1 month and receiving intraperitoneal injection of 40 mg/kg streptozocin for 3 days in mice. MSCs were isolated from bone marrow of normal or diabetic mice,and they were purified by Percoll gradient cen-trifugation and cultured invitro. The growth of normal and diabetic MSCs were observed under phase contrast mi-croscope,and their potential of differentiation to adipocytes and osteocytes were observed by oil red O or alizarin red

  7. Different Responses of an Invasive Clonal Plant Wedelia trilobata and its Native Congener to Gibberellin: Implications for Biological Invasion.

    Science.gov (United States)

    Dai, Zhi-Cong; Fu, Wei; Qi, Shan-Shan; Zhai, De-Li; Chen, Si-Chong; Wan, Ling-Yun; Huang, Ping; Du, Dao-Lin

    2016-02-01

    The invasive clonal plant Wedelia trilobata contains higher levels of ent-kaurane diterpenes, which are precursors of gibberellins (GAs), and higher rates of clonal growth than its native congener W. chinensis in invaded habitats. We hypothesized that the higher levels of endogenous GAs facilitate greater ramet growth in W. trilobata compared with W. chinensis. We quantified endogenous levels of GA1+3 in the two species and compared their growth responses to the changes of endogenous and exogenous GA3 by using short-term and long-term hydroponics experiments. After a period of homogeneous cultivation, levels of endogenous GA1+3 were higher in W. trilobata than in W. chinensis. The reduction of endogenous GAs repressed the emergence of adventitious roots and the growth of W. trilobata in the initial cultivation stage, and inhibited its shoot elongation and biomass. Levels of endogenous GA1+3 were positively correlated with the length of shoots and adventitious roots of W. trilobata. Adventitious roots of W. trilobata also emerged earlier and grew faster when treated with exogenous GA3. In contrast, exogenous GA3 treatment inhibited the length of adventitious roots in W. chinensis, and levels of endogenous GA1+3 did not correlate with shoot or adventitious root length. Our study suggests that GAs accelerate the rapid clonal growth of W. trilobata, more than that of its native congener W. chinensis, illustrating the relationship between plant hormones and the clonal growth of invasive plants. These findings are important for understanding the mechanisms associated with the invasiveness of clonal plants and their potential management.

  8. Congener-specific concentrations and carbon stable isotope ratios (delta13C) of two technical toxaphene products (Toxaphene and Melipax).

    Science.gov (United States)

    Vetter, Walter; Gleixner, Gerd; Armbruster, Wolfgang; Ruppe, Steffen; Stern, Gary A; Braekevelt, Eric

    2005-01-01

    In this study we compared the contribution of individual congeners and the ratios of stable carbon isotopes of two technical toxaphene products. The former US-American product Toxaphene was from 1978 and the East-German product Melipax from 1979. Both technical products showed the known complexity in GC/ECD measurements. Contributions of 24 peaks to each of the technical products were determined by gas chromatography in combination high resolution electron capture negative ion mass spectrometry (GC/ECNI-HRMS). The percentages of the compounds studied in the technical mixtures ranged from approximately 0.05% to approximately 2.5% but showed some individual differences. 2,2,5,5,8,9,9,10,10-nonachlorobornane (B9-1025 or P-62) was identified as a major congener in both mixtures. 2-Endo,3-exo,5-endo,6-exo,8,8,10,10-octachlorobornane (B8-1413 or P26) and 2-endo,3-exo,5-endo,6-exo,8,8,9,10,10-nonachlorobornane (B9-1679 or P-50) were found at similar concentration in both technical products. Identical amounts of Melipax or Toxaphene were combusted to CO2 in an element analyzer and their delta13C values were determined relative to the international standard Vienna PeeDee belemnite (VPDB). The mean delta13C values of both products varied by 2.8% (determined at two different locations) which is roughly one order of magnitude more than the precision obtained in repetitive analyses of the individual products. Thus, both investigated products could be unequivocally distinguished by stable isotope ratio mass spectrometry (IRMS). IRMS analyses may thus be a suitable tool for tracing back toxaphene residues in environmental and food samples to the one or both of the products.

  9. (+)Lysergic acid diethylamide, but not its nonhallucinogenic congeners, is a potent serotonin 5HT1C receptor agonist

    Energy Technology Data Exchange (ETDEWEB)

    Burris, K.D.; Breeding, M.; Sanders-Bush, E. (Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (United States))

    1991-09-01

    Activation of central serotonin 5HT2 receptors is believed to be the primary mechanism whereby lysergic acid diethylamide (LSD) and other hallucinogens induce psychoactive effects. This hypothesis is based on extensive radioligand binding and electrophysiological and behavioral studies in laboratory animals. However, the pharmacological profiles of 5HT2 and 5HT1C receptors are similar, making it difficult to distinguish between effects due to activation of one or the other receptor. For this reason, it was of interest to investigate the interaction of LSD with 5HT1C receptors. Agonist-stimulated phosphoinositide hydrolysis in rat choroid plexus was used as a direct measure of 5HT1C receptor activation. (+)LSD potently stimulated phosphoinositide hydrolysis in intact choroid plexus and in cultures of choroid plexus epithelial cells, with EC50 values of 9 and 26 nM, respectively. The effect of (+)LSD in both systems was blocked by 5HT receptor antagonists with an order of activity consistent with interaction at 5HT1C receptors. Neither (+)-2-bromo-LSD nor lisuride, two nonhallucinogenic congeners of LSD, were able to stimulate 5HT1C receptors in cultured cells or intact choroid plexus. In contrast, lisuride, like (+)LSD, is a partial agonist at 5HT2 receptors in cerebral cortex slices and in NIH 3T3 cells transfected with 5HT2 receptor cDNA. The present finding that (+)LSD, but not its nonhallucinogenic congeners, is a 5HT1C receptor agonist suggests a possible role for these receptors in mediating the psychoactive effects of LSD.

  10. Testing for normality

    CERN Document Server

    Thode, Henry C

    2002-01-01

    Describes the selection, design, theory, and application of tests for normality. Covers robust estimation, test power, and univariate and multivariate normality. Contains tests ofr multivariate normality and coordinate-dependent and invariant approaches.

  11. Dopamine-dependent behavior in adult rats after perinatal exposure to purity-controlled polychlorinated biphenyl congeners (PCB52 and PCB180).

    Science.gov (United States)

    Lilienthal, Hellmuth; Heikkinen, Päivi; Andersson, Patrik L; van der Ven, Leo T M; Viluksela, Matti

    2014-01-03

    Since knowledge about toxic effects of non-dioxinlike (NDL) PCBs is fragmentary, regulatory panels have concluded that risk assessment of these congeners is hampered or impossible. As the dopaminergic system is one of the main targets in PCB-related neurotoxic effects after developmental exposure, we selected catalepsy induced by the dopamine receptor blocker haloperidol to characterize effects of the NDL congeners PCB52 and PCB180 in adult offspring from exposed rat dams. Rat dams were treated with PCB congeners by gavage using six dose levels (total doses: PCB52 - 0, 30, 100, 300, 1000 or 3000 mg/kg body wt.; PCB180 - 0, 10, 30, 100, 300, or 1000 mg/kg body wt.) to allow benchmark dose analysis of the results. Testing of adult offspring (starting at 180 days of age) for catalepsy induced by injection with haloperidol revealed slightly prolonged latencies to movement onset in female offspring exposed to PCB52. Exposure to PCB180 resulted in more pronounced effects, with generally reduced latencies in male offspring. These results indicate reduced dopaminergic activity after PCB52 exposure, whereas the outcome for PCB180 may be related to increased extracellular dopamine as reported in the literature.Benchmark dose analyses revealed that both PCB congeners exerted effects mainly at moderate exposure levels. Together, these results underline the importance of effects on the dopaminergic system as indicated by studies in human females after occupational PCB exposure.

  12. Coexposure of dioxin-like polychlorinated biphenyls and polychlorinated dibenzo-p-dioxins and dibenzofurans in free-range hens and implications derived from congener profile analysis.

    Science.gov (United States)

    Lin, Chingju; Hsu, Jing-Fang; Liao, Pao-Chi

    2012-02-29

    The consumption of free-range eggs is becoming more popular worldwide. We analyzed the levels of 12 dioxin-like polychlorinated biphenyls (dl-PCBs) and their congener profiles from 6 free-range and 12 caged egg samples. The mean levels of dl-PCBs in the free-range samples were 5.4 times higher than those in caged eggs. All egg samples exhibited at least two characteristic dl-PCB congener patterns, which reflected distinctive contamination sources. Additionally, for the first time, we demonstrated that the dl-PCB levels in the free-range eggs were highly correlated with elevated levels of 17 polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) (r = 0.986; p < 0.001), indicating a coexposure scenario in free-range hens. Cluster analysis of congener patterns implied that this coexposure scenario could be attributed to distinct dl-PCB and PCDD/F sources. This congener profile information provides insights from a different perspective for further identifying potential dl-PCB and PCDD/F sources in the polluted free-range eggs.

