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Sample records for woodchuck marmota monax

  1. Transcriptome Analysis and Comparison of Marmota monax and Marmota himalayana.

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    Yanan Liu

    Full Text Available The Eastern woodchuck (Marmota monax is a classical animal model for studying hepatitis B virus (HBV infection and hepatocellular carcinoma (HCC in humans. Recently, we found that Marmota himalayana, an Asian animal species closely related to Marmota monax, is susceptible to woodchuck hepatitis virus (WHV infection and can be used as a new mammalian model for HBV infection. However, the lack of genomic sequence information of both Marmota models strongly limited their application breadth and depth. To address this major obstacle of the Marmota models, we utilized Illumina RNA-Seq technology to sequence the cDNA libraries of liver and spleen samples of two Marmota monax and four Marmota himalayana. In total, over 13 billion nucleotide bases were sequenced and approximately 1.5 billion clean reads were obtained. Following assembly, 106,496 consensus sequences of Marmota monax and 78,483 consensus sequences of Marmota himalayana were detected. For functional annotation, in total 73,603 Unigenes of Marmota monax and 78,483 Unigenes of Marmota himalayana were identified using different databases (NR, NT, Swiss-Prot, KEGG, COG, GO. The Unigenes were aligned by blastx to protein databases to decide the coding DNA sequences (CDS and in total 41,247 CDS of Marmota monax and 34,033 CDS of Marmota himalayana were predicted. The single nucleotide polymorphisms (SNPs and the simple sequence repeats (SSRs were also analyzed for all Unigenes obtained. Moreover, a large-scale transcriptome comparison was performed and revealed a high similarity in transcriptome sequences between the two marmota species. Our study provides an extensive amount of novel sequence information for Marmota monax and Marmota himalayana. This information may serve as a valuable genomics resource for further molecular, developmental and comparative evolutionary studies, as well as for the identification and characterization of functional genes that are involved in WHV infection and HCC

  2. The Skeletal Biology of Hibernating Woodchucks (Marmota monax)

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    Doherty, Alison H.

    Long periods of inactivity in most mammals lead to significant bone loss that may not be completely recovered during an individual's lifetime regardless of future activity. Extended bouts of inactivity are the norm for hibernating mammals. It remains largely unknown, however, how these animals avoid adversely affecting bone, their quality, and ultimately survival given the challenges posed to their skeletons by inactivity and nutritional deprivation during hibernation. The primary goal of this project was to identify the physiological mechanisms regulating bone density, area and strength during extended periods of annual inactivity in hibernating woodchucks (Marmota monax). The overall hypothesis that bone integrity is unaffected by several months of inactivity during hibernation in woodchucks was tested across multiple levels of biological function. To gain a holistic assessment of seasonal bone integrity, the locomotor behavior and estimated stresses acting on woodchuck bones were investigated in conjunction with computed tomography scans and three-point bending tests to determine bone density, geometry, and mechanical properties of the long bones throughout the year. In addition, serum protein expression was examined to ascertain bone resorption and formation processes indicative of overall annual skeletal health. It was determined that woodchucks avoid significant changes in gait preference, but experience a decrease in bending stresses acting on distal limb bones following hibernation. Computed tomography scans indicated that bone mass, distribution, and trabecular structure are maintained in these animals throughout the year. Surprisingly, cortical density increased significantly posthibernation. Furthermore, three-point bending tests revealed that although less stiff, woodchuck femora were just as tough during the hibernation season, unlike brittle bones associated with osteoporosis. Finally, bone serum markers suggested a net maintenance of bone resorption

  3. Experimental infection of Marmota monax with a novel hepatitis A virus.

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    Yu, Jie-Mei; Li, Li-Li; Xie, Guang-Cheng; Zhang, Cui-Yuan; Ao, Yuan-Yun; Duan, Zhao-Jun

    2018-05-01

    To establish an animal model for the newly identified Marmota Himalayana hepatovirus, MHHAV, so as to develop a better understanding of the infection of hepatitis A viruses. Five experimental woodchucks (Marmota monax) were inoculated intravenously with the purified MHHAV from wild woodchuck feces. One animal injected with PBS was defined as a control. Feces and blood were routinely collected. After the animals were subjected to necropsy, different tissues were collected. The presence of viral RNA and negative sense viral RNA was analyzed in all the samples and histopathological and in situ hybridization analysis was performed for the tissues. MHHAV infection caused fever but no severe symptoms or death. Virus was shed in feces beginning at 2 dpi, and MHHAV RNA persisted in feces for ~2 months, with a biphasic increase, and in blood for ~30 days. Viral RNA was detected in all the tissues, with high levels in the liver and spleen. Negative-strand viral RNA was detected only in the liver. Furthermore, the animals showed histological signs of hepatitis at 45 dpi. MHHAV can infect M. monax and is associated with hepatic disease. Therefore, this animal can be used as a model of HAV pathogenesis and to evaluate antiviral and anticancer therapeutics.

  4. Environmental Statement, Oswego Steam Station, Unit Six.

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    1973-03-29

    Tamias striatus) muskrat (Ondatra zibethicus) woodchuck (Marmota monax) Rept ile s eastern painted turtle (Chrysemys pi~cta) Amphibians grass frog (Rana...Terrestrial Ecoloqy The analysis presented on terrestrial ecology is somewhat nebulous due to the fact that the location of the generating facility is in...The analysis presented on terrestrial ecology is somewhat nebulous due to the - fact that the location of the generating facility is in an industrial

  5. Radioimmunoassay and characterization of woodchuck hepatitis virus core antigen and antibody

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    Ponzetto, A; Cote, P J; Ford, E C; Engle, R; Gerin, J L; Cicmanec, J; Shapiro, M; Purcell, R H

    1985-06-01

    Solid-phase radioimmunoassays for woodchuck hepatitis virus core antigen (WHcAg) and antibody (anti-WHc) were developed. WHcAg in woodchuck liver homogenates was characterized by ultracentrifugation in CsCl gradients; both heavy and light cores were obtained from the liver of an animal during acute WHV infection, which is consistent with observations in hepatitis B virus infection in man. Endpoint titers of anti-WHc were higher in chronic WHV carriers than in animals recovered from acute infections. Both IgM and IgG anti-WHc antibodies were produced by infected woodchucks. A survey of colony woodchucks demonstrated that 88/89 animals having one or more markers of past or ongoing WHV infection were positive for anti-WHc. Thus, serum anti-WHc appears to be a sensitive marker of WHV infection.

  6. Cross-species hybridization of woodchuck hepatitis virus-induced hepatocellular carcinoma using human oligonucleotide microarrays

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    Paul W Anderson; Bud C Tennant; Zhenghong Lee

    2006-01-01

    AIM: To demonstrate the feasibility of using woodchuck samples on human microarrays, to provide insight into pathways involving positron emission tomography (PET) imaging tracers and to identify genes that could be potential molecular imaging targets for woodchuck hepatocellular carcinoma.METHODS: Labeled cRNA from woodchuck tissue samples were hybridized to Affymetrix U133 plus 2.0 GeneChips(R). Ten genes were selected for validation using quantitative RT-PCR and literature review was made.RESULTS: Testis enhanced gene transcript (BAX Inhibitor 1), alpha-fetoprotein, isocitrate dehydrogenase 3 (NAD+) beta, acetyl-CoA synthetase 2, carnitine palmitoyltransferase 2, and N-myc2 were up-regulated and spermidine/spermine N1-acetyltransferase was down-regulated in the woodchuck HCC. We also found previously published results supporting 8 of the 10 most up-regulated genes and all 10 of the 10 most downregulated genes.CONCLUSION: Many of our microarray results were validated using RT-PCR or literature search. Hence, we believe that woodchuck HCC and non-cancerous liver samples can be used on human microarrays to yield meaningful results.

  7. Spliced RNA of woodchuck hepatitis virus.

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    Ogston, C W; Razman, D G

    1992-07-01

    Polymerase chain reaction was used to investigate RNA splicing in liver of woodchucks infected with woodchuck hepatitis virus (WHV). Two spliced species were detected, and the splice junctions were sequenced. The larger spliced RNA has an intron of 1300 nucleotides, and the smaller spliced sequence shows an additional downstream intron of 1104 nucleotides. We did not detect singly spliced sequences from which the smaller intron alone was removed. Control experiments showed that spliced sequences are present in both RNA and DNA in infected liver, showing that the viral reverse transcriptase can use spliced RNA as template. Spliced sequences were detected also in virion DNA prepared from serum. The upstream intron produces a reading frame that fuses the core to the polymerase polypeptide, while the downstream intron causes an inframe deletion in the polymerase open reading frame. Whereas the splicing patterns in WHV are superficially similar to those reported recently in hepatitis B virus, we detected no obvious homology in the coding capacity of spliced RNAs from these two viruses.

  8. Streptococcus himalayensis sp. nov., isolated from the respiratory tract of Marmota himalayana.

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    Niu, Lina; Lu, Shan; Lai, Xin-He; Hu, Shoukui; Chen, Cuixia; Zhang, Gui; Yang, Jing; Jin, Dong; Wang, Yi; Lan, Ruiting; Lu, Gang; Xie, Yingping; Ye, Changyun; Xu, Jianguo

    2017-02-01

    Five strains of Gram-positive-staining, catalase-negative, coccus-shaped, chain-forming organisms isolated separately from the respiratory tracts of five Marmota himalayana animals in the Qinghai-Tibet Plateau of China were subjected to phenotypic and molecular taxonomic analyses. Comparative analysis of the 16S rRNA gene indicated that these singular organisms represent a new member of the genus Streptococcus, being phylogenetically closest to Streptococcus marmotae DSM 101995T (98.4 % similarity). The groEL, sodA and rpoB sequence analysis showed interspecies similarity values between HTS2T and Streptococcus. marmotae DSM 101995T, its closest phylogenetic relative based on 16S rRNA gene sequences, of 98.2, 78.8 and 93.7 %, respectively. A whole-genome phylogenetic tree built from 82 core genes of genomes from 16 species of the genus Streptococcus validated that HTS2T forms a distinct subline and exhibits specific phylogenetic affinity with S. marmotae. In silico DNA-DNA hybridization of HTS2T showed an estimated DNA reassociation value of 40.5 % with Streptococcus. marmotae DSM 101995T. On the basis of their phenotypic characteristics and phylogenetic findings, it is proposed that the five isolates be classified as representatives of a novel species of the genus Streptococcus, Streptococcus himalayensis sp. nov. The type strain is HTS2T (=DSM 101997T=CGMCC 1.15533T). The genome of Streptococcus himalayensis sp. nov. strain HTS2T contains 2195 genes with a size of 2 275 471 bp and a mean DNA G+C content of 41.3 mol%.

  9. The hybrid EIA test: a specific and sensitive assay for the detection of woodchuck antibody to hepatitis surface antigen (anti-WHs).

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    Millman, I; Glass, R G

    1988-05-01

    'Ausria II' polystyrene beads (Abbott Labs, N. Chicago) are reacted with woodchuck serum positive for WHsAg in a dilution predetermined by titration. This modified bead is used in a blocking assay to detect the presence of antibody to the surface antigen of woodchuck hepatitis virus (anti-WHs). Serum containing woodchuck anti-WHs and commercial horseradish peroxidase (HRP) labeled anti-HBs are sequentially added. A drop in optical density at 492 nm of 50% or more due to the blocking of HRP conjugated anti-HBs by anti-WHs compared with a control (negative woodchuck serum) is a measure of anti-WHs. The ease and simplicity of converting readily available 'Ausria II' beads to specific reagents for detecting anti-WHs should be welcomed by investigators studying WHV. The method described is both sensitive and reproducible.

