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Sample records for ferrets

  1. Ferret nutrition.

    PubMed

    Johnson-Delaney, Cathy A

    2014-09-01

    The domestic ferret (Mustela putorious furo) is a strict carnivore, also referred to as an obligate carnivore. Its dentition and gastrointestinal tract are adapted to a carnivorous diet. Its ancestor, the European polecat (Mustela putorius), feeds on birds and other small vertebrates. Domesticated ferrets have been fed mink feeds, cat foods, and now mostly subsist on commercial ferret diets formulated specifically to meet their needs.

  2. Mycoplasmosis in Ferrets

    PubMed Central

    Desjardins, Danielle R.; Lim, Ailam; Bolin, Carole; Johnson-Delaney, Cathy A.; Resau, James H.; Garner, Michael M.; Bolin, Steven R.

    2012-01-01

    We report an outbreak of severe respiratory disease associated with a novel Mycoplasma species in ferrets. During 2009–2012, a respiratory disease characterized by nonproductive coughing affected ≈8,000 ferrets, 6–8 weeks of age, which had been imported from a breeding facility in Canada. Almost 95% became ill, but almost none died. Treatments temporarily decreased all clinical signs except cough. Postmortem examinations of euthanized ferrets revealed bronchointerstitial pneumonia with prominent hyperplasia of bronchiole-associated lymphoid tissue. Immunohistochemical analysis with polyclonal antibody against Mycoplasma bovis demonstrated intense staining along the bronchiolar brush border. Bronchoalveolar lavage samples from 12 affected ferrets yielded fast-growing, glucose-fermenting mycoplasmas. Nucleic acid sequence analysis of PCR-derived amplicons from portions of the 16S rDNA and RNA polymerase B genes failed to identify the mycoplasmas but showed that they were most similar to M. molare and M. lagogenitalium. These findings indicate a causal association between the novel Mycoplasma species and the newly recognized pulmonary disease. PMID:23092744

  3. Immunity to influenza in ferrets

    PubMed Central

    McLaren, C.; Potter, C. W.; Jennings, R.

    1974-01-01

    The degree of immunity due to cross-reactions between antibody to influenza virus A/Hong Kong/1/68 and A/England/42/72 was studied in ferrets. Ferrets were immunized with the viruses by either live infection or by inoculation with inactivated virus vaccines. The vaccines were given with Freund's incomplete adjuvant or were given to ferrets previously infected with influenza virus A/PR/8/34. As a result of these immunizations the animals all produced similar titres of serum HI antibody to the immunizing virus, although the degree of cross-reaction with the other virus strain was variable. After immunization the animals were challenged by infection with an A/Eng/42/72-like virus and their degree of immunity was measured. It was found that the greatest immunity was in ferrets previously infected with the homologous A/Eng/42/72 virus. Animals previously infected with A/HK/68 virus also showed a measurable degree of immunity to A/Eng/42/72 infection, and this was greater than that found in animals given inactivated virus vaccines. The immunity produced by the vaccines was approximately equal, regardless of which vaccine or method of immunization was used. Thus, live infection produced a more effective, broader immunity than did the use of inactivated virus vaccines. PMID:4531448

  4. Information on black-footed ferret biology collected within the framework of ferret conservation

    USGS Publications Warehouse

    Biggins, Dean E.

    2012-01-01

    Once feared to be extinct, black-footed ferrets (Mustela nigripes) were rediscovered near Meeteetse, Wyoming, in 1981, resulting in renewed conservation and research efforts for this highly endangered species. A need for information directly useful to recovery has motivated much monitoring of ferrets since that time, but field activities have enabled collection of data relevant to broader biological themes. This special feature is placed in a context of similar books and proceedings devoted to ferret biology and conservation. Articles include general observations on ferrets, modeling of potential impacts of ferrets on prairie dogs (Cynomys spp.), discussions on relationships of ferrets to prairie dog habitats at several spatial scales (from individual burrows to patches of burrow systems) and a general treatise on the status of black-footed ferret recovery.

  5. Systemic Coronaviral Disease in 5 Ferrets

    PubMed Central

    Autieri, Christopher R; Miller, Cassandra L; Scott, Kathleen E; Kilgore, Alexandra; Papscoe, Victoria A; Garner, Michael M; Haupt, Jennifer L; Bakthavatchalu, Vasudevan; Muthupalani, Sureshkumar; Fox, James G

    2015-01-01

    The prevalence of reported systemic coronaviral disease in ferrets (Mustela putorius furo), which resembles the dry form of feline infectious peritonitis, has been increasing in the literature since its initial diagnosis and characterization approximately 10 y ago. Here we describe the clinical signs, pathologic findings, and diagnosis by immunohistochemistry using an FIPV3-70 monoclonal antibody of systemic coronaviral disease in 5 ferrets, 2 of which were strictly laboratory-housed; the remaining 3 were referred from veterinary private practices. This case report illustrates the importance of considering FRSCV infection as a differential diagnosis in young, debilitated ferrets with abdominal masses and other supporting clinical signs. PMID:26678368

  6. Systemic Coronaviral Disease in 5 Ferrets.

    PubMed

    Autieri, Christopher R; Miller, Cassandra L; Scott, Kathleen E; Kilgore, Alexandra; Papscoe, Victoria A; Garner, Michael M; Haupt, Jennifer L; Bakthavatchalu, Vasudevan; Muthupalani, Sureshkumar; Fox, James G