  13. Tissue Distribution of Polychlorinated Biphenyls and Organochlorine Pesticides and Potential Toxicity to Alaskan Northern Fur Seals Assessed Using PCBs Congener Specific Mode of Action Schemes

    Science.gov (United States)

    The concentrations of 145 polychlorinated biphenyl (PCB) congeners were measured using gas chromatography-ion trap mass spectrometry in 8 different tissues (blubber, brain, heart, kidney, liver, lung, muscle, and reproductive tissues) of 10 Alaskan northern fur seals. The mean concentrations of bot...

  14. USING BASE-SPECIFIC SALMONELLA TESTER STRAINS TO CHARACTERIZE THE TYPES OF MUTATION INDUCED BY BENZIDINE AND BENZIDINE CONGENERS AFTER REDUCTIVE METABOLISM

    Science.gov (United States)

    Abstract Benzidine, 4-aminobiphenyl, 3,3'-dichlorobenzidine HCl, 3,3'-dimethylbenzidine, 3,3'- dimethoxybenzidine and benzidine congener-based dye trypan blue were mutagenic in Salmonella typhimurium TAl 00 only with metabolic activation. It was found that a hamster liver 89 ...

  15. Phenomenological and Spectroscopic Analysis on the Effects of Sediment Ageing and Organic Carbon on the Fate of a PCB Congener Spiked to Sediment

    Science.gov (United States)

    This study assesses the full cycle transport and fate of a polychlorinated biphenyl (PCB) congener spiked to sediment to empirically and spectroscopically investigate the effects of sediment ageing and organic carbon on the adsorption, desorption, and reaction of the PCB. Caesar ...

  16. Normal gut microbiota modulates brain development and behavior

    National Research Council Canada - National Science Library

    Rochellys Diaz Heijtz; Shugui Wang; Farhana Anuar; Yu Qian; Britta Björkholm; Annika Samuelsson; Martin L. Hibberd; Hans Forssberg; Sven Pettersson; Arturo Zychlinsky

    2011-01-01

    ...) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor...

  17. Polybrominated diphenyl ether congeners in the young-of-the-year bluefish, Pomatomus saltatrix, from several nursery habitats along the US Atlantic coastline.

    Science.gov (United States)

    Deshpande, Ashok D; Dockum, Bruce W

    2013-12-15

    Spatial trends of polybrominated diphenyl ether (PBDE) congeners were examined by using high resolution gas chromatography-low resolution electron impact mass spectrometry (GC-EIMS) in 414 samples of young-of-the-year (YOY) bluefish (Pomatomus saltatrix) collected from a total of 29 nursery habitats along the US Atlantic coastline from Massachusetts to Florida. Of the 26 target PBDE congeners, BDE-47 (4 Br), BDE-100 (5 Br), BDE-49 (4 Br), BDE-99 (5 Br), and BDE-154 (6 Br) were the five most frequently detected congeners in the order of decreasing importance. The sum of the concentrations of five major PBDE congeners, referred to as ΣPBDEs, varied between estuaries and also among samples from a given estuary. ΣPBDEs were lowest in YOY bluefish from Vineyard Sound, Nantucket Sound, Great Bay, Delaware Bay, Lynnhaven Bay, Cape Lookout, and Crescent Beach, with maximum ΣPBDE concentrations below 10 ng/g wet weight. ΣPBDEs in three bluefish samples from Stamford Harbor were detected at relatively high to unusually high concentrations of 69.1, 205, and 561 ng/g wet weight. ΣPBDE values for other Stamford Harbor bluefish were generally low. Highest PBDE concentrations were detected in the vicinity of industrial and urban locations within the New York-New Jersey metropolitan complex. Among them, bluefish from Newark Bay were generally the most contaminated with an average ΣPBDE value of 56.6 ± 30.8 ng/g wet weight. ΣPBDEs in bluefish from Newark Bay were numerically greater than ΣPBDEs in bluefish from all locations, however these differences were not statistically significant. Modest to good correlations between ΣPBDEs and lipids were observed for YOY bluefish from Buzzards Bay, Upper New Bedford Harbor, Lower New Bedford Harbor, Outer New Bedford Harbor, Providence Harbor, Housatonic River, Norwalk Harbor, Little Neck Bay, Newark Bay, Sandy Hook Bay, Great Bay, Delaware Bay, Patuxent River and Crescent Beach. Poor correlations between ΣPBDE and lipids were

  18. Splenic T helper cell type 1 cytokine profile and extramedullary haematopoiesis in severe combined immunodeficient (scid) mice with inflammatory bowel disease (IBD)

    DEFF Research Database (Denmark)

    Bregenholt, S; Claesson, Mogens Helweg

    1998-01-01

    -transplanted scid mice with IBD. Increased fractions of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-2-positive CD4+ T cells were found in the spleens of diseased mice compared with control mice. Moreover, a small but significant population of CD4+ T cells which stained positive...... for granulocyte-macrophage colony-stimulating factor (GM-CSF) was found in scid mice with IBD but was virtually absent in congenic non-scid control mice. Cloning of granulocyte/ macrophage colony-forming cells (G/M-CFC) revealed that both non-transplanted scid mice and scid mice with IBD had an 8-14-fold increase...

  19. Differential Inequalities, Normality and Quasi-Normality

    CERN Document Server

    Liu, Xiaojun; Pang, Xuecheng

    2011-01-01

    We prove that if D is a domain in C, alpha>1 and c>0, then the family F of functions meromorphic in D such that |f'(z)|/(1+|f(z)|^alpha)>c for every z in D is normalin D. For alpha=1, the same assumptions imply quasi-normality but not necessarily normality.

  20. Triggering the Formation of Direct Collapse Black Holes by Their Congeners

    Science.gov (United States)

    Yue, Bin; Ferrara, Andrea; Pacucci, Fabio; Omukai, Kazuyuki

    2017-04-01

    Direct collapse black holes (DCBHs) are excellent candidates for seeds of supermassive black holes observed at z ≳ 6. The formation of a DCBH requires a strong external radiation field to suppress H2 formation and cooling in a collapsing gas cloud. Such a strong field is not easily achieved by first stars or normal star-forming galaxies. Here we investigate a scenario in which a previously formed DCBH can provide the necessary radiation field for the formation of additional ones. Using a one-zone model and simulated DCBH Spectral Energy Distributions (SEDs) filtered through absorbing gas initially having column density N H, we derive the critical field intensity, {J}{LW}{crit}, to suppress H2 formation and cooling. For the SED model with {N}{{H}}=1.3× {10}25 cm‑2, 8.0 × 1024 cm‑2, and 5.0 × 1024 cm‑2, we obtain {J}{LW}{crit}≈ 22, 35, and 54, all much smaller than the critical field intensity for normal star-forming galaxies {J}{LW}{crit}≳ 1000 X-ray photons from previously formed DCBHs build up a high-z X-ray background (XRB) that may boost the {J}{LW}{crit}. However, we find that in the three SED models, {J}{LW}{crit} only increases to ≈80, 170, and 390, even when {\\dot{ρ }}\\bullet reaches the maximum value allowed by the present-day XRB level (0.22, 0.034, 0.006 M ⊙ yr‑1 Mpc‑3), which is still much smaller than the galactic value. Although considering the XRB from first galaxies may further increase {J}{LW}{crit}, we conclude that our investigation supports a scenario in which DCBHs may be more abundant than predicted by models only including galaxies as external radiation sources.

  1. Long-range atmospheric transport of three toxaphene congeners across Europe. Modeling by chained single-box FATEMOD program.