  10. Novel Hepatozoon in vertebrates from the southern United States.

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    Allen, Kelly E; Yabsley, Michael J; Johnson, Eileen M; Reichard, Mason V; Panciera, Roger J; Ewing, Sidney A; Little, Susan E

    2011-08-01

    Novel Hepatozoon spp. sequences collected from previously unrecognized vertebrate hosts in North America were compared with documented Hepatozoon 18S rRNA sequences in an effort to examine phylogenetic relationships between the different Hepatozoon organisms found cycling in nature. An approximately 500-base pair fragment of 18S rDNA common to Hepatozoon spp. and some other apicomplexans was amplified and sequenced from the tissues or blood of 16 vertebrate host species from the southern United States, including 1 opossum (Didelphis virginiana), 2 bobcats (Lynx rufus), 1 domestic cat (Felis catus), 3 coyotes (Canis latrans), 1 gray fox (Urocyon cinereoargenteus), 4 raccoons (Procyon lotor), 1 pet boa constrictor (Boa constrictor imperator), 1 swamp rabbit (Sylvilagus aquaticus), 1 cottontail rabbit (Sylvilagus floridanus), 4 woodrats (Neotoma fuscipes and Neotoma micropus), 3 white-footed mice (Peromyscus leucopus), 8 cotton rats (Sigmodon hispidus), 1 cotton mouse (Peromyscus gossypinus), 1 eastern grey squirrel (Sciurus carolinensis), and 1 woodchuck (Marmota monax). Phylogenetic analyses and comparison with sequences in the existing database revealed distinct groups of Hepatozoon spp., with clusters formed by sequences obtained from scavengers and carnivores (opossum, raccoons, canids, and felids) and those obtained from rodents. Surprisingly, Hepatozoon spp. sequences from wild rabbits were most closely related to sequences obtained from carnivores (97.2% identical), and the sequence from the boa constrictor was most closely related to the rodent cluster (97.4% identical). These data are consistent with recent work identifying prey-predator transmission cycles in Hepatozoon spp. and suggest this pattern may be more common than previously recognized.

  11. In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus.

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    Lew, Y Y; Michalak, T I

    2001-02-01

    Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity was tested in susceptible animals. Applying PCR-based assays discriminating between the total pool of WHV genomes and covalently closed circular DNA (cccDNA), combined with enzymatic elimination of extracellular viral sequences potentially associated with the cell surface, our study documents that virus replicating in woodchuck lymphoid cells is infectious to homologous hepatocytes and lymphoid cells in vitro. The productive replication of WHV from lymphoid cells in cultured hepatocytes was evidenced by the appearance of virus-specific DNA, cccDNA, and antigens, transmissibility of the virus through multiple passages in hepatocyte cultures, and the ability of the passaged virus to infect virus-naive animals. The data also revealed that WHV from lymphoid cells can initiate classical acute viral hepatitis in susceptible animals, albeit small quantities (approximately 10(3) virions) caused immunovirologically undetectable (occult) WHV infection that engaged the lymphatic system but not the liver. Our results provide direct in vitro and in vivo evidence that lymphoid cells in the infected host support propagation of infectious hepadnavirus that has the potential to induce hepatitis. They also emphasize a principal role of the lymphatic system in the maintenance and dissemination of hepadnavirus infection, particularly when infection is induced by low virus doses.

  12. Alimentazione di Marmota marmota in praterie altimontane delle dolomiti bellunesi

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    Alessandro Rudatis

    2006-03-01

    Full Text Available Abstract The diet of Marmota marmota in the mountain prairie of south-eastern Italian Alps. Diet composition of two family groups of alpine marmots was investigated in two areas of the Agordino’s Dolomites (Italian Alps in June-September 2001, by means of microscopic analysis of faeces and of direct observation of feeding activity. During the whole period of activity, a high consume of Angiosperms was confirmed, especially plants in flower; among them the “graminoids” seemed to play an important role only during the initial part of the active period. Generally vegetative parts predominated over flowers. The ingestion of animal preys was not confirmed by the analysis of droppings. Comparing diet composition of the two groups, Graminaceae (Poa, Phleum, Compositae (Achillea, Cyperaceae/Juncaceae, Leguminosae (Anthyllis, Rosaceae, and Labiatae (Prunella, Stachys formed the bulk of marmot diet in the study areas. Diet showed low diversity considering the abundance of plant species in the surrounding environment. Food resources were probably used in relation to their easy digestibility, with a high content in proteins, sugar and water. The knowledge of vegetation features in relation to marmot trophic habits can represent a useful tool for the management of this species. Riassunto Il regime alimentare di due gruppi di Marmotta alpina è stato studiato in giugno-settembre 2001 in due aree delle Dolomiti agordine (SE Italia, attraverso l’analisi microscopica delle feci e l’osservazione diretta dell’attività alimentare. Durante tutto il periodo di attività si è notato un forte consumo di Angiosperme, specialmente piante a fiore, mentre le ”graminoidi” sembra giochino un ruolo importante all’inizio della stagione. In generale le parti vegetali predominano sui fiori. L’ingestione di prede animali non è stata

  13. THE LIVER OF WOODCHUCKS CHRONICALLY INFECTED WITH THE WOODCHUCK HEPATITIS VIRUS CONTAINS FOCI OF VIRUS CORE ANTIGEN NEGATIVE HEPATOCYTES WITH BOTH ALTERED AND NORMAL MORPHOLOGY

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    Xu, Chunxiao; Yamamoto, Toshiki; Zhou, Tianlun; Aldrich, Carol E.; Frank, Katy; Cullen, John M.; Jilbert, Allison R.; Mason, William S.

    2007-01-01

    The livers of woodchucks chronically infected with woodchuck hepatitis virus (WHV) contain foci of morphologically altered hepatocytes (FAH) with “basophilic”, “amphophilic” and “clear cell” phenotypes, which are possibly pre-neoplastic in nature. Interestingly, most fail to express detectable levels of WHV proteins and nucleic acids. We studied sections of WHV-infected liver tissue to determine if all foci of hepatocytes that failed to express detectable levels of WHV, as assessed by immunoperoxidase staining for WHV core antigen, could be classified morphologically as FAH. We found that at least half of the foci of WHV core antigen negative hepatocytes did not show clear morphological differences in either H&E or PAS (periodic acid Schiff) stained sections from surrounding hepatocytes, and were therefore not designated as FAH. In the second approach, we assayed core antigen negative foci for the presence of fetuin B, a serum protein produced by normal hepatocytes, but not by neoplastic hepatocytes in hepatocellular carcinomas. Basophilic and amphophilic FAH had reduced levels of fetuin B compared to hepatocytes present in the surrounding liver; fetuin B staining was detected in clear cell FAH but the level could not be accurately assessed because of the displacement of fetuin B to the cell periphery by accumulated glycogen. The foci of morphologically normal WHV core antigen negative hepatocytes had similar levels of fetuin B to that of the surrounding hepatocytes. The co-existence of at least four types of WHV core antigen negative foci, including those with no obvious morphologic changes, raises the possibility that the different foci arise from distinct primary events. We hypothesize that a common event is loss of the ability to express WHV, allowing these hepatocytes to escape immune mediated cell death and to undergo clonal expansion to form distinct foci. PMID:17078989

  14. On the status of the Long-tailed Marmot Marmota caudata (Mammalia: Rodentia: Sciuridae in Kargil, Ladakh (Indian Trans-Himalaya

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    Tanveer Ahmed

    2016-08-01

    Full Text Available Two species of marmots occur in India, the Himalayan Marmot Marmota himalayana and the Long-tailed Marmot or Golden Marmot Marmota caudata.  Marmots constitute part of the diet of some globally endangered carnivores in the Trans-Himalaya, yet studies on marmots in India are scanty.  Besides, the status of the Long-tailed Marmot is still unknown in India.  Considering this, a survey was carried out in Rangdum Valley, Kargil between May and July 2011 to collect baseline information on the Long-tailed Marmot.  Trails and roads were explored through walk and slow moving vehicle, respectively.  The Long-tailed Marmot was found to have a density of 14.31±2.10 per sq.km. and an encounter rate of 2.86±0.42 per km.  Most of the observations of Long-tailed Marmot were in hilly areas (77.7%, lower slope (48.8% and herbaceous meadow (38.0%.  The current information is expected to bring concern towards this lesser known species in India.  

  15. Antiviral Efficacy and Host Innate Immunity Associated with SB 9200 Treatment in the Woodchuck Model of Chronic Hepatitis B.

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    Kyle E Korolowicz

    Full Text Available SB 9200, an oral prodrug of the dinucleotide SB 9000, is being developed for the treatment of chronic hepatitis B virus (HBV infection and represents a novel class of antivirals. SB 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I and nucleotide-binding oligomerization domain-containing protein 2 (NOD2 resulting in interferon (IFN mediated antiviral immune responses in virus-infected cells. Additionally, the binding of SB 9200 to these sensor proteins could also sterically block the ability of the viral polymerase to access pre-genomic RNA for nucleic acid synthesis. The immune stimulating and direct antiviral properties of SB 9200 were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (WHV by daily, oral dosing at 15 and 30 mg/kg for 12 weeks. Prolonged treatment resulted in 2.2 and 3.7 log10 reductions in serum WHV DNA and in 0.5 and 1.6 log10 declines in serum WHV surface antigen from pretreatment level with the lower or higher dose of SB 9200, respectively. SB 9200 treatment also resulted in lower hepatic levels of WHV nucleic acids and antigen and reduced liver inflammation. Following treatment cessation, recrudescence of viral replication was observed but with dose-dependent delays in viral relapse. The antiviral effects were associated with dose-dependent and long-lasting induction of IFN-α, IFN-β and IFN-stimulated genes in blood and liver, which correlated with the prolonged activation of the RIG-I/NOD2 pathway and hepatic presence of elevated RIG-I protein levels. These results suggest that in addition to a direct antiviral activity, SB 9200 induces antiviral immunity during chronic hepadnaviral infection via activation of the viral sensor pathway.

  16. Powassan Virus: Persistence of Virus Activity During 1966

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    McLean, Donald M.; Cobb, Cathron; Gooderham, Susan E.; Smart, Carol A.; Wilson, A. G.; Wilson, W. E.

    1967-01-01

    Powassan virus isolations were achieved from three of 60 pools of Ixodes cookei ticks removed from 286 groundhogs (Marmota monax) which were collected some 200 miles north of Toronto between May 5 and September 5, 1966. Virus yields per pool of one to 11 ticks ranged from 102.5 to 106.0 TCD50 for primary swine kidney tissue cultures, and positive pools were collected on June 24, July 15 and August 10. Powassan neutralizing antibodies were detected by mouse inoculation tests in 143 of 362 animals including 127 of 286 groundhogs, 14 of 45 red squirrels (Tamiasciurus hudsonicus) and two of 31 other forest mammals. The monthly prevalence of antibody in the current season's groundhogs increased from 0 to 25% with the progression of summer, but in older animals the incidence remained between 38 and 62% throughout the season. These results substantiate earlier findings which pointed towards the maintenance of Powassan virus in nature by a cycle involving groundhogs and squirrels as reservoirs, with ticks as vectors, from which human infections occurred tangentially. PMID:6019677

  17. Responses of high-elevation herbaceous plant assemblages to low glacial CO₂ concentrations revealed by fossil marmot (Marmota) teeth.

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    McLean, Bryan S; Ward, Joy K; Polito, Michael J; Emslie, Steven D

    2014-08-01

    Atmospheric CO2 cycles of the Quaternary likely imposed major constraints on the physiology and growth of C3 plants worldwide. However, the measured record of this remains both geographically and taxonomically sparse. We present the first reconstruction of physiological responses in a late Quaternary high-elevation herbaceous plant community from the Southern Rocky Mountains, USA. We used a novel proxy-fossilized tooth enamel of yellow-bellied marmots (Marmota flaviventris)-which we developed using detailed isotopic analysis of modern individuals. Calculated C isotopic discrimination (Δ) of alpine plants was nearly 2 ‰ lower prior to the Last Glacial Maximum than at present, a response almost identical to that of nonherbaceous taxa from lower elevations. However, initial shifts in Δ aligned most closely with the onset of the late Pleistocene bipolar temperature "seesaw" rather than CO2 increase, indicating unique limitations on glacial-age high-elevation plants may have existed due to both low temperatures and low CO2. Further development of system-specific faunal proxies can help to clarify this and other plant- and ecosystem-level responses to past environmental change.

  18. Hibernation metabolism of mammalia (marmota menzeri kaschk) and reptiles (testudo horsfieldi gray)

    International Nuclear Information System (INIS)

    Gibarova, S.

