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5. miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence

Author

Yu, Y., Scheel, T. K. H., Luna, J. M., Chung, H., Nishiuchi, E., Scull, M. A., Echeverría Chagas, Natalia, Ricardo-Lax, I., Kapoor, A., Lipkin, I. W., Divers, T. J., Antczak, D. F., Tennant, B. C., Rice, C. M., Yu Y., Scheel T.K.H., Luna J.M., Chung H., Nishiuchi E., Scull M.A., Echeverría Chagas Natalia, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares, Ricardo-Lax I., Kapoor A., Lipkin I.W., Divers T.J., Antczak D.F., Tennant B.C., and Rice C.M.

Subjects
Carcinoma Hepatocellular, MicroRNAs, HCC tissues
Abstract

Hepatitis C virus (HCV) requires the liver specific micro-RNA (miRNA), miR-122, to replicate. This was considered unique among RNA viruses until recent discoveries of HCV-related hepaciviruses prompting the question of a more general miR-122 dependence. Among hepaciviruses, the closest known HCV relative is the equine non-primate hepacivirus (NPHV). Here, we used Argonaute cross-linking immunoprecipitation (AGO-CLIP) to confirm AGO binding to the single predicted miR-122 site in the NPHV 5’UTR in vivo. To study miR-122 requirements in the absence of NPHV-permissive cell culture systems, we generated infectious NPHV/HCV chimeric viruses with the 5’ end of NPHV replacing orthologous HCV sequences. These chimeras were viable even in cells lacking miR-122, although miR-122 presence enhanced virus production. No other miRNAs bound this region. By random mutagenesis, we isolated HCV variants partially dependent on miR-122 as well as robustly replicating NPHV/HCV variants completely independent of any miRNAs. These miRNA independent variants even replicate and produce infectious particles in non-hepatic cells after exogenous delivery of apolipoprotein E (ApoE). Our findings suggest that miR-122 independent HCV and NPHV variants have arisen and been sampled during evolution, yet miR-122 dependence has prevailed. We propose that hepaciviruses may use this mechanism to guarantee liver tropism and exploit the tolerogenic liver environment to avoid clearance and promote chronicity.

Published
2017

9. Seasonal changes in serum leptin, food intake, and body weight in photoentrained woodchucks

Author

CONCANNON, P., LEVAC, K., RAWSON, R., TENNANT, B., and BENSADOUN, A.

Subjects
Adipose tissues -- Research, Body weight -- Research, Marmots -- Physiological aspects, Biological rhythms -- Research, Biological sciences
Abstract

Concannon, P., K. Levac, R. Rawson, B. Tennant, and A. Bensadoun. Seasonal changes in serum leptin, food intake, and body weight in photoentrained woodchucks. Am J Physiol Regulatory Integrative Comp Physiol 281: R951-R959, 2001.--Male woodchucks (Marmota monax) were maintained in northern vs. southern hemisphere photoperiods, provided feed and water ad libitum, and evaluated every 2 wk for 23 mo for body weight, absolute and relative food intake, body temperature, serum testosterone, and serum concentrations of leptin measured using an anti-mouse leptin enzyme-linked immunoassay. During late spring and summer, body weight increased 56 [+ or -] 4% above winter nadirs, and during the autumn and early winter weights decreased 27 to 43% below midsummer maxima. Serum leptin initially increased during increases in body weight, in the late spring, reached peak values (490 [+ or -] 32 pg/ml) in summer during the initial decline in body weight, and later decreased along with body weight to reach basal values (20 [+ or -] 5 pg/ml) in late winter. Spontaneous declines in food intakes in summer began 2-6 wk before resulting declines in body weight and occurred during increases in leptin [is greater than] 100 pg/ml. The rate of decline in food intakes was greatest when serum leptin was at or near peak values. Food intake increased in late winter when leptin was low and 7-10 wk before resulting increases in body weight. Testis recrudescence occurred when leptin was declining to near basal levels. The results suggest that leptin is involved in the hormonal regulation of the circannual cycle in the drive for voluntary food intake in this species. adipose; seasonality; annual cycles; photoperiod; circannual

Published
2001

11. 2402 Sorafenib (SOR) dose reduction attenuates its immunosuppressive effects and delays hepatocellular cancer (HCC) development in the woodchuck model of hepatitis B related HCC

Author

Iyer, R., primary, Patel, P., additional, Buitrago, S., additional, Curtin, L., additional, Fetterly, G., additional, Maguire, O., additional, Minderman, H., additional, Toshkov, I., additional, Tennant, B., additional, Hutson, A., additional, and Johnson, C., additional

Published
2015
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13. Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy.