    Science.gov (United States)

    Paasivirta, Jaakko; Sinkkonen, Seija; Nikiforov, Vladimir; Kryuchkov, Fedor; Kolehmainen, Erkki; Laihia, Katri; Valkonen, Arto; Lahtinen, Manu

    2009-03-01

    Since toxaphene (polychlorocamphene, polychloropinene, or strobane) mixtures were applied for massive insecticide use in the 1960s to replace the use of DDT, some of their congeners have been found at high latitudes far away from the usage areas. Especially polychlorinated bornanes have demonstrated dominating congeners transported by air up to the Arctic areas. Environmental fate modeling has been applied to monitor this phenomenon using parallel zones of atmosphere around the globe as interconnected environments. These zones, shown in many meteorological maps, however, may not be the best way to configure atmospheric transport in air trajectories. The latter could also be covered by connecting a chain of simple model boxes. We aim to study this alternative approach by modeling the trajectory chain using catchment boxes of our FATEMOD model. Polychlorobornanes analyzed in biota of the Barents Sea offered one case to study this modeling alternative, while toxaphene has been and partly still is used massively at southern East Europe and around rivers flowing to the Aral Sea. Pure model substances of three polychlorobornanes (toxaphene congeners P26, P50, and P62) were synthesized, their environmentally important thermal properties measured by differential scanning calorimetry, as evaluated from literature data, and their temperature dependences estimated by the QSPR programs VPLEST, WATSOLU, and TDLKOW. The evaluated property parameters were used to model their atmospheric long-range transport from toxaphene heavy usage areas in Ukraine and Aral/SyrDarja/AmuDarja region areas, through East Europe and Northern Norway (Finnmarken) to the Barents Sea. The time period used for the emission model was June 1997. Usual weather conditions in June were applied in the model, which was constructed by chaining FATEMOD model boxes of the catchment's areas along assumed maximal air flow trajectories. Analysis of the three chlorobornanes in toxaphene mixtures function as a basis

  2. Mast cell-glia axis in neuroinflammation and therapeutic potential of the anandamide congener palmitoylethanolamide.

    Science.gov (United States)

    Skaper, Stephen D; Facci, Laura

    2012-12-05

    Communication between the immune and nervous systems depends a great deal on pro-inflammatory cytokines. Both astroglia and microglia, in particular, constitute an important source of inflammatory mediators and may have fundamental roles in central nervous system (CNS) disorders from neuropathic pain and epilepsy to neurodegenerative diseases. Glial cells respond also to pro-inflammatory signals released from cells of immune origin. In this context, mast cells are of particular relevance. These immune-related cells, while resident in the CNS, are able to cross a compromised blood-spinal cord and blood-brain barrier in cases of CNS pathology. Emerging evidence suggests the possibility of mast cell-glia communication, and opens exciting new perspectives for designing therapies to target neuroinflammation by differentially modulating the activation of non-neuronal cells normally controlling neuronal sensitization-both peripherally and centrally. This review aims to provide an overview of recent progress relating to the pathobiology of neuroinflammation, the role of glia, neuro-immune interactions involving mast cells and the possibility that glia-mast cell interactions contribute to exacerbation of acute symptoms of chronic neurodegenerative disease and accelerated disease progression, as well as promotion of pain transmission pathways. Using this background as a starting point for discussion, we will consider the therapeutic potential of naturally occurring fatty acid ethanolamides, such as palmitoylethanolamide in treating systemic inflammation or blockade of signalling pathways from the periphery to the brain in such settings.

  3. Development of toxic equivalency factors for PCB congeners and the assessment of TCDD and PCB mixtures in rainbow trout

    Science.gov (United States)

    Newsted, John L.; Jones, Paul D.; Giesy, John P.; Crawford, Robert A.; Ankley, Gerald T.; Tillitt, Donald E.; Gooch, Jay W.; Denison, Michael S.

    1995-01-01

    This study was undertaken to evaluate the relationship between mammalian and piscine 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalency factors (TEFs) for PCBs, based on induction of CYP1A enzyme activity, catalytic protein, and mRNA. Rainbow trout administered a single i.p. injection of TCDD had an average (±SD) ED50 of 0.91 ± 0.14 μg TCDD/kg for induction of ethoxyresorufin O-deethylase (EROD) activity. Ortho-substituted PCB congeners 2,3,3′,4,4′-pentachlorobiphenyl (PCB 105), 2,3′,4,4′,5-pentachlorobiphenyl (PCB 118), 2,3,3′4,4′5-hexachlorobiphenyl (PCB !56), and 2,2′3,4,4′,5-hexachlorobiphenyl (PCB 138) did not induce CYP1A activity in rainbow trout. Only three non-ortho-substituted PCBs, i.e., 3,3′4,4′-tetrachlorobiphenyl (PCB 77), 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126), and 3,3′4,4′5,5′-hexachlorobiphenyl (PCB 169) induced CYP1A enzyme activity, protein, and mRNA. The ED50s for induction of EROD activity were calculated as 134, 5.82, and 93.7 μg/kg for PCB 77, PCB 126, and PCB 169, respectively. The TCDD-TEFs based on EROD activity were 0.0006, 0.0014, and 0.0003 for PCB 77, PCB 126, and PCB 169, respectively. Binary mixtures of TCDD and three PCBs were also evaluated. Based on EROD activity and CYP1A protein, mixtures of TCDD and PCB 77 were slightly greater than additive. Mixtures of TCDD-PCB 156 and TCDD-PCB 126 were slightly less than additive. Results from these studies indicate that mammal-derived TEFs will underestimate the potency of planar chlorinated hydrocarbon mixtures to induce the CYP1A catalytic activity in rainbow trout. Also, while interactions among PCB congeners and TCDD were somewhat equivocal, they did not greatly differ from predicted additive responses.

  4. Levels and congener distributions of PCDDs, PCDFs and non-ortho PCBs in Belgian foodstuffs--assessment of dietary intake.

    Science.gov (United States)

    Focant, J F; Eppe, G; Pirard, C; Massart, A C; André, J E; De Pauw, E

    2002-07-01

    Congener-specific analyses of 7 polychlorinated dibenzo-p-dioxins (PCDDs), 10 polychlorinated dibenzofurans (PCDFs) and 4 non-ortho (coplanar) polychlorinated biphenyls (cPCBs) were performed on 197 foodstuffs samples of animal origin from Belgium during years 2000 and 2001. All investigated matrices (except horse) present background levels lower than the Belgian non-commercialization value of 5 pg TEQ/g fat. Pork was the meat containing the lowest concentration of both PCDD/Fs and cPCBs. The mean background concentration of 2,3,7,8-TCDD toxicity equivalent in milk was 1.1 pg/g of fat, with a congener distribution typical of non-contaminated milk. The relative contribution of 2,3,7,8-TCDD, 2,3,7,8-TCDF, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF to the PCDD/Fs TEQ was 85+/-7.9% for all investigated matrices. The cPCBs contribution to the total TEQ was 47+/-19.0% for products of terrestrial species and 69+/-20.0% for aquatic species. Once the contribution of cPCBs was added to the TEQ, few foodstuffs such as horse, sheep, beef, eggs and cheese presented levels above the future European guidelines that currently only include PCDD/Fs but will be re-evaluated later in order to include 'dioxin-like' PCBs. Based on levels measured in the samples, the estimation of the dietary intake was 65.3 pg WHO-TEQ/day for PCDD/Fs only (1.00 pg WHO-TEQ/kg bw/day, for a 65 kg person) and 132.9 pg WHO-TEQ/day if cPCBs were included (2.04 pg WHO-TEQ/kg bw/day, for a 65 kg person). Meat (mainly beef), dairy products, and fish each account for roughly one third of the intake.

  5. MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice.

    Directory of Open Access Journals (Sweden)

    Stéphanie Tomé

    Full Text Available Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD (CAG∼100 transgene, when present in a congenic C57BL/6J (B6 background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with

  6. MSH3 polymorphisms and protein levels affect CAG repeat instability in Huntington's disease mice.

    Science.gov (United States)

    Tomé, Stéphanie; Manley, Kevin; Simard, Jodie P; Clark, Greg W; Slean, Meghan M; Swami, Meera; Shelbourne, Peggy F; Tillier, Elisabeth R M; Monckton, Darren G; Messer, Anne; Pearson, Christopher E

    2013-01-01

    Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)∼100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of

  7. Tick-borne thogoto virus infection in mice is inhibited by the orthomyxovirus resistance gene product Mx1.

    OpenAIRE

    1995-01-01

    We show that tick-transmitted Thogoto virus is sensitive to interferon-induced nuclear Mx1 protein, which is known for its specific antiviral action against orthomyxoviruses. Influenza virus-susceptible BALB/c mice (lacking a functional Mx1 gene) developed severe disease symptoms and died within days after intracerebral or intraperitoneal infection with a lethal challenge dose of Thogoto virus. In contrast, Mx1-positive congenic, influenza virus-resistant BALB.A2G-Mx1 mice remained healthy an...

  8. Variation in the strength of reproductive interference from an alien congener to a native species in Taraxacum.

    Science.gov (United States)

    Nishida, Sachiko; Hashimoto, Keisuke; Kanaoka, Masahiro M; Takakura, Ko-Ichi; Nishida, Takayoshi

    2017-01-01

    Reproductive interference (RI) may be a contributing factor to the displacement of native species by an alien congener, and RI strength has been shown theoretically to affect distributional relationships between species. Thus, variations in RI strength from alien to native species result in different consequences of invasions and efforts to conserve native species, but the variations have seldom been examined empirically. We therefore investigated RI strength variations from the alien species Taraxacum officinale and its hybrids to eight populations of native dandelions, four T. japonicum populations and two populations each of two subspecies of T. platycarpum. We examined the association between alien relative abundance and native seed set in field surveys, and we also performed hand-pollination experiments to investigate directly the sensitivity of native flowers to alien pollen. We found that the effect of alien relative abundance on native seed set of even the same native species could differ greatly in different regions, and that the sensitivity of native flowers to alien pollen was also dependent on region. Our results, together with those of previous studies, show that RI from the alien to the native species is strong in regions where the alien species outnumbers the native species and marginal where it does not; this result suggests that alien RI can critically affect distributional relationships between native and alien species. Our study highlights the importance of performing additional empirical investigations of RI strength variation and of giving due attention to alien RI in efforts to conserve regional native biodiversity.