    2001-01-01

    It has been revealed that, upon hypnosis resulting from the winter hibernation, the content of glucose in the blood of mammals (Marmota menzberi Kaschk.) and reptiles( Testudo horsfieldi Gray) has decreased whereas the components of the lipid exchange and the activity of the enzyme alanin and aspartate transaminase have increased, the changes observed being more pronounced in the tortoise than in marmote. On a level of the intact organism in vitro, over the 30 fold and 100 fold decrease of gas oxygen exchange takes place in marmots and tortoises, respectively upon the body temperature decreases as low as 4-5 degree Celsius as a result of winter hibernation. At a mitochondrial level, a decrease in the bio energetic parameters by 4-6 times with a prevailing inhibition of succinate oxidation was recorded in marmots and by 3 times in tortoises in the state of hypo biosis, which witnesses deep restructuring of the enzymatic metabolic characteristics of the tissue energetics under these conditions. More significant inhibition of the respiratory activity in the mitochondria of the liver, kidney and heart against the other organs was reported in ground squirrel when in the state of natural winter sleeping. Upon the temperature drop in vitro by 37,25,16 degree Celsius the respiratory activity of the liver mitochondria of active rodents was recorded to decrease to a significantly smaller degrees ( by 4 times ) than in those of the reptiles ( by 12 times ), thus witnessing a smaller temperature dependence of the subcellular energetics of the warm blooded animals and the necessity of functioning of special mechanism decreasing mitochondrial respiration in this group as compared with the cold blooded animals while in hypo biosis

  19. Stable isotopes in yellow-bellied marmot (Marmota flaviventris) fossils reveal environmental stability in the late Quaternary of the Colorado Rocky Mountains

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    Reynard, Linda M.; Meltzer, David J.; Emslie, Steven D.; Tuross, Noreen

    2015-03-01

    High elevation plant and animal communities are considered extremely sensitive to environmental change. We investigated an exceptional fossil record of yellow-bellied marmot (Marmota flaviventris) specimens that was recovered from Cement Creek Cave (elev. 2860 m) and ranged in age from radiocarbon background circa 49.8 cal ka BP to ~ 1 cal ka BP. We coupled isotopic and radiocarbon measurements (δ18O, δD, δ15N, δ13C, and 14C) of bone collagen from individually-AMS dated specimens of marmots to assess ecological responses by this species to environmental change over time in a high elevation basin in the Rocky Mountains of southwestern Colorado, USA. We find little change in all four isotope ratios over time, demonstrating considerable environmental stability during periods when the marmots were present. The stable ecology and the apparent persistence of the small mammal community in the cave fauna throughout the late Quaternary are in marked contrast to the changes that occurred in the large mammal community, including local extirpation and extinction, at the end of the Pleistocene.

  20. Fatal combined infection with canine distemper virus and orthopoxvirus in a group of Asian marmots (Marmota caudata).

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    Origgi, F C; Sattler, U; Pilo, P; Waldvogel, A S

    2013-09-01

    A fatal combined infection with canine distemper virus (CDV) and orthopoxvirus (OPXV) in Asian marmots (Marmota caudata) is reported in this article. A total of 7 Asian marmots from a small zoological garden in Switzerland were found dead in hibernation during a routine check in the winter of 2011. The marmots died in February 2011. No clinical signs of disease were observed at any time. The viruses were detected in all individuals for which the tissues were available (n = 3). Detection of the viruses was performed by reverse transcription polymerase chain reaction. The most consistent gross lesion was a neck and thorax edema. A necrotizing pharyngitis and a multifocal necrotizing pneumonia were observed histologically. Numerous large intracytoplasmic eosinophilic inclusions were seen in the epithelial cells of the pharynx, of the airways, and in the skin keratinocytes. Brain lesions were limited to mild multifocal gliosis. Phylogenetic analysis revealed that the marmot CDV strain was closely related to the clusters of CDVs detected in Switzerland in wild carnivores during a local outbreak in 2002 and the 2009-2010 nationwide epidemic, suggesting a spillover of this virus from wildlife. The OPXV was most closely related to a strain of cowpoxvirus, a poxvirus species considered endemic in Europe. This is the first reported instance of CDV infection in a rodent species and of a combined CDV and OPXV infection.

  1. Enhancing virus-specific immunity in vivo by combining therapeutic vaccination and PD-L1 blockade in chronic hepadnaviral infection.

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    Jia Liu

    2014-01-01

    Full Text Available Hepatitis B virus (HBV persistence is facilitated by exhaustion of CD8 T cells that express the inhibitory receptor programmed cell death-1 (PD-1. Improvement of the HBV-specific T cell function has been obtained in vitro by inhibiting the PD-1/PD-ligand 1 (PD-L1 interaction. In this study, we examined whether in vivo blockade of the PD-1 pathway enhances virus-specific T cell immunity and leads to the resolution of chronic hepadnaviral infection in the woodchuck model. The woodchuck PD-1 was first cloned, characterized, and its expression patterns on T cells from woodchucks with acute or chronic woodchuck hepatitis virus (WHV infection were investigated. Woodchucks chronically infected with WHV received a combination therapy with nucleoside analogue entecavir (ETV, therapeutic DNA vaccination and woodchuck PD-L1 antibody treatment. The gain of T cell function and the suppression of WHV replication by this therapy were evaluated. We could show that PD-1 expression on CD8 T cells was correlated with WHV viral loads during WHV infection. ETV treatment significantly decreased PD-1 expression on CD8 T cells in chronic carriers. In vivo blockade of PD-1/PD-L1 pathway on CD8 T cells, in combination with ETV treatment and DNA vaccination, potently enhanced the function of virus-specific T cells. Moreover, the combination therapy potently suppressed WHV replication, leading to sustained immunological control of viral infection, anti-WHs antibody development and complete viral clearance in some woodchucks. Our results provide a new approach to improve T cell function in chronic hepatitis B infection, which may be used to design new immunotherapeutic strategies in patients.

  2. Traffics and wildlife: A preliminary study on road-kill

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    Rustiati, Elly Lestari

    2012-01-01

    This paper presents the preliminary finding on road kill survey by direct observations onthe high ways. The road-kills recorded of small wildlife, including medium size-mammal (2.50%, n =1), birds (5.00%, n = 2) and small mammals (92.50%, n = 37). The small mammals include the mostcommon mammals in the areas, squirrels, raccoons, skunks and woodchuck. Of mammals, squirrels(35.00%) were the highest recorded, followed by woodchucks (25.00%), mice/shrew (17.50%),raccoons (10.00%), skunk (5.00%) ...

  3. Insights into the evolution of pathogenicity of Escherichia coli from genomic analysis of intestinal E. coli of Marmota himalayana in Qinghai-Tibet plateau of China.

    Science.gov (United States)

    Lu, Shan; Jin, Dong; Wu, Shusheng; Yang, Jing; Lan, Ruiting; Bai, Xiangning; Liu, Sha; Meng, Qiong; Yuan, Xuejiao; Zhou, Juan; Pu, Ji; Chen, Qiang; Dai, Hang; Hu, Yuanyuan; Xiong, Yanwen; Ye, Changyun; Xu, Jianguo

    2016-12-07

    Escherichia coli is both of a widespread harmless gut commensal and a versatile pathogen of humans. Domestic animals are a well-known reservoir for pathogenic E. coli. However, studies of E. coli populations from wild animals that have been separated from human activities had been very limited. Here we obtained 580 isolates from intestinal contents of 116 wild Marmot Marmota himalayana from Qinghai-Tibet plateau, China, with five isolates per animal. We selected 125 (hereinafter referred to as strains) from the 580 isolates for genome sequencing, based on unique pulse field gel electrophoresis patterns and at least one isolate per animal. Whole genome sequence analysis revealed that all 125 strains carried at least one and the majority (79.2%) carried multiple virulence genes based on the analysis of 22 selected virulence genes. In particular, the majority of the strains carried virulence genes from different pathovars as potential 'hybrid pathogens'. The alleles of eight virulence genes from the Marmot E. coli were found to have diverged earlier than all known alleles from human and other animal E. coli. Phylogenetic analysis of the 125 Marmot E. coli genomes and 355 genomes selected from 1622 human and other E. coli strains identified two new phylogroups, G and H, both of which diverged earlier than the other phylogroups. Eight of the 12 well-known pathogenic E. coli lineages were found to share a most recent common ancestor with one or more Marmot E. coli strains. Our results suggested that the intestinal E. coli of the Marmots contained a diverse virulence gene pool and is potentially pathogenic to humans. These findings provided a new understanding of the evolutionary origin of pathogenic E. coli.

  4. Niche modeling predictions of the potential distribution of Marmota himalayana, the host animal of plague in Yushu County of Qinghai

    Directory of Open Access Journals (Sweden)

    Liang Lu

    2016-02-01

    Full Text Available Abstract Background After the earthquake on 14, April 2010 at Yushu in China, a plague epidemic hosted by Himalayan marmot (Marmota himalayana became a major public health concern during the reconstruction period. A rapid assessment of the distribution of Himalayan marmot in the area was urgent. The aims of this study were to analyze the relationship between environmental factors and the distribution of burrow systems of the marmot and to predict the distribution of marmots. Methods Two types of marmot burrows (hibernation and temporary in Yushu County were investigated from June to September in 2011. The location of every burrow was recorded with a global positioning system receiver. An ecological niche model was used to determine the relationship between the burrow occurrence data and environmental variables, such as land surface temperature (LST in winter and summer, normalized difference vegetation index (NDVI in winter and summer, elevation, and soil type. The predictive accuracies of the models were assessed by the area under the curve of the receiving operator curve. Results The models for hibernation and temporary burrows both performed well. The contribution orders of the variables were LST in winter and soil type, NDVI in winter and elevation for the hibernation burrow model, and LST in summer, NDVI in summer, soil type and elevation in the temporary burrow model. There were non-linear relationships between the probability of burrow presence and LST, NDVI and elevation. LST of 14 and 23 °C, NDVI of 0.22 and 0.60, and 4100 m were inflection points. A substantially higher probability of burrow presence was observed in swamp soil and dark felty soil than in other soil types. The potential area for hibernation burrows was 5696 km2 (37.7 % of Yushu County, and the area for temporary burrows was 7711 km2 (51.0 % of Yushu County. Conclusions The results suggested that marmots preferred warm areas with relatively low altitudes and good

  5. Activity of nucleic acid polymers in rodent models of HBV infection.

    Science.gov (United States)

    Schöneweis, Katrin; Motter, Neil; Roppert, Pia L; Lu, Mengji; Wang, Baoju; Roehl, Ingo; Glebe, Dieter; Yang, Dongliang; Morrey, John D; Roggendorf, Michael; Vaillant, Andrew

    2018-01-01

    Nucleic acid polymers (NAPs) block the release of HBsAg from infected hepatocytes. These compounds have been previously shown to have the unique ability to eliminate serum surface antigen in DHBV-infected Pekin ducks and achieve multilog reduction of HBsAg or HBsAg loss in patients with chronic HBV infection and HBV/HDV coinfection. In ducks and humans, the blockage of HBsAg release by NAPs occurs by the selective targeting of the assembly and/or secretion of subviral particles (SVPs). The clinically active NAP species REP 2055 and REP 2139 were investigated in other relevant animal models of HBV infection including woodchucks chronically infected with WHV, HBV transgenic mice and HBV infected SCID-Hu mice. The liver accumulation of REP 2139 in woodchucks following subcutaneous administration was examined and was found to be similar to that observed in mice and ducks. However, in woodchucks, NAP treatment was associated with only mild (36-79% relative to baseline) reductions in WHsAg (4/10 animals) after 3-5 weeks of treatment without changes in serum WHV DNA. In HBV infected SCID-Hu mice, REP 2055 treatment was not associated with any reduction of HBsAg, HBeAg or HBV DNA in the serum after 28 days of treatment. In HBV transgenic mice, no reductions in serum HBsAg were observed with REP 2139 with up to 12 weeks of treatment. In conclusion, the antiviral effects of NAPs in DHBV infected ducks and patients with chronic HBV infection were weak or absent in woodchuck and mouse models despite similar liver accumulation of NAPs in all these species, suggesting that the mechanisms of SVP assembly and or secretion present in rodent models differs from that in DHBV and chronic HBV infections. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  6. UTILIZAÇÃO DO CUSTEIO POR ABSORÇÃO PARA FINS GERENCIAIS

    OpenAIRE

    César Augusto Tibúrcio Silva

    2009-01-01

    O urso grizzly gasta o outono a caçar e comer marmotas (McGee, 294). Para tanto, ele move grandes e profundas pedras. Considerando em termos globais, este trabalho do urso, quando comparado com o seu tamanho e o da marmota, leva à conclusão de que o urso desperdiça tempo e energia. Como o inverno é geralmente longo e rigoroso, esta dedução pode ser precipitada. O urso talvez esteja praticando esporte, divertindo-se ou exercitando-se ou talvez variando sua dieta. Ou ainda tudo isto em conjun-t...