Author

O'Toole, J.F., Liu, Y., Davis, E.E., Westlake, C.J., Attanasio, M., Otto, E.A., Seelow, D., Nurnberg, G., Becker, C., Nuutinen, M., Karppa, M., Ignatius, J., Uusimaa, J., Pakanen, S., Jaakkola, E., Heuvel, L.P.W.J. van den, Fehrenbach, H., Wiggins, R., Goyal, M., Zhou, W., Wolf, M.T., Wise, E., Helou, J., Allen, S.J., Murga-Zamalloa, C.A., Ashraf, S., Chaki, M., Heeringa, S., Chernin, G., Hoskins, B.E., Chaib, H., Gleeson, J., Kusakabe, T., Suzuki, T., Isaac, R.E., Quarmby, L.M., Tennant, B., Fujioka, H., Tuominen, H., Hassinen, I., Lohi, H., Houten, J.L. van, Rotig, A., Sayer, J.A., Rolinski, B., Freisinger, P., Madhavan, S.M., Herzer, M., Madignier, F., Prokisch, H., Nurnberg, P., Jackson, P.K., Khanna, H., Katsanis, N., Hildebrandt, F., O'Toole, J.F., Liu, Y., Davis, E.E., Westlake, C.J., Attanasio, M., Otto, E.A., Seelow, D., Nurnberg, G., Becker, C., Nuutinen, M., Karppa, M., Ignatius, J., Uusimaa, J., Pakanen, S., Jaakkola, E., Heuvel, L.P.W.J. van den, Fehrenbach, H., Wiggins, R., Goyal, M., Zhou, W., Wolf, M.T., Wise, E., Helou, J., Allen, S.J., Murga-Zamalloa, C.A., Ashraf, S., Chaki, M., Heeringa, S., Chernin, G., Hoskins, B.E., Chaib, H., Gleeson, J., Kusakabe, T., Suzuki, T., Isaac, R.E., Quarmby, L.M., Tennant, B., Fujioka, H., Tuominen, H., Hassinen, I., Lohi, H., Houten, J.L. van, Rotig, A., Sayer, J.A., Rolinski, B., Freisinger, P., Madhavan, S.M., Herzer, M., Madignier, F., Prokisch, H., Nurnberg, P., Jackson, P.K., Khanna, H., Katsanis, N., and Hildebrandt, F.

Abstract

Contains fulltext : 88043.pdf (publisher's version ) (Closed access), The autosomal recessive kidney disease nephronophthisis (NPHP) constitutes the most frequent genetic cause of terminal renal failure in the first 3 decades of life. Ten causative genes (NPHP1-NPHP9 and NPHP11), whose products localize to the primary cilia-centrosome complex, support the unifying concept that cystic kidney diseases are "ciliopathies". Using genome-wide homozygosity mapping, we report here what we believe to be a new locus (NPHP-like 1 [NPHPL1]) for an NPHP-like nephropathy. In 2 families with an NPHP-like phenotype, we detected homozygous frameshift and splice-site mutations, respectively, in the X-prolyl aminopeptidase 3 (XPNPEP3) gene. In contrast to all known NPHP proteins, XPNPEP3 localizes to mitochondria of renal cells. However, in vivo analyses also revealed a likely cilia-related function; suppression of zebrafish xpnpep3 phenocopied the developmental phenotypes of ciliopathy morphants, and this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal. Consistent with a role for XPNPEP3 in ciliary function, several ciliary cystogenic proteins were found to be XPNPEP3 substrates, for which resistance to N-terminal proline cleavage resulted in attenuated protein function in vivo in zebrafish. Our data highlight an emerging link between mitochondria and ciliary dysfunction, and suggest that further understanding the enzymatic activity and substrates of XPNPEP3 will illuminate novel cystogenic pathways.