  9. The potential for genetic assimilation of a native dandelion species, Taraxacum ceratophorum (Asteraceae), by the exotic congener T. officinale.

    Science.gov (United States)

    Brock, Marcus T

    2004-05-01

    Exotic plant species can threaten closely related native congeners through asymmetric hybridization and subsequent backcrossing, the process known as genetic assimilation. I explore the initial stages of this process in Taraxacum ceratophorum (Asteraceae), the native alpine dandelion, and the invasive apomict T. officinale. In central Colorado, seven T. ceratophorum populations all occur in sympatry with T. officinale. In one large population on Pennsylvania Mountain, surveys further revealed that flowering phenologies and visiting insect taxa overlap almost completely for both Taraxacum species. Together these results indicated that heterospecific pollen transfer is likely. Crossing experiments showed that T. ceratophorum is an obligate outcrosser, and interspecific hand pollinations resulted in 37.3% seed set. However, molecular analysis of the F1 offspring indicated that only 33.2% of germinating seeds were hybrids; the remainder were selfed offspring produced from a breakdown in self-incompatibility (the mentor effect). Although the mentor effect helps reduce the production of hybrids, the asymmetrical direction of hybridization creates the potential for genetic assimilation of T. ceratophorum by T. officinale.

  10. Passive air monitoring of PCBs and PCNs across East Asia: a comprehensive congener evaluation for source characterization.

    Science.gov (United States)

    Hogarh, Jonathan Nartey; Seike, Nobuyasu; Kobara, Yuso; Habib, Ahsan; Nam, Jae-Jak; Lee, Jong-Sik; Li, Qilu; Liu, Xiang; Li, Jun; Zhang, Gan; Masunaga, Shigeki

    2012-02-01

    A comprehensive congener specific evaluation of polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) in the atmosphere was conducted across East Asia in spring 2008, applying polyurethane foam (PUF) disk passive air sampler (PAS) as monitoring device. Mean concentrations derived for Japan, China and Korea were 184 ± 24, 1100 ± 118, and 156 ± 20 pg m(-3) for ∑(202) PCBs, and 9.5 ± 1.5, 61 ± 6, and 16 ± 2.4 pg m(-3) for ∑(63) PCNs, respectively. Relative to reported data from 2004, the present results suggest that air PCBs concentrations have not changed much in Japan and Korea, while it has increased by one order of magnitude in China. From principal component analysis, combustion emerged highly culpable in contemporary emissions of both PCBs and PCNs across the East Asian sub-region. Another factor derived as important to air PCBs was re-emissions/volatilization. Signals from PCBs formulations were also picked, but their general importance was virtually consigned to the re-emissions/volatilization tendencies. On the contrary, counterpart PCNs formulations did not appear to contribute much to air PCNs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. EXPERIMENTAL-INFECTION IN MICE WITH BACILLUS-LICHENIFORMIS

    DEFF Research Database (Denmark)

    Agerholm, J.S.; Jensen, H.E.; Jensen, N.E.

    1995-01-01

    The pathogenicity of Bacillus licheniformis was assessed in normal and immunodepressed BALB/c mice. The animals were challenged intravenously with 4 x 10(7) colony forming units of B, licheniformis (ATCC 14580) and both normal and immunodepressed mice were susceptible. However, the infection...... was more severe in the immunosuppressed animals. In normal mice, lesions were restricted to the liver and kidneys, while lesions also occurred in other organs of immunodepressed mice. By crossed immunoelectrophoresis it was shown that antigens of B. licheniformis are potent immunogens, and the bacteria...

  12. Multivariate toxicity profiles and QSAR modeling of non-dioxin-like PCBs--an investigation of in vitro screening data from ultra-pure congeners.

    Science.gov (United States)

    Stenberg, Mia; Hamers, Timo; Machala, Miroslav; Fonnum, Frode; Stenius, Ulla; Lauy, Al-Anati; van Duursen, Majorie B M; Westerink, Remco H S; Fernandes, Elsa C Antunes; Andersson, Patrik L

    2011-11-01

    The non-dioxin-like PCBs (NDL-PCBs) found in food and human samples have a complex spectrum of adverse effects, but lack a detailed risk assessment. The toxicity profiles of 21 carefully selected PCBs (19 NDL-PCBs) were identified by in vitro screening in 17 different assays on specific endpoints related to neurotoxicity, endocrine disruption and tumor promotion. To ensure that the test results were not affected by polychlorinated dioxins, dibenzofurans or DL-PCB contaminants, the NDL-PCB congeners were thoroughly purified before testing. Principal component analysis (PCA) was used to derive general toxicity profiles from the in vitro screening data. The toxicity profiles indicated different structure-activity relationships (SAR) and distinct mechanisms of action. The analysis also indicated that the NDL-PCBs could be divided into two groups. The first group included generally smaller, ortho-substituted congeners, comprising PCB 28, 47, 51, 52, 53, 95, 100, 101, 104 and 136, with PCB 95, 101 and 136 as generally being most active. The second group comprising PCB 19, 74, 118, 122, 128, 138, 153, 170, 180 and 190 had lower biological activity in many of the assays, except for three endocrine-related assays. The most abundant congeners, PCB 138, 153, 170, 180 and 190, cluster in the second group, and thereby show similar SAR. Two quantitative structure-activity relationship (QSAR) models could be developed that added information to the SAR and could aid in risk assessments of NDL-PCBs. The QSAR models predicted a number of congeners as active and among these e.g., PCB 18, 25, 45 and 49 have been found in food or human samples.

  13. Thermolysis of Iso-Migrastatin and Its Congeners via [3,3]-Sigmatropic Rearrangement: A New Route to the Synthesis of Migrastatin and Its Analogues

    Science.gov (United States)

    Ju, Jianhua; Lim, Si-Kyu; Jiang, Hui; Seo, Jeong-Woo; Her, Yeng; Shen, Ben

    2008-01-01

    Thermolysis of iso-migrastatin (1) under neat heating conditions afforded migrastatin (1a). The reaction is proposed to proceed via a concerted [3,3]-sigmatropic rearrangement by which ring expansion is achieved regio- and enantio-specifically. The general applicability of this reaction was demonstrated with six additional iso-migrastatin congeners (3 – 8), providing a new route to the synthesis of migrastatin analogs (3a – 8a). PMID:17134292

  14. Hepatic in vitro toxicity assessment of PBDE congeners BDE47, BDE153 and BDE154 in Atlantic salmon (Salmo salar L.)

    Energy Technology Data Exchange (ETDEWEB)

    Softeland, Liv, E-mail: lso@nifes.no [National Institute of Nutrition and Seafood Research, PO Box 2029 Nordnes, N-5817 Bergen (Norway); Petersen, Kjell [Computational Biology Unit, Bergen Centre for Computational Science, Uni Research AS, Thormohlensgt 55, N5008 Bergen (Norway); Stavrum, Anne-Kristin [Dept of Clinical Medicine, University of Bergen (Norway); Wu, Terence [Yale University W.M. Keck Biotechnology Resource, 300 George St., Room G001, New Haven, CT 06511 (United States); Olsvik, Pal A. [National Institute of Nutrition and Seafood Research, PO Box 2029 Nordnes, N-5817 Bergen (Norway)

    2011-10-15

    The brominated flame retardant congeners BDE47, BDE153 and BDE154 are among the congeners accumulating to the highest degree in fish. In order to gain knowledge about the toxicological effects of PBDEs in fish, microarray-based transcriptomic and 2D-DIGE/MALDI-TOF/TOF proteomic approaches were used to screen for effects in primary Atlantic salmon hepatocytes exposed to these congeners alone or in combination (PBDE-MIX). A small set of stress related transcripts and proteins were differentially expressed in the PBDE exposed hepatocytes. The PBDE-MIX, and BDE153 to a lesser degree, seems to have induced metabolic disturbances by affecting several pathways related to glucose homeostasis. Further, effects on cell cycle control and proliferation signal pathways in PBDE-MIX-exposed hepatocytes clearly suggest that the PBDE exposure affected cell proliferation processes. CYP1A was 7.41- and 7.37-fold up-regulated in hepatocytes exposed to BDE47 and PBDE-MIX, respectively, and was the only biotransformation pathway affected by the PBDE exposure. The factorial design and PLS regression analyses of the effect of the PBDE-MIX indicated that BDE47 contributed the most to the observed CYP1A response, suggesting that this congener should be incorporated in the toxic equivalent (TEQ) concept in future risk assessment of dioxin-like chemicals. Additionally, a significant up-regulation of the ER-responsive genes VTG and ZP3 was observed in cells exposed to BDE47 and PBDE-MIX. Further analyses suggested that BDE47 and BDE154 have an estrogenic effect in male fish. The data also suggested an antagonistic interaction between BDE153 and BDE154. In conclusion, this study shows that PBDEs can affect several biological systems in Atlantic salmon cells, and demonstrates the need for more studies on the simultaneous exposure to chemical mixtures to identify combined effects of chemicals.