  7. An Archeological Overview and Management Plan for the U.S. Army Natick Research and Development Laboratories.

    Science.gov (United States)

    1984-06-01

    following mammal species: white-tailed deer, moose, bear, chipmunk, squirrel, raccoon, porcupine , woodchuck, gopher, skunk, hare, cotton-tail rabbit...fauna, such as mammoth, mastodon, giant beaver; all presently extinct. Biomass was low Ij in the tundra so there were no large herds of these mammals

  8. Control of Vertebrate Pests of Agricultural Crops.

    Science.gov (United States)

    Wingard, Robert G.; Studholme, Clinton R.

    This agriculture extension service publication of Pennsylvania State University discusses the damage from and control of vertebrate pests. Specific discussions describe the habits, habitat, and various control measures for blackbirds and crows, deer, meadow and pine mice, European starlings, and woodchucks. Where confusion with non-harmful species…

  9. Hepatitis virus protein X-Phenylalanine Hydroxylase fusion proteins identified in PKU mice treated with AAV-WPRE vectors

    Science.gov (United States)

    Utilizing the Pahenu2 mouse model for phenylketonuria (PKU), we developed an improved expression vector containing the Woodchuck Hepatitis Virus post-transcriptional regulatory element inserted into a rAAV-mPAH construct (rAAV-mPAH-WPRE) for treatment of PKU. Following portal vein delivery of these ...

  10. UTILIZAÇÃO DO CUSTEIO POR ABSORÇÃO PARA FINS GERENCIAIS

    Directory of Open Access Journals (Sweden)

    César Augusto Tibúrcio Silva

    2009-08-01

    Full Text Available O urso grizzly gasta o outono a caçar e comer marmotas (McGee, 294. Para tanto, ele move grandes e profundas pedras. Considerando em termos globais, este trabalho do urso, quando comparado com o seu tamanho e o da marmota, leva à conclusão de que o urso desperdiça tempo e energia. Como o inverno é geralmente longo e rigoroso, esta dedução pode ser precipitada. O urso talvez esteja praticando esporte, divertindo-se ou exercitando-se ou talvez variando sua dieta. Ou ainda tudo isto em conjun-to. Provavelmente, a energia obtida em decorrência da ingestão da marmota seja superior aos custos da caça. O presente texto revela como o custeio por absorção pode ser utilizado para fins gerenciais. Apresenta, inicialmente, discus-são acerca da não utilização do custeio por absorção com a referida finalidade, em razão de promover distorções nas decisões devido à arbitrariedade dos rateios e de incentivar a superprodu-ção, aspecto enfatizado pela bibliografia da área de contabilidade gerencial. Por fim, demonstra que tal sistema de custeio pode ser um meio de implantação de certas estratégias empresariais e um substituto para mensuração das denominadas externalidades. (Custeio por Absorção – Contabilidade Gerencial

  11. 50 CFR 32.38 - Maine.

    Science.gov (United States)

    2010-10-01

    ... wild turkey, coyote (see big game) fox, raccoon, woodchuck, squirrel, porcupine, skunk, snowshoe hare... all dogs the same day you release them (see § 26.21(b) of this chapter). C. Big Game Hunting. We allow... § 32.2(i)). D. Sport Fishing. [Reserved] Moosehorn National Wildlife Refuge A. Migratory Game Bird...

  12. 50 CFR 32.48 - New Hampshire.

    Science.gov (United States)

    2010-10-01

    ... launching areas outside the refuge. B. Upland Game Hunting. [Reserved] C. Big Game Hunting. We allow hunting.... We allow hunting of coyote (see C. Big Game Hunting), fox, raccoon, woodchuck, squirrel, porcupine... must pick up all dogs the same day you release them (see § 26.21(b) of this chapter). C. Big Game...

  13. Flood Control at Grafton, North Dakota, Park River.

    Science.gov (United States)

    1975-08-01

    expected to occur, in the escarpment forest include mice, shrews , voles, bats, rabbits, squirrels, muskrat, woodchuck, beaver, pocket gopher, ground...although short-grass prairie would probably eventually be invaded by either taller tame grasses, such as brome, or taller native grasses). 2. The ...grass prairie would eventually be invaded by either taller tame grasses (brome) or taller natives in this area. Thus, the statement that "there would

  14. Sex-specific determinants of fitness in a social mammal.

    Science.gov (United States)

    Lardy, Sophie; Allainé, Dominique; Bonenfant, Christophe; Cohas, Aurélie

    2015-11-01

    Sociality should evolve when the fitness benefits of group living outweigh the costs. Theoretical models predict an optimal group size maximizing individual fitness. However, beyond the number of individuals present in a group, the characteristics of these individuals, like their sex, are likely to affect the fitness payoffs of group living. Using 20 years of individually based data on a social mammal, the Alpine marmot (Marmota marmota), we tested for the occurrence of an optimal group size and composition, and for sex-specific effects of group characteristics on fitness. Based on lifetime data of 52 males and 39 females, our findings support the existence of an optimal group size maximizing male fitness and an optimal group composition maximizing fitness of males and females. Additionally, although group characteristics (i.e., size, composition and instability) affecting male and female fitness differed, fitness depended strongly on the number of same-sex subordinates within the social group in the two sexes. By comparing multiple measures of social group characteristics and of fitness in both sexes, we highlighted the sex-specific determinants of fitness in the two sexes and revealed the crucial role of intrasexual competition in shaping social group composition.

  15. Final Environmental Assessment for Republic of Singapore Air Force F-15SG Beddown at Mountain Home AFB

    Science.gov (United States)

    2007-03-01

    Bighorn Sheep, a BLM sensitive species. Two herds of California bighorn sheep occur in the area: the Owyhee River herd and the Bruneau/Jarbidge...Rivers herd . The Owyhee herd range includes portions of the East and South Forks of the Owyhee River, as well as Battle, Deep, and Dickshooter Creeks...Rabbit (Oryctolagus cuniculus) 12 12 North American Porcupine (Erethizon dorsatum) 1 1 Yellow-bellied Marmot (Marmota flaviventris) 1 1

  16. Early and adult social environments have independent effects on individual fitness in a social vertebrate.

    Science.gov (United States)

    Berger, Vérane; Lemaître, Jean-François; Allainé, Dominique; Gaillard, Jean-Michel; Cohas, Aurélie

    2015-08-22

    Evidence that the social environment at critical stages of life-history shapes individual trajectories is accumulating. Previous studies have identified either current or delayed effects of social environments on fitness components, but no study has yet analysed fitness consequences of social environments at different life stages simultaneously. To fill the gap, we use an extensive dataset collected during a 24-year intensive monitoring of a population of Alpine marmots (Marmota marmota), a long-lived social rodent. We test whether the number of helpers in early life and over the dominance tenure length has an impact on litter size at weaning, juvenile survival, longevity and lifetime reproductive success (LRS) of dominant females. Dominant females, who were born into a group containing many helpers and experiencing a high number of accumulated helpers over dominance tenure length showed an increased LRS through an increased longevity. We provide evidence that in a wild vertebrate, both early and adult social environments influence individual fitness, acting additionally and independently. These findings demonstrate that helpers have both short- and long-term effects on dominant female Alpine marmots and that the social environment at the time of birth can play a key role in shaping individual fitness in social vertebrates. © 2015 The Author(s).

  17. Animal models for HCV and HBV studies

    Directory of Open Access Journals (Sweden)

    Isabelle Chemin

    2007-02-01

    the infectivity of infectious clones of HCV without chimpanzees. Chimpanzees became infected when RNA transcripts from molecular clones were inoculated directly into the liver. The infection generated by such transfection did not differ significantly from that observed in animals infected intravenously with wild-type HCV. It furthermore permits true homologous challenge in studies of protective immunity and in testing the efficacy of vaccine candidates.

    Finally, this in vivo transfection system has made it possible to test for the first time the importance of genetic elements for HCV infectivity.

    Although chimpanzees are the only animals fully permissive for HBV infection, their use for research purpose is severely limited by the high costs and strong ethical constrains. The only alternative source of HBV-permissive hepatocytes is the Asian tree shrew Tupaia belangeri. Though experimental infection of these squirrel-like mammals, phylogenetically related to primates, results only in a mild, transient replication, primary hepatocytes isolated from T. belangeri turned out to be a reliable tool for in vitro HBV infection experiments.

    Along with invaluable infection studies in chimpanzees, avian and mammalian HBV-related viruses continue to offer ample opportunities for studies in naturally occurring hosts. In general, most of our progresses in hepatitis B virus research are based on infection studies with two HBV-related animal viruses: the woodchuck HBV (WHV, which infects the Eastern American woodchuck (Marmota monax, and the duck HBV (DHBV, which infects Peking ducks. Both animal models have been essential for understanding various steps of viral life-cycle and factors involved in establishment of virus

  18. Denaturing gradient gel electrophoresis analysis of fecal bacterial communities of marmot (Marmota marmota latirostris latirostris) in High Tatras (Slovakia) and their population fragmentation

    Czech Academy of Sciences Publication Activity Database

    Kopečný, Jan; Novotný, M.; Kmeť, V.

    2004-01-01

    Roč. 13, - (2004), s. 35-36 ISSN 1210-3209 Grant - others:Science and Technology Assistance Agency(SK) APVT-20-026102 Institutional research plan: CEZ:AV0Z5045916 Keywords : marmot * DGGE * Tatras Subject RIV: EE - Microbiology, Virology

  19. Hepatitis B virus nuclear export elements: RNA stem-loop α and β, key parts of the HBV post-transcriptional regulatory element.

    Science.gov (United States)

    Lim, Chun Shen; Brown, Chris M

    2016-09-01

    Many viruses contain RNA elements that modulate splicing and/or promote nuclear export of their RNAs. The RNAs of the major human pathogen, hepatitis B virus (HBV) contain a large (~600 bases) composite cis-acting 'post-transcriptional regulatory element' (PRE). This element promotes expression from these naturally intronless transcripts. Indeed, the related woodchuck hepadnavirus PRE (WPRE) is used to enhance expression in gene therapy and other expression vectors. These PRE are likely to act through a combination of mechanisms, including promotion of RNA nuclear export. Functional components of both the HBV PRE and WPRE are 2 conserved RNA cis-acting stem-loop (SL) structures, SLα and SLβ. They are within the coding regions of polymerase (P) gene, and both P and X genes, respectively. Based on previous studies using mutagenesis and/or nuclear magnetic resonance (NMR), here we propose 2 covariance models for SLα and SLβ. The model for the 30-nucleotide SLα contains a G-bulge and a CNGG(U) apical loop of which the first and the fourth loop residues form a CG pair and the fifth loop residue is bulged out, as observed in the NMR structure. The model for the 23-nucleotide SLβ contains a 7-base-pair stem and a 9-nucleotide loop. Comparison of the models with other RNA structural elements, as well as similarity searches of human transcriptome and viral genomes demonstrate that SLα and SLβ are specific to HBV transcripts. However, they are well conserved among the hepadnaviruses of non-human primates, the woodchuck and ground squirrel.

  20. Mutant woodchuck hepatitis virus genomes from virions resemble rearranged hepadnaviral integrants in hepatocellular carcinoma.

    OpenAIRE

    Kew, M C; Miller, R H; Chen, H S; Tennant, B C; Purcell, R H

    1993-01-01

    Although hepadnaviruses are implicated in the etiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence DR1, less often DR2, or in the cohesive overlap region. Integrants invariab...

  1. Comparative uptake of uranium, thorium, and plutonium by biota inhabiting a contaminated Tennessee floodplain

    International Nuclear Information System (INIS)

    Garten, C.T. Jr.; Bondietti, E.A.; Walker, R.L.