Published
2010

14. Antiviral activity of a conjugate of adenine-9-beta-D-arabinofuranoside 5'-monophosphate and a 9 kDa fragment of arabinogalactan

Author

Josephson L, Jv, Rutkowski, Paul K, Timothy Frigo, Be, Korba, Tennant B, and Ev, Groman

Subjects
Molecular Weight, Hepatitis B virus, Marmota, DNA, Viral, Animals, Hepatitis B Virus, Woodchuck, Antiviral Agents, Galactans, Vidarabine Phosphate
Abstract

An arabinogalactan conjugate containing a 9 kDa fragment of arabinogalactan and adenine-9-beta-D-arabinofuranoside 5'-monophosphate (araAMP), denoted AG(9 kDa)-araAMP, has been synthesized and characterized. In 2.2.15 (human hepatoblastoma) cells, the attachment of araAMP to AG(9 kDa), a ligand of the asialoglycoprotein receptor, decreased the effective concentration for inhibiting extracellular hepatitis B virus (HBV) production by 90% (EC90) from 17 to 0.9 microM adenine arabinoside (araA) equivalents, and increased the cytotoxic concentration (CC50) from 188 to17 300 microM araA equivalents. Hence, the selectivity index (CC50/EC90) of araA was improved from 11 (188/17) to19200 (17 300/0.9) by conjugation with the 9 kDa fragment of arabinogalactan. AG(9 kDa)-araAMP did not affect the production of viral RNA or viral proteins. In the woodchuck hepatitis model, AG(9 kDa)-araAMP inhibited woodchuck hepatitis virus (WHV) DNA replication at a dose of 0.3 mg of araA equivalents per kg; in this case, AG(9 kDa)-araAMP was 20-30 times more potent than was unconjugated araA. AG(9 kDa)-araAMP was effective by intramuscular or subcutaneous administration. The reduction in HBV DNA levels obtained in 2.2.15 cells and of WHV DNA levels in woodchucks was sustained after treatment with AG(9 kDa)-araAMP ceased. In both cases, viral DNA gradually returned to pre-treatment levels.

Published
1996

15. Identification and analysis of murine pancreatic islet enhancers

Author

Tennant, B. R., primary, Robertson, A. G., additional, Kramer, M., additional, Li, L., additional, Zhang, X., additional, Beach, M., additional, Thiessen, N., additional, Chiu, R., additional, Mungall, K., additional, Whiting, C. J., additional, Sabatini, P. V., additional, Kim, A., additional, Gottardo, R., additional, Marra, M. A., additional, Lynn, F. C., additional, Jones, S. J. M., additional, Hoodless, P. A., additional, and Hoffman, B. G., additional

Published
2012
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16. CO2-Soluble, Nonionic, Water-Soluble Surfactants That Stabilize CO2-in-Brine Foams

Author

Xing, D.., primary, Wei, B.., additional, McLendon, W.., additional, Enick, R.., additional, McNulty, S.., additional, Trickett, K.., additional, Mohamed, A.., additional, Cummings, S.., additional, Eastoe, J.., additional, Rogers, S.., additional, Crandall, D.., additional, Tennant, B.., additional, McLendon, T.., additional, Romanov, V.., additional, and Soong, Y.., additional

Published
2012
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18. Boxer colitis

Author

Edward Hall, Tennant, B. J., Payne-Johnson, C. E., and Kelly, D. F.

Subjects
Dogs, General Veterinary, Animals, Colitis, Ulcerative, General Medicine, Dog Diseases, United Kingdom
Published
1992

49. Boxer colitis

Author

Hall, E., primary, Tennant, B., additional, Payne-Johnson, C., additional, and Kelly, D., additional

Published
1992
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50. C02-Soluble, Nonionic, Water-Soluble Surfactants That Stabilize C02-in-Brine Foams.

Author

Xing, D., Wei, B., McLendon, W., Enick, R., McNulty, S., Trickett, K., Mohamed, A., Cummings, S., Eastoe, J., Rogers, S., Crandall, D., Tennant, B., McLendon, T., Romanov, V., and Soong, Y.

Subjects
CARBON dioxide solubility, SURFACE active agents, FOAM, SALT, NEUTRON scattering, SANDSTONE, TOMOGRAPHY, POLYSTYRENE
Abstract

The article presents a research whose aim was to determine the carbon dioxide (CO2) solubility of commercially available surfactants and to assess their ability to generate C02-in-brine foams using foam-stability tests in windowed cells, to assess the foam structure in a windowed cell using high-pressure small-angle-neutron-scattering (HP SANS), to measure transient mobility using Berea sandstone and computed-tomography (CT) imaging of C02 foams in brine-saturated polystyrene cores.

Published
2012
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