  15. Correcting the gas and particle partitioning of PCDD/F congeners in the flue gas of an iron ore sinter plant.

    Science.gov (United States)

    Kuo, Yu-Chieh; Chen, Yu-Cheng; Yang, Jeng-How; Tsai, Perng-Jy; Wang, Lin-Chi; Chang-Chien, Guo-Ping

    2012-03-30

    This study was aimed at developing an approach for correcting the gas and particle partitioning of PCDD/F congeners for samples collected from the flue gas of an iron ore sinter plant. An iron ore sinter plant equipped with an electrostatic precipitator (EP) and a selective catalytic reduction (SCR) was selected. Flue gas samples were collected at EP inlet, EP outlet and SCR outlet. Both particle- and gas-phase PCDD/Fs were analyzed for each collected sample. PCDD/F contents in EP ashes (EP(ash)) were also analyzed and used to correct the gas and particle partitioning of PCDD/F congeners of the collected flue gas samples. Results show that PCDD/Fs in the flue gas were dominated by the gas-phase. Before correction, the removal efficiencies for the gas- and particle-phase PCDD/Fs for EP were -58.1% and 64.3%, respectively, and SCR were 39.4% and 83.9%, respectively. The above results were conflict with the expected results for both EP and SCR indicating the need for correcting the gas and particle partitioning of PCDD/F congeners for all collected flue gas samples. After correction, the removal efficiencies become more reasonable for EP (=4.22% and 97.7%, respectively), and SCR (=54.7% and 62.0%, respectively). The above results confirm the effectiveness of the approach developed by this study. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Levels and congener profiles of PCBs and PCDD/Fs in blue shark (Prionace glauca) liver from the South-Eastern Mediterranean Sea (Italy).

    Science.gov (United States)

    Storelli, Maria Maddalena; Barone, Grazia; Storelli, Arianna; Marcotrigiano, Giuseppe Onofrio

    2011-01-01

    Liver of blue shark (Prionace glauca) specimens from the South-Eastern Mediterranean Sea were analyzed for the presence of polychlorinated biphenyls (PCBs), including coplanar congeners, polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). PCBs were the dominant chemicals, followed by PCDFs and PCDDs. The pattern of PCB congener concentrations in the hepatic tissue was dominated by higher chlorinated compounds. The specific profile of toxic PCDD/F congeners was characterized mainly by 2,3,7,8-TCDF and 2,3,7,8-TCDD, followed by 1,2,3,6,7,8-HxCDD and 2,3,4,6,7,8-HxCDF. The total 2,3,7,8-TCDD toxic equivalent (TEQs) was 149 pg g⁻¹ lipid wt. The profile of TEQ shows that PCDDs present the greatest risk to this species contributing to total toxicity with a percentage approximately of 60%, while the contribution of PCDFs and DL-PCBs is almost the same being 22.4% and 21.6%, respectively. Further investigations are urgently needed to characterize the PCDD/Fs contamination levels not only in elasmobranch fish but in all Mediterranean marine biota. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Prenatal exposure to a polychlorinated biphenyl (PCB congener influences fixation duration on biological motion at 4-months-old: a preliminary study.

    Directory of Open Access Journals (Sweden)

    Hirokazu Doi

    Full Text Available Adverse effects of prenatal exposure to polychlorinated biphenyl (PCB congeners on postnatal brain development have been reported in a number of previous studies. However, few studies have examined the effects of prenatal PCB exposure on early social development. The present study sought to increase understanding of the neurotoxicity of PCBs by examining the relationship between PCB congener concentrations in umbilical cord blood and fixation patterns when observing upright and inverted biological motion (BM at four-months after birth. The development of the ability to recognize BM stimuli is considered a hallmark of socio-cognitive development. The results revealed a link between dioxin-like PCB #118 concentration and fixation pattern. Specifically, four-month-olds with a low-level of prenatal exposure to PCB #118 exhibited a preference for the upright BM over inverted BM, whereas those with a relatively high-level of exposure did not. This finding supports the proposal that prenatal PCB exposure impairs the development of social functioning, and indicates the importance of congener-specific analysis in the risk analysis of the adverse effects of PCB exposure on the brain development.

  18. Concentrations and congener profiles of polybrominated diphenyl ethers (PBDEs) in blood plasma from Hong Kong: implications for sources and exposure route.

    Science.gov (United States)

    Wang, Hong-Sheng; Jiang, Guan-Min; Chen, Zhuo-Jia; Du, Jun; Man, Yu-Bon; Giesy, John P; Wong, Chris K C; Wong, Ming-Hung

    2013-10-15

    There was limited information about bioaccumulation of polybrominated diphenyl ethers (PBDEs) in humans of the general population of Hong Kong. Therefore, the present study was conducted to determine concentrations and congener profiles of PBDEs in blood plasma from Hong Kong, evaluate their sources and correlations with other organobrominated compounds, and investigate exposure routes from fish and dust. Concentrations of ∑PBDE22 ranged from 0.56 to 92 ng g(-1), lipid weight (lw), with a median of 5.4 ng g(-1). BDE-47 was the dominant congener, accounting for 26% of ∑PBDE22. Concentrations of PBDE congeners in market fish were significantly (r(2)=0.89, pPBDEs. Furthermore, our data revealed a spatial distribution and terrestrial source of BDE-28 for local people. Results of the present study, which was the first systematic study to investigate concentrations of PBDEs in blood of Hong Kong people, provides useful information to which future measurements can be compared.

  19. Long-range atmospheric transport of PAHs, PCBs and PBDEs to the central and eastern Mediterranean and changes of PCB and PBDE congener patterns in summer 2010

    Science.gov (United States)

    Mulder, Marie D.; Heil, Angelika; Kukučka, Petr; Kuta, Jan; Přibylová, Petra; Prokeš, Roman; Lammel, Gerhard

    2015-06-01

    The central and eastern Mediterranean is a receptor area for persistent organic pollutants (POPs) emitted in western, central and eastern Europe, particularly during summer. Atmospheric concentrations of PCBs, DDXs, PBDEs, penta- and hexachlorobenzene were measured during a ship-borne survey in the summer of 2010. The concentration of PCBs (sum of 7 congeners) was 3.61 (2.08-7.72) pg m-3, of which 6.7% was associated with the particulate phase. The mean concentration of DDT isomers and their metabolites, DDE and DDD, was 2.60 (0.46-7.60) pg m-3 (particulate mass fraction θ = 0.097), of penta- and hexachlorobenzene 0.22 (PBDEs (sum of 8 congeners) 7.31 (2.80-19.89) pg m-3. The air masses studied had been transported mostly across central Europe, some crossing western Europe. The observed changes of PCB congener patterns along transport routes are in agreement with the perception that the reaction with the OH radical is dominating PCB atmospheric lifetime, and indicate an overestimation of the second order gas-phase reaction rate coefficient of PCB153 with OH by structure-activity relationship.

  20. Tissue distribution of HCH and DDT congeners and human health risk associated with consumption of fish collected from Kabul River, Pakistan.

    Science.gov (United States)

    Aamir, Muhammad; Khan, Sardar; Nawab, Javed; Qamar, Zahir; Khan, Anwarzeb

    2016-03-01

    Distribution of hexachlorocyclohexane (HCH) and dichlorodiphenyltrichloroethane (DDT) congeners in tissues of four different fish species and their associated potential health risks to local consumers are presented in this paper. The average ∑(HCHs+DDTs) concentration in Glyptothorax punjabensis (214ngg(-1) wet weight (ww)) (carnivores) was found higher than Tor putitora (155ngg(-1) ww) (herbivores). The distribution of ∑(HCHs+DDTs) in all fish tissues was found in order of liver>muscle>stomach>gills. The profile of congeners (β-HCH/∑HCH from 0.29-0.47) indicated that all selected fish species were contaminated with HCH because of its recent usage in the study area. Furthermore, DDT profile ((DDE+DDD)/∑DDT from 0.61-0.78) showed that fish contamination with DDT originated from past usage and long-time degradation mechanism. The average estimated daily dietary intake of ∑HCHs (15.0ngkg(-1) day(-1)) was higher than ∑DDTs (12.5ngkg(-1) day(-1)) by the local consumers via fish consumption. On the basis of both 50th and 95th percentile exposure levels, the carcinogenic hazard ratios for DDT and its congeners were exceeded one (safe limit) for all fish species, indicating a great potential cancer risk for local consumers with life time consumption of contaminated fish collected from Kabul River.

  1. Influence of turkey herpesvirus vaccination on the B-haplotype effect on Marek's disease resistance in 15.B-congenic chickens.