    1981-01-01

    The uptake of 238 U, 232 Th, and 239 Pu from soil by fescue, grasshoppers, and small mammals was compared at the contaminated White Oak Creek floodplain in East Tennessee. Comparisons of actinide uptake were based on analyses of radionuclide ratios (U/Pu and Th/Pu) in soil and biota. U:Pu ratios in small mammal carcasses (shrews, mice, and rats) and bone samples from larger mammals (rabbit, woodchuck, opossum, and raccoon) were significantly greater (P less than or equal to 0.05) than U/Pu ratios in soil (based on 8M HNO 3 extractable). There was no significant difference between Th/Pu ratios in animals and soil. The order of actinide accumulation by biota from the site relative to contaminated soil was U > Th approx. = Pu

  2. Suppression of guinea pig ileum induced contractility by plasma albumin of hibernators

    Science.gov (United States)

    Bruce, David S.; Ambler, Douglas L.; Henschel, Timothy M.; Oeltgen, Peter R.; Nilekani, Sita P.; Amstrup, Steven C.

    1992-01-01

    Previous studies suggest that hibernation may be regulated by internal opioids and that the putative “hibernation induction trigger” (HIT) may itself be an opioid. This study examined the effect of plasma albumin (known to bind HIT) on induced contractility of the guinea pig ileum muscle strip. Morphine (400 nM) depressed contractility and 100 nM naloxone restored it. Ten milligrams of lyophilized plasma albumin fractions from hibernating ground squirrels, woodchucks, black bears, and polar bears produced similar inhibition, with partial reversal by naloxone. Five hundredths mg of d-Ala2-d-Leu5-enkephalin (DADLE) also inhibited contractility and naloxone reversed it. Conclusions are that hibernating individuals of these species contain an HIT substance that is opioid in nature and summer animals do not; an endogenous opioid similar to leu-enkephalin may be the HIT compound or give rise to it.

  3. [Analysis on the results of etiology and serology of plague in Qinghai province from 2001 to 2010].

    Science.gov (United States)

    Yang, Yonghai; Wang, Mei; Zhao, Xiaolong; Zhao, Zhongzhi; Zhang, Aiping; Wei, Rongjie; Wei, Baiqing; Wang, Zuyun

    2014-02-01

    To analyze the results of etiology and serology of plague among human and infected animals in Qinghai province from 2001 to 2010. Thirty-seven cases of human infected with plague, 53 541 different animal samples, 5 685 sets of vector insects flea and 49 039 different animal serum samples were obtained between 2001 and 2010. A total of 7 811 samples of serum from healthy farmers and herdsmen in 14 counties in Qinghai from 2005 to 2007 were collected. Yersinia pestis (Y. pestis) were detected in visceral and secretions from human, infected animals and vector insects, respectively. Plague antigen was detected by reverse indirect hemagglutination assay (RIHA) in those samples. Indirect hemagglutination assay (IHA) was used to test plague FI antibody in serum of human and infected animals. 37 human plague cases were confirmed, 21 strains of plague Y. pestis were isolated from human cases and 14 positive were detected out. 133 of 7 811 samples of human serum were IHA positive, with the positive rate at 1.7%. A total of 146 strains of plague were isolated from infected animals and vector insects, 99 out of which were from infected animals, with a ratio of Marmota himalayan at 72.7% (72/99) and the other 47 were from vector insects, with a ratio of callopsylla solaris at 68.1% (32/47). The number of IHA and PIHA positive were 300 and 10, respectively. A total of 3 animals and 3 insects species were identified as new epidemic hosts for plague. The natural plague focus of Microtus fuscus was discovered and confirmed and coexisted with natural focus of Marmota himalayan in Chengduo county, Yushu prefecture. The epidemic situation of plague is distributed mainly in Haixi, Yushu and Hainan prefectures. From 2001 to 2010, animal infected with plague was detected in successive years and human plague was very common in Qinghai. New infected animals and vector insects species and new epidemic areas were confirmed, hence the trend of plague prevalence for humans and animals is very

  4. Use of nitrocellulose blotting for the study of hepatitis B surface antigen electrophoresed in agarose gels

    Energy Technology Data Exchange (ETDEWEB)

    McMichael, J C; Greisiger, L M; Millman, I [Institute for Cancer Research, Philadelphia, PA (USA). Fox Chase Cancer Center

    1981-08-28

    Nitrocellulose-protein blotting of serum electrophoresed in agarose gels has been adapted for the study of hepatitis B surface antigen (HBsAg). /sup 125/I-labeled anti-HBs was used as the antigen probe, and the electrophoretic migration was monitored by autoradiography. The method required 3 ..mu..l or less of serum and could detect as little as 1 pg of purified HBsAg. Typically, the authors observed two bands of HBsAg; a moving band which migrated about one-third the distance moved by human serum albumin and a non-migratory band which remained at the loading site. Some examples of the use of the method include: (1) empirical methods for correlating HBsAg concentration in serum to film darkness; (2) observations of mobility changes in serial sera from dialysis patients with chronic HBsAg antigenemia; and (3) detection of related antigens such as antigen from the PLC/PRF/5 hepatoma tissue culture line and the cross-reacting woodchuck hepatitis virus surface antigen (WHsAg).

  5. Comparison of fundamental and wideband harmonic contrast imaging of liver tumors.

    Science.gov (United States)

    Forsberg, F; Liu, J B; Chiou, H J; Rawool, N M; Parker, L; Goldberg, B B

    2000-03-01

    Wideband harmonic imaging (with phase inversion for improved tissue suppression) was compared to fundamental imaging in vivo. Four woodchucks with naturally occurring liver tumors were injected with Imagent (Alliance Pharmaceutical Corp., San Diego, CA). Randomized combinations of dose (0.05, 0.2 and 0.4 ml/kg) and acoustic output power (AO; 5, 25 and 63% or MI Siemens Medical Systems, Issaquah, WA). Tumor vascularity, conspicuity and contrast enhancement were rated by three independent observers. Imagent produced marked tumor enhancement and improved depiction of neovascularity at all dosages and AO settings in both modes. Tumor vascularity and enhancement correlated with mode, dose and AO (P < 0.002). Fundamental imaging produced more enhancement (P < 0.05), but tumor vascularity and conspicuity were best appreciated in harmonic mode (P < 0.05). Under the conditions studied here, the best approach was wideband harmonic imaging with 0.2 ml/kg of Imagent at an AO of 25%.

  6. Signs Observed Among Animal Species Infected with Raccoon Rabies Variant Virus, Massachusetts, USA, 1992–2010

    Directory of Open Access Journals (Sweden)

    Linda L. Han

    2011-11-01

    Full Text Available We analyzed signs occurring among domestic and wild terrestrial animal species infected with raccoon rabies variant virus (RRV in Massachusetts, 1992–2010. The clinical sign of aggression was significantly associated with rabid stray cats (odds ratio, OR = 2.3 and RRV affected major wild terrestrial animal species individually, which included raccoons (OR = 2.8, skunks (OR = 8.0, gray foxes (OR = 21.3, red foxes (OR = 10.4, woodchucks (OR = 4.7 and coyotes (OR = 27.6. While aggression is a useful predictor of rabies among wild animals, combinations of other signs such as ataxia, disorientation, and salivation are useful predictors of rabies among domestic animals. Pets reported with multiple clinical signs had significantly higher rabies positive testing result than those reported with single clinical sign (p < 0.001. The result suggested the importance of avoiding aggressive terrestrial wild animals and giving additional attention to pets with multiple clinical signs.

  7. [Origin of the plague microbe Yersinia pestis: structure of the process of speciation].

    Science.gov (United States)

    Suntsov, V V

    2012-01-01

    The origin and evolution of the plague microbe Yersinia pestis are considered in the context of propositions of modern Darwinism. It was shown that the plague pathogen diverged from the pseudotuberculous microbe Yersinia pseudotuberculosis O:1b in the mountain steppe landscapes of Central Asia in the Sartan: 22000-15000 years ago. Speciation occurred in the tarbagan (Marmota sibirica)--flea (Oropsylla silantiewi) parasitic system. The structure of the speciation process included six stages: isolation, genetic drift, enhancement of intrapopulational polymorphism, the beginning of pesticin synthesis (genetic conflict and emergence of hiatus), specialization (stabilization of characteristics), and adaptive irradiation (transformation of the monotypic species Y. pestis tarbagani into a polytypic species). The scenario opens up wide prospects for construction of the molecular phylogeny of the plague microbe Y. pestis and for investigation of the biochemical and molecular-genetic aspects of "Darwinian" evolution of pathogens from many other nature-focal infections.

  8. Assessment of ecological risk at the hydro pole warehousing yard located at Rimouski; Evaluation du risque ecologique que presente la cour d`entreposage de poteaux situee a Rimouski

    Energy Technology Data Exchange (ETDEWEB)

    Loranger, S.; Goudreau, R.; Courchesne, Y.; Langlet, B. [QSAR, Service d`analyse de risque, Montreal, PQ (Canada); Houde, L. [Hydro-Quebec, Montreal, PQ (Canada)

    1998-12-31

    Hydro-Quebec`s warehouse facility at Rimouski where hydro poles, treated with pentachlorophenol (PCP), are stored was chosen as the site for the application and validation of various approaches to evaluate ecological risk. The soil and ground water within the warehouse facility is contaminated with PCP as well as oil and grease beyond recommended limits. This site was chosen because of its proximity to the Rimouski River ( a salmon river), and the availability of data concerning the state of contamination in the region. A conceptual model was developed which describes the relationship between source, development, target and effect. Ingestion was the avenue of contaminant retention used to calculate exposure of the receptor organisms (Atlantic salmon, aquatic insects, red squirrels, the common woodchuck and the silver seagull). Toxicological reference values for the target area were taken from the literature where available, or calculated using a variety of recognized approaches. Organisms at risk are identified when the ratio of the exposure dosage and the reference value exceed 1 (one). Sensitivity and uncertainty analysis were carried out using a stochastic approach, aided by Monte Carlo simulations.

  9. Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

    Science.gov (United States)

    Becker, P S; Taylor, J A; Trobridge, G D; Zhao, X; Beard, B C; Chien, S; Adair, J; Kohn, D B; Wagner, J E; Shimamura, A; Kiem, H-P

    2010-10-01

    One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (Pgene-corrected cells in patients with FANCA.

  10. Older mothers follow conservative strategies under predator pressure: the adaptive role of maternal glucocorticoids in yellow-bellied marmots.

    Science.gov (United States)

    Monclús, Raquel; Tiulim, Justin; Blumstein, Daniel T

    2011-11-01

    When the maternal environment is a good predictor of the offspring environment, maternal glucocorticoid (GC) levels might serve to pre-program offspring to express certain phenotypes or life-history characteristics that will increase their fitness. We conducted a field study to assess the effects of naturally occurring maternal GC levels on their offspring in yellow-bellied marmots (Marmota flaviventris) subjected to different predator pressures. Maternal fecal corticosteroid metabolites (FCM) were positively correlated with predator pressure. Predators had both direct and indirect effects on pups. We found that older mothers with higher FCM levels had smaller and female-biased litters. Moreover, sons from older mothers with high FCM levels dispersed significantly more than those from older mothers with low FCM levels, whereas the opposite pattern was found in pups from younger mothers. These age-related effects may permit females to make adaptive decisions that increase their pups' fitness according to their current situation. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. [Macro- and microevolution as related to the problem of origin and global expansion of the plague pathogen Yersinia pestis].

    Science.gov (United States)

    Suntsov, V V; Suntsova, N I

    2008-01-01

    The ratio of macro- and microevolutionary processes is considered with reference to the ecological scenario of the origin of the plague pathogen and its subsequent natural and anthropogenic global expansion. The macroevolutionary transformation of the ancestral pseudotuberculosis microbe clone into the initial plague microbe Yersinia pestis tarbagani occurred in Central Asia at the end of the Late Pleistocene by a "vertical" Darwinian way in an inadaptive heterothermal continual intermediate environment--the Mongolian marmot Marmota sibirica-flea Oropsylla silantiewi system--via a sequence of unstable and currently extinct intermediate forms. Its natural geographic expansion on the "oil spot" principle in the postglacial time led to the microevolutionary formation of 20-30 hostal subspecies circulating in populations of the background species of burrowing rodents and pikas in arid areas of Eurasia. The intercontinental spread of the "marmot" and "rat" pathogen subspecies in the past few centuries has been exclusively anthropogenic, with the involvement of synanthropic (ship) rats.

  12. [The true story and advantages of the famous Hepatitis B virus core particles: Outlook 2016].

    Science.gov (United States)

    Pumpens, P; Grens, E

    2016-01-01

    This review article is a continuation of the paper "Hepatitis B core particles as a universal display model: a structure-function basis for development" written by Pumpens P. and Grens E., ordered by Professor Lev Kisselev and published in FEBS Letters, 1999, 442, 1-6. The past 17 years have strengthened the paper's finding that the human hepatitis B virus core protein, along with other Hepadnaviridae family member core proteins, is a mysterious, multifunctional protein. The core gene of the Hepadnaviridae genome encodes five partially collinear proteins. The most important of these is the HBV core protein p21, or HBc. It can self-assemble by forming viral HBc particles, but also plays a crucial role in the regulation of viral replication. Since 1986, the HBc protein has been one of the first and the most successful tools of the virus-like particle (VLP) technology. Later, the woodchuck hepatitis virus core protein (WHc) was also used as a VLP carrier. The Hepadnaviridae core proteins remain favourite VLP candidates for the knowledge-based design of future vaccines, gene therapy vectors, specifically targeted nanocontainers, and other modern nanotechnological tools for prospective medical use.

  13. Predators as prey at a Golden Eagle Aquila chrysaetos eyrie in Mongolia

    Science.gov (United States)

    Ellis, D.H.; Tsengeg, Pu; Whitlock, P.; Ellis, Merlin H.

    2000-01-01

    Although golden eagles (Aquila chrysaetos) have for decades been known to occasionally take large or dangerous quarry, the capturing of such was generally believed to be rare and/or the act of starved birds. This report provides details of an exceptional diet at a golden eagle eyrie in eastern Mongolia with unquantified notes on the occurrence of foxes at other eyries in Mongolia. Most of the prey we recorded were unusual, including 1 raven (Corvus corax), 3 demoiselle cranes (Anthropoides virgo), 1 upland buzzard (Buteo hemilasius), 3 owls, 27 foxes, and 11 Mongolian gazelles. Some numerical comparisons are of interest. Our value for gazelle calves (10 minimum count, 1997) represents 13% of 78 prey items and at least one adult was also present. Our total of only 15 hares (Lepus tolai) and 4 marmots (Marmota sibirica) compared to 27 foxes suggests not so much a preference for foxes, but rather that populations of more normal prey were probably depressed at this site. Unusual prey represented 65% of the diet at this eyrie.

  14. Replacement of the murine leukemia virus (MLV) envelope gene with a truncated HIV envelope gene in MLV generates a virus with impaired replication capacity

    International Nuclear Information System (INIS)

    Nack, Ursula; Schnierle, Barbara S.

    2003-01-01

    Murine leukemia virus (MLV) capsid particles can be efficiently pseudotyped with a variant of the HIV-1 envelope protein (Env) containing the surface glycoprotein gp120-SU and a carboxyl-terminally truncated transmembrane (TM) protein, with only seven cytoplasmic amino acids. MLV/HIV pseudotyped vector particles acquire the natural host tropism of HIV-1 and their entry is dependent on the presence of CD4 and an appropriate co-receptor on the surface of the target cell. We describe here the construction of chimeric MLV/HIV proviruses containing the truncated HIV envelope gene. The MLV/HIV provirus was generated by direct replacement of the MLV envelope gene with HIV Env coding sequences either with or without the additional inclusion of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). Chimeric MLV/HIV particles could be generated from transfected 293T cells and were able to infect CD4/CXCR4-positive target cells. However, the second round of infection of target cells was severely impaired, despite the fact that the WPRE element enhanced the amount of viral mRNA detected. Viral particles released from infected cells showed reduced HIV Env incorporation, indicating that additional factors required for efficient replication of MLV/HIV pseudotyped viruses are missing

  15. Small mammals of the Mongolian mountain steppe region near Erdensant: insights from live-trapping and bird pellet remains.

    Directory of Open Access Journals (Sweden)

    Joanne L. Isaac

    2005-12-01

    Full Text Available Relatively little is known of the distribution, abundance and ecology of small mammals in Mongolia and as a result there is scant knowledge of the effects of environmental and anthropogenic factors on small mammal populations. The aim of this study was to assess the occurrence of small mammals in mountain steppe habitat from live-trapping and analysis of mammal remains from raptor pellets and below nests. During live-trapping, root voles ( Microtus oeconemus were the most commonly caught species accounting for 47.5 % of captures, striped hamsters ( Cricetulus barabensis and pika ( Ochotona hyperborea accounted for 30 % and 22.5 % of captures respectively. Temperature influenced trapping success, with small mammals appearing to avoid being active at temperatures over 20 ̊C. The three species caught on the trapping grid appeared to avoid competition for resources through both temporal and spatial differences in the use of available habitat. Mammals identified from raptor pellets and other remains included the grey hamster ( Cricatulus migratorius , Siberian marmot ( Marmota sibirica , red fox ( Vulpes vulpes , long-tailed souslik ( Citellus undulatus and the Daurian mole ( Myospalax aspalax. Results are discussed in terms of their relevance to the conservation of mammals in Mongolia and their co-existence with livestock and humans.

  16. The Effect of Anthelmintic Treatment on Coccidia Oocyst Shedding in a Wild Mammal Host with Intermittent Cestode Infection

    Directory of Open Access Journals (Sweden)

    Radovan Václav

    2014-01-01

    Full Text Available While hosts are routinely exploited by a community of parasite species, the principles governing host responses towards parasites are unclear. Identifying the health outcomes of coinfections involving helminth macroparasites and microparasites is one area of importance for public and domestic animal health. For instance, it is controversial how deworming programmes affect incidence and severity of such important microparasite diseases as malaria. One problem is that most study systems involve domestic and laboratory animals with conditions hardly comparable to those of free-living animals. Here, we study the effect of anthelmintic treatment on coccidia infection intensity in wild Alpine marmots, M. marmota. Our results lend support to the hypothesis that helminth infection has a positive effect on concurrent microparasite infection. However, our work also points to the fact that within-host interactions between helminths and microparasites are context-dependent and can turn to negative ones once helminth burdens increase. Our study suggests that coccidia benefit from intermittent helminth infection in marmots due to the protective effects of helminth infection only during the early phase of the host’s active season. Also, the marmot’s response towards coccidia infection appears optimal only under no helminth infection when the host immune response towards coccidia would not be compromised, thereby pointing to the importance of regular intestinal helminth elimination by marmots just before hibernation.

  17. PET imaging of hepatocellular carcinoma with {sup 18}F-fluoroethylcholine and {sup 11}C-choline

    Energy Technology Data Exchange (ETDEWEB)

    Kolthammer, Jeffrey A.; Tenley, Nathan [Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH (United States); Corn, David J.; Wu, Chunying; Tian, Haibin; Wang, Yanming [University Hospitals Case Medical Center, Nuclear Medicine Division, Department of Radiology, Cleveland, OH (United States); Lee, Zhenghong [Case Western Reserve University, Department of Biomedical Engineering, Cleveland, OH (United States); University Hospitals Case Medical Center, Nuclear Medicine Division, Department of Radiology, Cleveland, OH (United States)

    2011-07-15

    Choline-based radiotracers have been studied for PET imaging of hepatocellular carcinoma (HCC). Using an {sup 18}F-labeled choline analog, instead of the {sup 11}C-labeled native choline, would facilitate its widespread use in the clinic. In this study, PET with {sup 18}F-fluoroethylcholine (FEC) and {sup 11}C-choline (CHOL) were compared using an animal model of HCC. The effects of fasting on the performance of choline-based tracers were also investigated. A woodchuck model of HCC was used to compare the two tracers, which were administered and imaged in sequence during the same imaging session. Dynamic PET images were generated spanning 50 min starting from tracer injection. Time-activity curves and tracer contrast were calculated in liver regions with tracer accumulation, and the contrast at a late time-point with the two tracers, and between fasted and nonfasted states, were compared. Foci of HCC with increased uptake ranged in size from 1.0 to 1.6 cm, with mean tumor-to-background contrast of 1.3 with FEC and 1.5 with CHOL at 50 min after injection. The tracers show similar patterns of uptake immediately following administration, and both activities plateaued at 10 min after injection. No significant differences in uptake dynamics or final contrast were observed between the fasted and nonfasted states. PET imaging of HCC is possible with both CHOL and FEC. Fasting was not found to affect accumulation of either tracer. These results encourage further investigation into the clinical utility of FEC for HCC imaging. (orig.)

  18. Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging.

    Science.gov (United States)

    Pocock, Ginger M; Zimdars, Laraine L; Yuan, Ming; Eliceiri, Kevin W; Ahlquist, Paul; Sherer, Nathan M

    2017-02-01

    Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include "burst" RNA nuclear export dynamics regulated by HIV-1's Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element-specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation. © 2017 Pocock et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  19. Mapping risk of plague in Qinghai-Tibetan Plateau, China.

    Science.gov (United States)

    Qian, Quan; Zhao, Jian; Fang, Liqun; Zhou, Hang; Zhang, Wenyi; Wei, Lan; Yang, Hong; Yin, Wenwu; Cao, Wuchun; Li, Qun

    2014-07-10

    Qinghai-Tibetan Plateau of China is known to be the plague endemic region where marmot (Marmota himalayana) is the primary host. Human plague cases are relatively low incidence but high mortality, which presents unique surveillance and public health challenges, because early detection through surveillance may not always be feasible and infrequent clinical cases may be misdiagnosed. Based on plague surveillance data and environmental variables, Maxent was applied to model the presence probability of plague host. 75% occurrence points were randomly selected for training model, and the rest 25% points were used for model test and validation. Maxent model performance was measured as test gain and test AUC. The optimal probability cut-off value was chosen by maximizing training sensitivity and specificity simultaneously. We used field surveillance data in an ecological niche modeling (ENM) framework to depict spatial distribution of natural foci of plague in Qinghai-Tibetan Plateau. Most human-inhabited areas at risk of exposure to enzootic plague are distributed in the east and south of the Plateau. Elevation, temperature of land surface and normalized difference vegetation index play a large part in determining the distribution of the enzootic plague. This study provided a more detailed view of spatial pattern of enzootic plague and human-inhabited areas at risk of plague. The maps could help public health authorities decide where to perform plague surveillance and take preventive measures in Qinghai-Tibetan Plateau.

  20. Prey preferences of the snow leopard (Panthera uncia: regional diet specificity holds global significance for conservation.

    Directory of Open Access Journals (Sweden)

    Salvador Lyngdoh

    Full Text Available The endangered snow leopard is a large felid that is distributed over 1.83 million km(2 globally. Throughout its range it relies on a limited number of prey species in some of the most inhospitable landscapes on the planet where high rates of human persecution exist for both predator and prey. We reviewed 14 published and 11 unpublished studies pertaining to snow leopard diet throughout its range. We calculated prey consumption in terms of frequency of occurrence and biomass consumed based on 1696 analysed scats from throughout the snow leopard's range. Prey biomass consumed was calculated based on the Ackerman's linear correction factor. We identified four distinct physiographic and snow leopard prey type zones, using cluster analysis that had unique prey assemblages and had key prey characteristics which supported snow leopard occurrence there. Levin's index showed the snow leopard had a specialized dietary niche breadth. The main prey of the snow leopard were Siberian ibex (Capra sibrica, blue sheep (Pseudois nayaur, Himalayan tahr (Hemitragus jemlahicus, argali (Ovis ammon and marmots (Marmota spp. The significantly preferred prey species of snow leopard weighed 55±5 kg, while the preferred prey weight range of snow leopard was 36-76 kg with a significant preference for Siberian ibex and blue sheep. Our meta-analysis identified critical dietary resources for snow leopards throughout their distribution and illustrates the importance of understanding regional variation in species ecology; particularly prey species that have global implications for conservation.

  1. Prey preferences of the snow leopard (Panthera uncia): regional diet specificity holds global significance for conservation.