    Science.gov (United States)

    Bacon, L D; Witter, R L

    1992-01-01

    Eight recently developed 15.B congenic lines of chickens were tested for Marek's disease (MD) resistance by intra-abdominal injection of cell-associated preparations of MD virus of a virulent strain (JM), a very virulent strain (Md5), or Md5 after vaccination with turkey herpesvirus (HVT) strain FC126. Chickens of the 15.N congenic line (B15B21 or B21B21) were very resistant to JM-induced MD, in contrast to chickens homozygous for the B-haplotypes 2, 5, 12, 13, 15, or 19. After Md5 infection, more than 88% of the chickens in all of the congenic lines developed MD. However, when chickens were vaccinated with HVT before being inoculated with Md5, the B5 and B12 homozygotes were more resistant to MD than were the B2, B13, or B19 homozygotes, and B15 and B21 homozygotes had intermediate resistance. B5B5 and B2B5 F2 chicks inoculated with HVT and Md5 had a lower prevalence of MD than B2B2 sibs. These results demonstrate that a protocol involving HVT vaccination of chicks followed by infection with very virulent MD virus will allow the detection of B-haplotypes determining MD resistance, some of which are not detectable in unvaccinated chicks challenged with virulent MD.

  2. Single Targeted Exon Mutation Creates a True Congenic Mouse for Competitive Hematopoietic Stem Cell Transplantation: The C57BL/6-CD45.1STEM Mouse

    Directory of Open Access Journals (Sweden)

    Francois E. Mercier

    2016-06-01

    Full Text Available Defining the molecular regulators of hematopoietic stem and progenitor cells (HSPCs requires in vivo functional analyses. Competitive bone marrow transplants (BMTs compare control and test HSPCs to demonstrate the functional role of a genetic change or chemical perturbation. Competitive BMT is enabled by antibodies that specifically recognize hematopoietic cells from congenic mouse strains due to variants of the cell surface protein CD45, designated CD45.1 and CD45.2. The current congenic competitor strain, B6.SJL-Ptprca Pepcb/BoyJ (CD45.1, has a substantial inherent disadvantage in competition against the C57BL/6 (CD45.2 strain, confounding experimental interpretation. Despite backcrossing, the congenic interval over which the B6.SJL-Ptprca Pepcb/BoyJ strain differs is almost 40 Mb encoding ∼300 genes. Here, we demonstrate that a single amino acid change determines the CD45.1 epitope. Further, we report on the single targeted exon mutant (STEM mouse strain, CD45.1STEM, which is functionally equivalent to CD45.2 cells in competitive BMT. This strain will permit the precise definition of functional roles for candidate genes using in vivo HSPC assays.

  3. Analysis of biosurfactants from industrially-viable Pseudomonas strain isolated from crude oil suggests how rhamnolipids congeners affect on emulsification property and antimicrobial activity

    Directory of Open Access Journals (Sweden)

    Palashpriya eDas

    2014-12-01

    Full Text Available Rhamnolipid biosurfactants produced mainly by Pseudomonas sp. had been reported to possess a wide range of potential industrial application. These biosurfactants are produced as monorhamnolipid (MRL and di-rhamnolipid (DRL congeners. The present study deals with rhamnolipid biosurfactants produced by three bacterial isolates from crude oil. Biosurfactants produced by one of the strains (named as IMP67 was found to be very efficacious based on its critical micelle concentration (CMC value and hydrocarbon emulsification property. Strikingly, antimicrobial and anti-biofilm potential of this biosurfactant were higher than biosurfactants produced by other two strains. Thin layer chromatography (TLC analysis and rhamnose quantification showed that the rhamnolipids of IMP67 had more MRL congeners than biosurfactants of the other two strains. Emulsification and antimicrobial actions were affected by manual change of MRL and DRL congener proportions. Increase of MRL proportion enhanced emulsification index and antimicrobial property to Gram negative bacteria. This result indicated that the ratio of MRL and DRL affect the emulsification potentials of rhamnolipids, and suggested that high emulsification potentials might enhance rhamnolipids to penetrate the cell wall of Gram negative bacteria. In consistent, rhamnolipids of IMP67 reduced the MIC of some antibiotics against bacteria, suggesting the potential of biosurfactant as antibiotics synergist.

  4. Analysis of biosurfactants from industrially viable Pseudomonas strain isolated from crude oil suggests how rhamnolipids congeners affect emulsification property and antimicrobial activity.

    Science.gov (United States)

    Das, Palashpriya; Yang, Xin-Ping; Ma, Luyan Z

    2014-01-01

    Rhamnolipid biosurfactants produced mainly by Pseudomonas sp. had been reported to possess a wide range of potential industrial application. These biosurfactants are produced as monorhamnolipid (MRL) and di-rhamnolipid (DRL) congeners. The present study deals with rhamnolipid biosurfactants produced by three bacterial isolates from crude oil. Biosurfactants produced by one of the strains (named as IMP67) was found to be very efficacious based on its critical micelle concentration value and hydrocarbon emulsification property. Strikingly, antimicrobial, and anti-biofilm potential of this biosurfactant were higher than biosurfactants produced by other two strains. Thin layer chromatography analysis and rhamnose quantification showed that the rhamnolipids of IMP67 had more MRL congeners than biosurfactants of the other two strains. Emulsification and antimicrobial actions were affected by manual change of MRL and DRL congener proportions. Increase of MRL proportion enhanced emulsification index and antimicrobial property to Gram negative bacteria. This result indicated that the ratio of MRL and DRL affected the emulsification potentials of rhamnolipids, and suggested that high emulsification potentials might enhance rhamnolipids to penetrate the cell wall of Gram negative bacteria. In line with this finding, rhamnolipids of IMP67 also reduced the MIC of some antibiotics against bacteria, suggesting their synergistic role with the antibiotics.

  5. Craniofacial Statistical Deformation Models of Wild-type mice and Crouzon mice

    DEFF Research Database (Denmark)

    Ólafsdóttir, Hildur; Darvann, Tron Andre; Ersbøll, Bjarne Kjær

    2007-01-01

    of Micro CT scannings of the heads of wild-type (normal) mice and Crouzon mice were investigated. Statistical deformation models were built to assess the anatomical differences between the groups, as well as the within-group anatomical variation. Following the approach by Rueckert et al. we built an atlas...

  6. Blood pressure, heart rate and tubuloglomerular feedback in A1AR-deficient mice with different genetic backgrounds.

    Science.gov (United States)

    Kim, S M; Mizel, D; Qin, Y; Huang, Y; Schnermann, J

    2015-01-01

    Differences in genetic background between control mice and mice with targeted gene mutations have been recognized as a potential cause for phenotypic differences. In this study, we have used A1AR-deficient mice in a C57Bl/6 and SWR/J congenic background to assess the influence of background on the effect of A1AR-deficiency on cardiovascular and renal functional parameters. In A1AR+/+ and A1AR-/- mice in C57Bl/6 and SWR/J congenic backgrounds, we assessed blood pressure and heart rate using radio-telemetry, plasma renin concentrations and tubuloglomerular feedback. We did not detect significant differences in arterial blood pressure (MAP) and heart rates (HR) between A1AR+/+ and A1AR-/- mice in either C57Bl/6, SWR/J or mixed backgrounds. MAP and HR were significantly higher in SWR/J than in C57Bl/6 mice. A high NaCl intake increased MAP in A1AR-/- mice on C57Bl/6 background while there was less or no salt sensitivity in the SWR/J background. No significant differences in plasma renin concentration were detected between A1AR-/- and A1AR+/+ mice in any of the strains. Tubuloglomerular feedback was found to be absent in A1AR-/- mice with SWR/J genetic background. While this study confirmed important differences between inbred mouse strains, we did not identify phenotypic modifications of A1AR-related effects on blood pressure, heart rate and plasma renin by differences in genetic background. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  7. Developmental expression of insulin-like growth factor II receptor (IGF-IIR) in congenic mouse embryonic lungs: correlation between IGF-IIR mRNA and protein levels and heterochronic lung development.