    Science.gov (United States)

    Lyngdoh, Salvador; Shrotriya, Shivam; Goyal, Surendra P; Clements, Hayley; Hayward, Matthew W; Habib, Bilal

    2014-01-01

    The endangered snow leopard is a large felid that is distributed over 1.83 million km(2) globally. Throughout its range it relies on a limited number of prey species in some of the most inhospitable landscapes on the planet where high rates of human persecution exist for both predator and prey. We reviewed 14 published and 11 unpublished studies pertaining to snow leopard diet throughout its range. We calculated prey consumption in terms of frequency of occurrence and biomass consumed based on 1696 analysed scats from throughout the snow leopard's range. Prey biomass consumed was calculated based on the Ackerman's linear correction factor. We identified four distinct physiographic and snow leopard prey type zones, using cluster analysis that had unique prey assemblages and had key prey characteristics which supported snow leopard occurrence there. Levin's index showed the snow leopard had a specialized dietary niche breadth. The main prey of the snow leopard were Siberian ibex (Capra sibrica), blue sheep (Pseudois nayaur), Himalayan tahr (Hemitragus jemlahicus), argali (Ovis ammon) and marmots (Marmota spp). The significantly preferred prey species of snow leopard weighed 55±5 kg, while the preferred prey weight range of snow leopard was 36-76 kg with a significant preference for Siberian ibex and blue sheep. Our meta-analysis identified critical dietary resources for snow leopards throughout their distribution and illustrates the importance of understanding regional variation in species ecology; particularly prey species that have global implications for conservation.

  2. Strong social relationships are associated with decreased longevity in a facultatively social mammal.

    Science.gov (United States)

    Blumstein, Daniel T; Williams, Dana M; Lim, Alexandra N; Kroeger, Svenja; Martin, Julien G A

    2018-01-31

    Humans in strong social relationships are more likely to live longer because social relationships may buffer stressors and thus have protective effects. However, a shortcoming of human studies is that they often rely on self-reporting of these relationships. By contrast, observational studies of non-human animals permit detailed analyses of the specific nature of social relationships. Thus, discoveries that some social animals live longer and healthier lives if they are involved in social grooming, forage together or have more affiliative associates emphasizes the potential importance of social relationships on health and longevity. Previous studies have focused on the impact of social metrics on longevity in obligately social species. However, if sociality indeed has a key role in longevity, we might expect that affiliative relationships should also influence longevity in less social species. We focused on socially flexible yellow-bellied marmots ( Marmota flaviventer ) and asked whether female longevity covaries with the specific nature of social relationships. We quantified social relationships with social network statistics that were based on affiliative interactions, and then estimated the correlation between longevity and sociality using bivariate models. We found a significant negative phenotypic correlation between affiliative social relationship strength and longevity; marmots with greater degree, closeness and those with a greater negative average shortest path length died at younger ages. We conclude that sociality plays an important role in longevity, but how it does so may depend on whether a species is obligately or facultatively social. © 2018 The Author(s).

  3. Gene therapy with brain-derived neurotrophic factor as a protection: retinal ganglion cells in a rat glaucoma model.

    Science.gov (United States)

    Martin, Keith R G; Quigley, Harry A; Zack, Donald J; Levkovitch-Verbin, Hana; Kielczewski, Jennifer; Valenta, Danielle; Baumrind, Lisa; Pease, Mary Ellen; Klein, Ronald L; Hauswirth, William W

    2003-10-01

    To develop a modified adenoassociated viral (AAV) vector capable of efficient transfection of retinal ganglion cells (RGCs) and to test the hypothesis that use of this vector to express brain-derived neurotrophic factor (BDNF) could be protective in experimental glaucoma. Ninety-three rats received one unilateral, intravitreal injection of either normal saline (n = 30), AAV-BDNF-woodchuck hepatitis posttranscriptional regulatory element (WPRE; n = 30), or AAV-green fluorescent protein (GFP)-WPRE (n = 33). Two weeks later, experimental glaucoma was induced in the injected eye by laser application to the trabecular meshwork. Survival of RGCs was estimated by counting axons in optic nerve cross sections after 4 weeks of glaucoma. Transgene expression was assessed by immunohistochemistry, Western blot analysis, and direct visualization of GFP. The density of GFP-positive cells in retinal wholemounts was 1,828 +/- 299 cells/mm(2) (72,273 +/- 11,814 cells/retina). Exposure to elevated intraocular pressure was similar in all groups. Four weeks after initial laser treatment, axon loss was 52.3% +/- 27.1% in the saline-treated group (n = 25) and 52.3% +/- 24.2% in the AAV-GFP-WPRE group (n = 30), but only 32.3% +/- 23.0% in the AAV-BDNF-WPRE group (n = 27). Survival in AAV-BDNF-WPRE animals increased markedly and the difference was significant compared with those receiving either AAV-GFP-WPRE (P = 0.002, t-test) or saline (P = 0.006, t-test). Overexpression of the BDNF gene protects RGC as estimated by axon counts in a rat glaucoma model, further supporting the potential feasibility of neurotrophic therapy as a complement to the lowering of IOP in the treatment of glaucoma.

  4. Physiological and behavioral responses to the social environment

    International Nuclear Information System (INIS)

    Davis, D.E.

    1978-01-01

    Physiological and behavioral reactions to the social environment are mediated in nature principally through aggressive interactions, although in some cases other aspects of the environment such as temperature or predators are important. Observations from 1946-50 of changes in populations of rats after alteration of social conditions suggested the hypothesis that changes in birth and mortality rates followed aggressive interactions. The pituitary-adrenal-gonadal mechanism provided a process that could be tested in three types of conditions: laboratory, simulated field, and field. Changes in social environment can result from: seasonal changes in conditions; appearance of transients; habitat changes due to succession; and increase of population. It became apparent from laboratory research that a physiological feedback from aggressive behavior could reduce birth rates and increase mortality rates. Studies in nature showed that a reduction of Norway rat population by 38 percent was followed by a reduction of adrenal weight by 32 percent. Also as the population of rats increased the weight of the adrenals increased. A comprehensive study of woodchucks, started in 1957, showed that the alteration of age composition and the increase in immigration was associated with increased adrenal function. Research by others on lemmings shows that the adrenals at the peak of a population fluctuation are larger and produce more hormones than at the low point. No evidence was obtained to support the hypothesis that genetic selection for aggressive behavior within the population occurs during the increase or decline of a population. The changes occur within an individual. The future of studies of responses to the social environment will require experimental programs in nature that last for a decade or more, long enough to monitor changes in numbers under a variety of conditions

  5. Detection, Prevalence and Phylogenetic Relationships of Demodex spp and further Skin Prostigmata Mites (Acari, Arachnida) in Wild and Domestic Mammals.

    Science.gov (United States)

    Sastre, Natalia; Francino, Olga; Curti, Joseph N; Armenta, Tiffany C; Fraser, Devaughn L; Kelly, Rochelle M; Hunt, Erin; Silbermayr, Katja; Zewe, Christine; Sánchez, Armand; Ferrer, Lluís

    2016-01-01

    This study was conceived to detect skin mites in social mammals through real-time qPCR, and to estimate taxonomic Demodex and further Prostigmata mite relationships in different host species by comparing sequences from two genes: mitochondrial 16S rRNA and nuclear 18S rRNA. We determined the mite prevalence in the hair follicles of marmots (13%) and bats (17%). The high prevalence found in marmots and bats by sampling only one site on the body may indicate that mites are common inhabitants of their skin. Since we found three different mites (Neuchelacheles sp, Myobia sp and Penthaleus sp) in three bat species (Miotis yumanensis, Miotis californicus and Corynorhinus townsendii) and two different mites (both inferred to be members of the Prostigmata order) in one marmot species (Marmota flaviventris), we tentatively concluded that these skin mites 1) cannot be assigned to the same genus based only on a common host, and 2) seem to evolve according to the specific habitat and/or specific hair and sebaceous gland of the mammalian host. Moreover, two M. yumanensis bats harbored identical Neuchelacheles mites, indicating the possibility of interspecific cross-infection within a colony. However, some skin mites species are less restricted by host species than previously thought. Specifically, Demodex canis seems to be more transmissible across species than other skin mites. D. canis have been found mostly in dogs but also in cats and captive bats. In addition, we report the first case of D. canis infestation in a domestic ferret (Mustela putorius). All these mammalian hosts are related to human activities, and D. canis evolution may be a consequence of this relationship. The monophyletic Demodex clade showing closely related dog and human Demodex sequences also supports this likely hypothesis.

  6. Detection, Prevalence and Phylogenetic Relationships of Demodex spp and further Skin Prostigmata Mites (Acari, Arachnida in Wild and Domestic Mammals.

    Directory of Open Access Journals (Sweden)

    Natalia Sastre

    Full Text Available This study was conceived to detect skin mites in social mammals through real-time qPCR, and to estimate taxonomic Demodex and further Prostigmata mite relationships in different host species by comparing sequences from two genes: mitochondrial 16S rRNA and nuclear 18S rRNA. We determined the mite prevalence in the hair follicles of marmots (13% and bats (17%. The high prevalence found in marmots and bats by sampling only one site on the body may indicate that mites are common inhabitants of their skin. Since we found three different mites (Neuchelacheles sp, Myobia sp and Penthaleus sp in three bat species (Miotis yumanensis, Miotis californicus and Corynorhinus townsendii and two different mites (both inferred to be members of the Prostigmata order in one marmot species (Marmota flaviventris, we tentatively concluded that these skin mites 1 cannot be assigned to the same genus based only on a common host, and 2 seem to evolve according to the specific habitat and/or specific hair and sebaceous gland of the mammalian host. Moreover, two M. yumanensis bats harbored identical Neuchelacheles mites, indicating the possibility of interspecific cross-infection within a colony. However, some skin mites species are less restricted by host species than previously thought. Specifically, Demodex canis seems to be more transmissible across species than other skin mites. D. canis have been found mostly in dogs but also in cats and captive bats. In addition, we report the first case of D. canis infestation in a domestic ferret (Mustela putorius. All these mammalian hosts are related to human activities, and D. canis evolution may be a consequence of this relationship. The monophyletic Demodex clade showing closely related dog and human Demodex sequences also supports this likely hypothesis.

  7. DNA immunization with fusion of CTLA-4 to hepatitis B virus (HBV core protein enhanced Th2 type responses and cleared HBV with an accelerated kinetic.

    Directory of Open Access Journals (Sweden)

    Ying Yin

    Full Text Available BACKGROUND: Typically, DNA immunization via the intramuscular route induces specific, Th1-dominant immune responses. However, plasmids expressing viral proteins fused to cytotoxic T lymphocyte antigen 4 (CTLA-4 primed Th2-biased responses and were able to induced effective protection against viral challenge in the woodchuck model. Thus, we addressed the question in the mouse model how the Th1/Th2 bias of primed immune responses by a DNA vaccine influences hepatitis B virus (HBV clearance. PRINCIPAL FINDINGS: Plasmids expressing HBV core protein (HBcAg or HBV e antigen and HBcAg fused to the extracellular domain of CTLA-4 (pCTLA-4-HBc, CD27, and full length CD40L were constructed. Immunizations of these DNA plasmids induced HBcAg-specific antibody and cytotoxic T-cell responses in mice, but with different characteristics regarding the titers and subtypes of specific antibodies and intensity of T-cell responses. The plasmid pHBc expressing HBcAg induced an IgG2a-dominant response while immunizations of pCTLA-4-HBc induced a balanced IgG1/IgG2a response. To assess the protective values of the immune responses of different characteristics, mice were pre-immunized with pCTLA-4-HBc and pHBc, and challenged by hydrodynamic injection (HI of pAAV/HBV1.2. HBV surface antigen (HBsAg and DNA in peripheral blood and HBcAg in liver tissue were cleared with significantly accelerated kinetics in both groups. The clearance of HBsAg was completed within 16 days in immunized mice while more than 50% of the control mice are still positive for HBsAg on day 22. Stronger HBcAg-specific T-cell responses were primed by pHBc correlating with a more rapid decline of HBcAg expression in liver tissue, while anti-HBs antibody response developed rapidly in the mice immunized with pCTLA-4-HBc, indicating that the Th1/Th2 bias of vaccine-primed immune responses influences the mode of viral clearance. CONCLUSION: Viral clearance could be efficiently achieved by Th1/Th2-balanced

  8. Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001, a programmed cell death protein-1 (PD-1) monoclonal antibody.