    Science.gov (United States)

    Melnick, M; Chen, H; Rich, K A; Jaskoll, T

    1996-06-01

    Embryonic lung maturation in the H-2 congenic pair, B10.A and B10, proceeds at different rates. The dependence of this heterochronic development on maternal haplotype suggests the involvement of a parentally imprinted gene. Since B10.A (H-2a) and B10 (H-2b) mice are genetically identical except for a 3-18 cM region of chromosome 17 that includes the H-2 complex, we sought a promising candidate gene(s) involved in regulating the rate of lung development from genes encoded in this region. The best candidate is the gene encoding the type II insulin-like growth factor receptor (IGF-IIR), whose ligand is the growth factor IGF-II. Only the maternal copy of this gene is expressed in postimplantation embryos. This receptor does not appear to transduce mitogenic signals; instead, IGF-IIR appears to regulate the levels of its ligand available to the growth-promoting type I IGF receptor (IGF-IR). Using in situ hybridization and indirect immunofluorescence, we demonstrate that IGF-IIR mRNA and protein are localized throughout the pulmonary mesenchyme, as well as in branching epithelia of the pseudoglandular and canalicular stages. We also examined the levels of IGF-IIR mRNA and protein expression by RNase protection assay and ligand blotting during the embryonic period of lung development in B10.A and B10 mice, and found that there is a highly significant positive correlation of IGF-IIR levels with progressive development in both strains. Further, slower-developing B10.A lungs contain significantly higher levels of IGF-IIR mRNA and protein than the more rapidly developing B10 lungs. These results suggest that haplotype-dependent elevation of IGF-IIR levels reduces the available concentration of IGF-II, resulting in a decreased rate of morphogenesis in B10.A mice. Heterochronic lung maturation, then, appears consequent to variable extracellular levels of this important growth factor. These results may be of clinical importance to predicting susceptibility to Respiratory

  8. Contamination levels and congener distribution of PCDDs, PCDFs and dioxin-like PCBs in buffalo's milk from Caserta province (Italy).

    Science.gov (United States)

    Esposito, Mauro; Serpe, Francesco Paolo; Neugebauer, Frank; Cavallo, Stefania; Gallo, Pasquale; Colarusso, Germana; Baldi, Loredana; Iovane, Giuseppe; Serpe, Luigi

    2010-04-01

    An extraordinary plan of official control was carried out in 2008 in Campania (Italy) with the aim to monitor polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) levels in buffalo milk and to detect the contaminated farms, most of which are located in Caserta province. For these companies has been ordered seizure and execution of additional analyses has been requested in farms falling in the nearness, within a distance of 3km, for a total of 304 farms examined. Moreover, all non-compliant farms were subjected to a periodic sampling in order to monitor trends in the levels of contamination. In this paper the distribution and the concentrations of 17 PCDD/Fs and 12 dioxin-like PCBs in 460 samples of buffalo milk collected in the province of Caserta (Italy) are presented. The range of WHO-TEQ values for the PCDD/Fs in milk was 0.17pgTEQg(-1)fat and 87.0pgTEQg(-1)fat with a mean value 3.63pgTEQg(-1)fat and medium value 2.25pgTEQg(-1)fat. The concentrations of dioxin-like PCBs in the analysed samples ranged from 0.21pgTEQg(-1)fat to 15.9pgTEQg(-1)fat and the WHO-TEQ values of sum of PCDDs, PCDFs and dl-PCBs ranged from 0.45pgTEQg(-1)fat to 103.0pgTEQg(-1)fat. The geo-referencing analysis allowed to individuate a restricted area of the region object of the present study where is located the majority of the non-compliant farms. The study of the congeners distribution has finally suggested that the likely cause of contamination is to be attributed to the illegal burning of waste. 2010 Elsevier Ltd. All rights reserved.

  9. Cytokine response to the RSV antigen delivered by dendritic cell-directed vaccination in congenic chicken lines.

    Science.gov (United States)

    Mucksová, Jitka; Plachý, Jiří; Staněk, Ondřej; Hejnar, Jiří; Kalina, Jiří; Benešová, Barbora; Trefil, Pavel

    2017-04-05

    Systems of antigen delivery into antigen-presenting cells represent an important novel strategy in chicken vaccine development. In this study, we verified the ability of Rous sarcoma virus (RSV) antigens fused with streptavidin to be targeted by specific biotinylated monoclonal antibody (anti-CD205) into dendritic cells and induce virus-specific protective immunity. The method was tested in four congenic lines of chickens that are either resistant or susceptible to the progressive growth of RSV-induced tumors. Our analyses confirmed that the biot-anti-CD205-SA-FITC complex was internalized by chicken splenocytes. In the cytokine expression profile, several significant differences were evident between RSV-challenged progressor and regressor chicken lines. A significant up-regulation of IL-2, IL-12, IL-15, and IL-18 expression was detected in immunized chickens of both regressor and progressor groups. Of these cytokines, IL-2 and IL-12 were most up-regulated 14 days post-challenge (dpc), while IL-15 and IL-18 were most up-regulated at 28 dpc. On the contrary, IL-10 expression was significantly down-regulated in all immunized groups of progressor chickens at 14 dpc. We detected significant up-regulation of IL-17 in the group of immunized progressors. LITAF down-regulation with iNOS up-regulation was especially observed in the progressor group of immunized chickens that developed large tumors. Based on the increased expression of cytokines specific for activated dendritic cells, we conclude that our system is able to induce partial stimulation of specific cell types involved in cell-mediated immunity.

  10. Occurrence of an invasive coral in the southwest Atlantic and comparison with a congener suggest potential niche expansion.

    Science.gov (United States)

    Carlos-Júnior, Lélis A; Neves, Danilo M; Barbosa, Newton P U; Moulton, Timothy P; Creed, Joel C

    2015-06-01

    Tubastraea tagusensis, a coral native to the Galapagos Archipelago, has successfully established and invaded the Brazilian coast where it modifies native tropical rocky shore and coral reef communities. In order to understand the processes underlying the establishment of T. tagusensis, we tested whether Maxent, a tool for species distribution modeling, based on the native range of T. tagusensis correctly forecasted the invasion range of this species in Brazil. The Maxent algorithm was unable to predict the Brazilian coast as a suitable environment for the establishment of T. tagusensis. A comparison between these models and a principal component analysis (PCA) allowed us to examine the environmental dissimilarity between the two occupied regions (native and invaded) and to assess the species' occupied niche breadth. According to the PCA results, lower levels of chlorophyll-a and nitrate on the Atlantic coast segregate the Brazilian and Galapagos environments, implying that T. tagusensis may have expanded its realized niche during the invasion process. We tested the possible realized niche expansion in T. tagusensis by assuming that Tubastraea spp. have similar fundamental niches, which was supported by exploring the environmental space of T. coccinea, a tropical-cosmopolitan congener of T. tagusensis. We believe that the usage of Maxent should be treated with caution, especially when applied to biological invasion (or climate change) scenarios where the target species has a highly localized native (original) distribution, which may represent only a small portion of its fundamental niche, and therefore a violation of a SDM assumption.

  11. Dioxin congener patterns in commercial catfish from the United States and the indication of mineral clays as the potential source.

    Science.gov (United States)

    Huwe, J K; Archer, J C

    2013-01-01

    Since 1991 the US Department of Agriculture (USDA) has conducted annual surveys of pesticide residues in foods under the Agricultural Marketing Service's Pesticide Data Program (PDP). To assess chemical residues in domestically marketed catfish products, 1479 catfish samples were collected during the 2008-2010 PDPs. A subset of 202 samples was analysed for 17 toxic polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs). The average pattern of the individual PCDD/F congener concentrations in the catfish was rather unique in that it had almost no measurable amounts of polychlorinated dibenzofurans (PCDFs), but all PCDDs were present. This pattern was more dominant in the domestically produced catfish products than in the imported products (China/Taiwan). Comparison of the pattern to known sources of PCDD/Fs showed strong similarities to the pattern of PCDD/Fs found in kaolin clays which have often been used as anti-caking agents in animal feeds. To investigate whether catfish feeds may be the source of the PCDD/Fs found in the catfish, archived catfish feed data from a US Food and Drug Administration (USFDA) database were examined. In 61 out of 112 feed samples, the PCDD concentrations were 50 times higher than the PCDF concentrations and resembled the pattern found in the catfish products and in clays mined in the south-eastern United States. Although the source of PCDD/Fs in domestically marketed catfish products cannot be definitively established, mined clay products used in feeds should be considered a likely source and, given the wide concentration range of PCDD/Fs that has been found in clays, a critical control point for PCDD/Fs entrance to the food supply.

  12. Changes in the pharmacokinetics of digoxin in polyuria in streptozotocin-induced diabetic mice and lithium carbonate-treated mice.

    Science.gov (United States)

    Ikarashi, Nobutomo; Kagami, Mai; Kobayashi, Yasushi; Ishii, Makoto; Toda, Takahiro; Ochiai, Wataru; Sugiyama, Kiyoshi

    2011-06-01

    In humans, digoxin is mainly eliminated through the kidneys unchanged, and renal clearance represents approximately 70% of the total clearance. In this study, we used the mouse models to examine digoxin pharmacokinetics in polyuria induced by diabetes mellitus and lithium carbonate (Li(2)CO(3)) administration, including mechanistic evaluation of the contribution of glomerular filtration, tubular secretion, and tubular reabsorption. After digoxin administration to streptozotocin (STZ)-induced diabetic mice, digoxin CL/F increased to approximately 2.2 times that in normal mice. After treatment with Li(2)CO(3) (0.2%) for 10 days, the CL/F increased approximately 1.1 times for normal mice and 1.6 times for STZ mice. Creatinine clearance (CLcr) and the renal mRNA expression levels of mdr1a did not differ significantly between the normal, STZ, and Li(2)CO(3)-treated mice. The urine volume of STZ mice was approximately 26 mL/day, 22 times that of normal mice. The urine volume of Li(2)CO(3)-treated mice increased approximately 7.3 times for normal mice and 2.3 times for STZ mice. These results suggest that the therapeutic effect of digoxin may be significantly reduced in the presence of polyuria either induced by diabetes mellitus or manifested as an adverse effect of Li(2)CO(3) in diabetic patients, along with increased urine volume.