    Science.gov (United States)

    Fu, Jie; Wang, Fang; Dong, Li-Hou; Zhang, Jing; Deng, Cheng-Lian; Wang, Xue-Li; Xie, Xin-Yao; Zhang, Jing; Deng, Ruo-Xian; Zhang, Li-Bo; Wu, Hai; Feng, Hui; Chen, Bo; Song, Hai-Feng

    2017-05-01

    JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC 50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC 50 of 3.0 and 3.1 nmol/L, respectively. Furthermore, JS-001 displayed distinct species cross-reactivity: it could bind to the PD-1 antigen on the peripheral blood mononuclear cells (PBMCs) of humans and cynomolgus monkeys, but not to those of mice and woodchucks; the K d values for the interaction between JS-001 and PD-1 antigens on CD8 + T cells of human and cynomolgus monkey were 2.1 nmol/L and 1.2 nmol/L, respectively. In vitro, treatment with JS-001 (0.01-10 μg/mL) dose-dependently stimulated human T cell proliferation, as well as IFN-γ and TNF-α secretion. In HBsAg-vaccinated cynomolgus monkeys, the expression of PD-1 + /CD4 + and PD-1 + /CD8 + was significantly elevated, intramuscular injection of JS-001 (1 and 10 mg/kg) resulted in dramatic decreases in PD-1 + /CD4 + and PD-1 + /CD8 + expression in a dose-dependent manner, which was supported by PD-1 receptor occupancy (RO) results. In the PK study, 18 cynomolgus monkeys treated with single, ascending doses of 1, 10, and 75 mg/kg, and another 6 cynomolgus monkeys received 10 mg/kg successive administration. The plasma clearance of JS-001 followed a linear PK profile with single administration in the 1 and 10 mg/kg groups and a non-linear PK profile in the 75 mg/kg group. In the successive 10 mg/kg administration group, no drug accumulation was observed. But the AUC from the last exposure was lower than that of the first

  9. Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism.

    Science.gov (United States)

    Niu, Congrong; Li, Li; Daffis, Stephane; Lucifora, Julie; Bonnin, Marc; Maadadi, Sarah; Salas, Eduardo; Chu, Ruth; Ramos, Hilario; Livingston, Christine M; Beran, Rudolf K; Garg, Abhishek V; Balsitis, Scott; Durantel, David; Zoulim, Fabien; Delaney, William E; Fletcher, Simon P

    2018-05-01

    GS-9620, an oral agonist of toll-like receptor 7 (TLR7), is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the woodchuck and chimpanzee models of CHB. Herein, we investigated the molecular mechanisms that contribute to the antiviral response to GS-9620 using in vitro models of hepatitis B virus (HBV) infection. Cryopreserved primary human hepatocytes (PHH) and differentiated HepaRG (dHepaRG) cells were infected with HBV and treated with GS-9620, conditioned media from human peripheral blood mononuclear cells treated with GS-9620 (GS-9620 conditioned media [GS-9620-CM]), or other innate immune stimuli. The antiviral and transcriptional response to these agents was determined. GS-9620 had no antiviral activity in HBV-infected PHH, consistent with low level TLR7 mRNA expression in human hepatocytes. In contrast, GS-9620-CM induced prolonged reduction of HBV DNA, RNA, and antigen levels in PHH and dHepaRG cells via a type I interferon (IFN)-dependent mechanism. GS-9620-CM did not reduce covalently closed circular DNA (cccDNA) levels in either cell type. Transcriptional profiling demonstrated that GS-9620-CM strongly induced various HBV restriction factors - although not APOBEC3A or the Smc5/6 complex - and indicated that established HBV infection does not modulate innate immune sensing or signaling in cryopreserved PHH. GS-9620-CM also induced expression of immunoproteasome subunits and enhanced presentation of an immunodominant viral peptide in HBV-infected PHH. Type I IFN induced by GS-9620 durably suppressed HBV in human hepatocytes without reducing cccDNA levels. Moreover, HBV antigen presentation was enhanced, suggesting additional components of the TLR7-induced immune response played a role in the antiviral response to GS-9620 in animal models of CHB. GS-9620 is a drug currently being tested in clinical trials for the treatment of chronic

  10. The influence of sulfur and hair growth on stable isotope diet estimates for grizzly bears.

    Directory of Open Access Journals (Sweden)

    Garth Mowat

    Full Text Available Stable isotope ratios of grizzly bear (Ursus arctos guard hair collected from bears on the lower Stikine River, British Columbia (BC were analyzed to: 1 test whether measuring δ34S values improved the precision of the salmon (Oncorhynchus spp. diet fraction estimate relative to δ15N as is conventionally done, 2 investigate whether measuring δ34S values improves the separation of diet contributions of moose (Alces alces, marmot (Marmota caligata, and mountain goat (Oreamnos americanus and, 3 examine the relationship between collection date and length of hair and stable isotope values. Variation in isotope signatures among hair samples from the same bear and year were not trivial. The addition of δ34S values to mixing models used to estimate diet fractions generated small improvement in the precision of salmon and terrestrial prey diet fractions. Although the δ34S value for salmon is precise and appears general among species and areas, sulfur ratios were strongly correlated with nitrogen ratios and therefore added little new information to the mixing model regarding the consumption of salmon. Mean δ34S values for the three terrestrial herbivores of interest were similar and imprecise, so these data also added little new information to the mixing model. The addition of sulfur data did confirm that at least some bears in this system ate marmots during summer and fall. We show that there are bears with short hair that assimilate >20% salmon in their diet and bears with longer hair that eat no salmon living within a few kilometers of one another in a coastal ecosystem. Grizzly bears are thought to re-grow hair between June and October however our analysis of sectioned hair suggested at least some hairs begin growing in July or August, not June and, that hair of wild bears may grow faster than observed in captive bears. Our hair samples may have been from the year of sampling or the previous year because samples were collected in summer when

  11. The influence of sulfur and hair growth on stable isotope diet estimates for grizzly bears.

    Science.gov (United States)

    Mowat, Garth; Curtis, P Jeff; Lafferty, Diana J R

    2017-01-01

    Stable isotope ratios of grizzly bear (Ursus arctos) guard hair collected from bears on the lower Stikine River, British Columbia (BC) were analyzed to: 1) test whether measuring δ34S values improved the precision of the salmon (Oncorhynchus spp.) diet fraction estimate relative to δ15N as is conventionally done, 2) investigate whether measuring δ34S values improves the separation of diet contributions of moose (Alces alces), marmot (Marmota caligata), and mountain goat (Oreamnos americanus) and, 3) examine the relationship between collection date and length of hair and stable isotope values. Variation in isotope signatures among hair samples from the same bear and year were not trivial. The addition of δ34S values to mixing models used to estimate diet fractions generated small improvement in the precision of salmon and terrestrial prey diet fractions. Although the δ34S value for salmon is precise and appears general among species and areas, sulfur ratios were strongly correlated with nitrogen ratios and therefore added little new information to the mixing model regarding the consumption of salmon. Mean δ34S values for the three terrestrial herbivores of interest were similar and imprecise, so these data also added little new information to the mixing model. The addition of sulfur data did confirm that at least some bears in this system ate marmots during summer and fall. We show that there are bears with short hair that assimilate >20% salmon in their diet and bears with longer hair that eat no salmon living within a few kilometers of one another in a coastal ecosystem. Grizzly bears are thought to re-grow hair between June and October however our analysis of sectioned hair suggested at least some hairs begin growing in July or August, not June and, that hair of wild bears may grow faster than observed in captive bears. Our hair samples may have been from the year of sampling or the previous year because samples were collected in summer when bears were

  12. Para um Programa de Estudo do Neolítico em Portugal

    Directory of Open Access Journals (Sweden)

    Victor dos Santos GONÇALVES

    2009-10-01

    Full Text Available RESUMEN: El autor presenta, en líneas generales, los principales problemas de análisis del Neolítico en Portugal. Problemas que sólo en algunos casos son exclusivos del territorio portugués, ya que la mayor parte de ellos están ligados a la compleja evolución global del Neolítico en el Mediterráneo occidental. A continuación va a referirse a las propias dificultades intrínsecas para la definición de un concepto de Neolítico, e indica la escasez de información que todavía hoy existe a propósito del Neolítico portugués. Cita como ejemplo de las distorsiones provocadas por esta situación el caso de la cerámica cardial, escasa en el Neolítico antiguo portugués, donde abunda la cerámica incisa e impresa no cardial. En lo que se refiere al Neolítico antiguo, señala las principales estaciones encontradas hasta hoy en Portugal y alude más ampliamente a propósito de una, inédita el abrigo «das Bocas» (Rio Maior. A continuación, analiza las perspectivas con que se tendrá que abordar el fenómeno megalítico, planteando diversos problemas y enumerando las posibles acepciones para la palabra. Igualmente se refiere a la relación entre las inhumaciones en tres grutas localizadas en la región de Alcanena (la «Gruta dos Carrascos», la «Lapa da Galinha» y la «Gruta da Marmota» y una de las fases del megalitismo coincidente con el Neolítico medio. Sin embargo, como subraya el autor, únicamente un trabajo pluridisciplinar y de equipo podrá contribuir para obtener soluciones positivas a este problema.ABSTRACT: The Author presents an outline of the mam problems of the analysis of the Neolithic in Portugal. Problems that only in certain cases are exclusively found in Portuguese territory, since most of them are connected with the global evolution of the Neolithic in the Western Mediterranean. He refers the difficulties to found a definition for the concept of Neolithic and he points out the shortage of information that still

  13. El yacimiento de Lezetxiki (Gipuzkoa, País Vasco. Los niveles musterienses.

    Directory of Open Access Journals (Sweden)

    Amelia Baldeón

    1993-01-01

    pantera. El nivel III conoce oscilaciones climáticas que reflejan la sedimentología y los pólenes, presencia de fauna fría -rinoceronte lanudo, reno, marmota- y más templada -castor, ciervo, bisonte-. Hay restos de hogares y restos humanos atribuidos al hombre de Neanderthal. La industria no presenta ningún paralelismo con las facies clásicas y todos los datos apuntan a que bien los procesos tafonómicos o la complejidad en la identificación del depósito debido a los buzamientos cruzados del relleno (N-S y W-E impiden más precisiones. En este nivel se da un claro predominio del equipamiento musteriense -a nivel técnico y tipológico- con importante presencia de materiales netamente auriñacienses. Cierran la secuencia un nivel Gravetiense (el II y otro Magdaleniense Final (el I.

  14. Hepatitis B virus DNA integration and transactivation of cellular genes

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2007-02-01

    Full Text Available

    Chronic hepatitis B virus (HBV infection is etiologically related to human hepatocellular carcinoma (HCC. Most HCCs contain integrated HBV DNA in hepatocyte, suggesting that the integration may be involved in carcinogenesis. Available data on the integrants from human hepatocellular carcinomas seem to represent primary integrants as well as the products of secondary rearrangements. By means of structural analyses of the possible primary integrants, it has been observed that the replication intermediates of the viral genome are the preferred substrates for integration. The integrated HBV DNA and the target cellular DNA are invariably associated with deletions, possibly reflecting the substrate for, and the mechanism of, the integration reaction. The host DNA sequences as well as the target site of integration in chromosomes are selected randomly suggesting that HBV DNA integration should bring about random mutagenic effects. Analysis of the samples recovered from hepatocellular carcinomas show that the integrated HBV DNA can mediate secondary rearrangements of chromosomes, such as translocations, inversions, deletions and (possibly amplifications. The integration of HBV DNA into the host genome occurs at early steps of clonal tumor expansion. The integration has been shown in a number of cases to affect a variety of cancer-related genes and to exert insertional mutagenesis. However, in contrast to the woodchuck model, in which specific HBV-DNA integration is detectable in most cases, insertional activation or inactivation of cellular genes appears to be a rare event in man. The discovery of transactivating functions exerted by HBx and truncated HBs(urface proteins supports the notion that these could be relevant to hepatocarcinogenesis as these transactivator sequences have been found in a large number of HCC tumors or hepatoma-derived cell lines. The HBx