  13. Inner ear dysfunction in caspase-3 deficient mice

    Directory of Open Access Journals (Sweden)

    Woo Minna

    2011-10-01

    Full Text Available Abstract Background Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/- mouse strain. Results Average ABR thresholds of Casp3-/- mice were significantly elevated (P Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers. Conclusions These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule.

  14. C4.4A gene ablation is compatible with normal epidermal development and causes modest overt phenotypes

    DEFF Research Database (Denmark)

    Kriegbaum, Mette Camilla; Jacobsen, Benedikte; Füchtbauer, Annette

    2016-01-01

    of C4.4A in normal physiology and cancer progression. The unchallenged C4.4A-deficient mice were viable, fertile, born in a normal Mendelian distribution and, surprisingly, displayed normal development of squamous epithelia. The C4.4A-deficient mice were, nonetheless, significantly lighter than...

  15. Comparison of PBDE congener profiles and concentration levels in human specimens from China and the US and identification of human exposure sources

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In an effort to investigate the status of human exposure to PBDEs in China,available monitoring data in human specimens(including breast milk,serums,and blood) was collected from the general population as well as specific groups that are occupationally exposed.PBDEs exposure profiles and concentration levels were compared with their counterparts in the United States of America.It was found that PBDE burdens in general Chinese population are one order lower and have different congener profiles from that in the US,showing higher percentages of BDE-28 or BDE-153 in human specimens from China.Workers and residents in electronic wastes recycling regions or areas of commercial PBDE manufacturing have the highest PBDE exposure levels reported worldwide,which are close or higher than the exposure levels of the general population in the US. Highly brominated congeners,such as BDE-207 and 209,are among the major PBDE congeners,and BDE-209 has the highest percentage(above 50%) for all occupational populations studied.Principal components analysis(PCA) demonstrates that the exposure of the general population in the US is closely related to penta-BDE while the human burden in China is not.The PBDE in indoor air(gas phase) in the US is highly correlated with the PBDE burden in the general population in the US,indicating a major exposure pathway.For the occupationally exposed populations in China,the congener profiles are closely related to the commercial deca-BDE products.Examination of exposure profiles for general and occupational populations in China suggests that it is essential to include more highly brominated congeners,such as BDE-207 and 209,in future human exposure studies,in order to assess the real burdens and profiles of PBDEs exposure in China.Strict pollution prevention and occupational protection procedures are in need in China to avoid the PBDE contamination problem that has occurred in the US.

  16. Effects of different soybean milk on the health of mice fed with normal and high -fat diets%不同豆浆饮品对普通及高脂饲料饲喂小鼠健康的影响

    Institute of Scientific and Technical Information of China (English)

    张莉; 刘珊; 赵丽芹; 李怡然; 婷婷; 赵明久; 綦文涛; 李爱科

    2015-01-01

    研究普通日粮和高脂饲料条件下不同豆浆饮品对小鼠健康的影响。采用4种不同豆浆饮品(自磨非转基因豆浆 F、自磨转基因豆浆 G、两种常见市售豆浆 K 和 M)灌胃 C57小鼠,并分别饲喂普通日粮和高脂饲料,10周后处死,测定其体重增长率、肝脏系数和结肠长度等参数,并用生化分析仪测定小鼠血清葡萄糖(Glucose ,GLU)、甘油三脂(Triglycerides,TG)、总胆固醇(total choles-terol ,CHOL)、高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL -C)和低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL -C)等指标。用不同豆浆处理人结肠癌细胞 HCT-116,检测其对细胞增殖和脂滴积累的影响。结果显示,所有豆浆都不同程度地降低了小鼠血液TG,且市售豆浆 M还降低了小鼠血液 GLU 和 CHOL 浓度;豆浆处理后结肠癌细胞增殖活性得到明显抑制,但是对油酸诱导的细胞增殖和脂滴积累影响不显著。不同豆浆由于营养及功能活性物质的含量不同,对小鼠血糖、血脂和胆固醇等参数的影响不同,市售豆浆相对自磨豆浆更利于减轻高脂饲料带来的健康副作用。%The effects of different kinds of soybean milk on mice under normal diet and high fat feed con-ditions were researched.Four different kinds of soybean milk,including non -transgenic home -made soybean milk F,transgenic home -made soybean milk G and two kinds of common commercial ready -made soybean milk K and M,were selected to feed the C57 mice by gavage.Normal and high -fat diets were added,respectively.The executions were performed after 10 weeks.The weight growth rate,liver coefficient and colon length of the mice were measured.The concentrations of GLU,TG,CHOL,HDL -C and LDL -C in mice serum were determined by a biochemical analyzer.Human colon cancer cell line HCT -116 was used to investigate the influences of

  17. Normalization in econometrics

    OpenAIRE

    Hamilton, James D.; Daniel F. Waggoner; Zha, Tao

    2004-01-01

    The issue of normalization arises whenever two different values for a vector of unknown parameters imply the identical economic model. A normalization does not just imply a rule for selecting which point, among equivalent ones, to call the maximum likelihood estimator (MLE). It also governs the topography of the set of points that go into a small-sample confidence interval associated with that MLE. A poor normalization can lead to multimodal distributions, disjoint confidence intervals, and v...

  18. Normal cognitive aging.

    Science.gov (United States)

    Harada, Caroline N; Natelson Love, Marissa C; Triebel, Kristen L

    2013-11-01

    Even those who do not experience dementia or mild cognitive impairment may experience subtle cognitive changes associated with aging. Normal cognitive changes can affect an older adult's everyday function and quality of life, and a better understanding of this process may help clinicians distinguish normal from disease states. This article describes the neurocognitive changes observed in normal aging, followed by a description of the structural and functional alterations seen in aging brains. Practical implications of normal cognitive aging are then discussed, followed by a discussion of what is known about factors that may mitigate age-associated cognitive decline.

  19. Normalizers of Irreducible Subfactors

    CERN Document Server

    Smith, Roger R; Wiggins, Alan D

    2007-01-01

    We consider normalizers of an irreducible inclusion $N\\subseteq M$ of $\\mathrm{II}_1$ factors. In the infinite index setting an inclusion $uNu^*\\subseteq N$ can be strict, forcing us to also investigate the semigroup of one-sided normalizers. We relate these normalizers of $N$ in $M$ to projections in the basic construction and show that every trace one projection in the relative commutant $N'\\cap $ is of the form $u^*e_Nu$ for some unitary $u\\in M$ with $uNu^*\\subseteq N$. This enables us to identify the normalizers and the algebras they generate in several situations. In particular each normalizer of a tensor product of irreducible subfactors is a tensor product of normalizers modulo a unitary. We also examine normalizers of irreducible subfactors arising from subgroup--group inclusions $H\\subseteq G$. Here the normalizers are the normalizing group elements modulo a unitary from $L(H)$. We are also able to identify the finite trace $L(H)$-bimodules in $\\ell^2(G)$ as double cosets which are also finite union...

  20. Mice Drawer System

    Science.gov (United States)

    Cancedda, Ranieri

    2008-01-01

    differentiation factor that is normally expressed in cartilage; it can stimulate the proliferation and differentiation of human osteoprogenitor cells (cell that differentiate into an osteoblast) in vitro. The Mice Drawer System will study the effects of microgravity on transgenic mouse bones in order to identify genetic mechanisms playing a role in the reduction of the bone mass observed in humans and animals as a consequence of long-duration (greater than 100 days) microgravity exposure. Onboard the ISS, MDS is relatively self-sufficient; a crewmember will check the health status of the rodents on a daily basis, by assessing them through the viewing window. Water levels will be assessed by the crew daily and refilled as needed. Replacement of the food bars and replacement of the waste filters will be conducted inflight by crewmembers every 20-days.

  1. Behavioral analysis of relaxin-3 deficient mice.

    Science.gov (United States)

    Tanaka, Masaki; Furube, Eriko; Aoki, Miku; Watanabe, Yoshihisa

    2013-01-01

    Relaxin-3 is a neuropeptide belonging to the relaxin/insulin superfamily. Studies using rodents have revealed that relaxin-3 is predominantly expressed in neurons in the nucleus incertus of the pons, projecting axons to forebrain regions including the hypothalamus. There is evidence that relaxin-3 is involved in several functions, including food intake and stress responses. We generated relaxin-3 gene knockout (KO) mice and examined them using a battery of behavioral