    2015-12-01

    The prevalence of reported systemic coronaviral disease in ferrets (Mustela putorius furo), which resembles the dry form of feline infectious peritonitis, has been increasing in the literature since its initial diagnosis and characterization approximately 10 y ago. Here we describe the clinical signs, pathologic findings, and diagnosis by immunohistochemistry using an FIPV3-70 monoclonal antibody of systemic coronaviral disease in 5 ferrets, 2 of which were strictly laboratory-housed; the remaining 3 were referred from veterinary private practices. This case report illustrates the importance of considering FRSCV infection as a differential diagnosis in young, debilitated ferrets with abdominal masses and other supporting clinical signs. PMID:26678368

  7. Ultrasonographic visualization of the adrenal glands of healthy ferrets and ferrets with hyperadrenocorticism.

    PubMed

    Kuijten, Andrea Maria; Schoemaker, Nico J; Voorhout, George

    2007-01-01

    A protocol was developed to compare the ultrasonographic characteristics of the adrenal glands of 21 healthy ferrets and 37 ferrets with hyperadrenocorticism. By using specific landmarks, the adrenal glands were imaged in 97% of the cases. The adrenal glands of ferrets with hyperadrenocorticism had a significantly increased thickness, with changes in shape, structure, and echogenicity compared to the adrenal glands of healthy ferrets. Based on the findings of the study, adrenal glands may be classified as abnormal when they have a rounded appearance, increased size of the cranial/caudal pole (thickness >3.9 mm), a heterogeneous structure, increased echogenicity, and/or signs of mineralization.

  8. Get More from Your Data with PyFerret

    NASA Astrophysics Data System (ADS)

    Burger, E. F.; Smith, K. M.; Manke, A. B.; Hankin, S.; O'Brien, K.

    2015-12-01

    Ferret is an interactive scientific visualization and analysis environment designed to meet the needs of oceanographers and meteorologists analyzing large and complex gridded data sets. PyFerret is a Python module, as well as a stand-alone program, that extends all the Ferret functionality for Python programmers. For users of traditional Ferret, PyFerret can be used as a backward-compatible, "drop-in" replacement for traditional Ferret, but with improved visualization tools, more powerful data analysis, and easier generation of user-defined functions. For Python users, PyFerret permits convenient, powerful, and efficient analyses of large datasets, whether local or remote. Combining Python with Ferret multiplies the strengths of each environment, so that one can more easily access, analyze, and visualize self-describing data.

  9. Comparison of the blood coagulation profiles of ferrets and rats.

    PubMed

    Takahashi, Saya; Hirai, Norihiko; Shirai, Mitsuyuki; Ito, Katsuaki; Asai, Fumitoshi

    2011-07-01

    The aim of this study was to examine the blood coagulation profiles of ferrets and compare them with those of rats. The ferret activated partial thromboplastin time (aPTT) was slightly longer than the rat aPTT. In contrast, the ferret prothrombin time and thrombin time were profoundly shorter than the corresponding rat values. The fibrinogen level in ferret plasma was 2 times higher than that in rats. Heparin prolonged all blood coagulation times in a concentration-dependent manner in both ferret and rat plasma. A significantly (P<0.01) higher concentration of heparin was required to double the aPTT in ferrets than rats. These blood coagulation data for ferrets will be useful in experimental animal studies.

  10. Echocardiographic diagnosis of dirofilariasis in a ferret.

    PubMed

    Sasai, H; Kato, K; Sasaki, T; Koyama, S; Kotani, T; Fukata, T

    2000-04-01

    Heartworm disease is described in a 14-month-old neutered female ferret (Mustela putorius furo) which had a three-week history of sneezing, anorexia and dyspnoea. Echocardiography revealed the presence of heartworms as hyperechoic densities within the right atrial and ventricular cavities. At necropsy, four Dirofilaria immitis parasites (three females, one male) were found in the right heart, the cranial vena cava and the caudal vena cava. Histopathological findings were similar to those reported in canine heartworm disease. Echocardiography may be a useful method of diagnosis of heartworm disease in the ferret. PMID:10812548

  11. Rabies in Ferret Badgers, Southeastern China

    PubMed Central

    Zhang, Shoufeng; Tang, Qing; Wu, Xianfu; Liu, Ye; Zhang, Fei; Rupprecht, Charles E.

    2009-01-01

    Ferret badger–associated human rabies cases emerged in China in 1994. We used a retrospective epidemiologic survey, virus isolation, laboratory diagnosis, and nucleotide sequencing to document its reemergence in 2002–2008. Whether the cause is spillover from infected dogs or recent host shift and new reservoir establishment requires further investigation. PMID:19523299

  12. Activity in the ferret: oestradiol effects and circadian rhythms

    NASA Technical Reports Server (NTRS)

    Stockman, E. R.; Albers, H. E.; Baum, M. J.; Wurtman, R. J. (Principal Investigator)

    1985-01-01

    The present study was conducted to determine whether oestradiol increases activity in the European ferret (Mustela furo), whether this effect is sexually dimorphic, and whether a 24-h rhythm is present in the ferret's daily activity. The activity of male and female adult, postpubertally gonadectomized ferrets was monitored while they were maintained singly on a 13:11 light-dark cycle, before and after implantation with oestradiol-17 beta. Gonadectomized male and female ferrets exhibited equal levels of activity, and neither sex exhibited a significant change in activity following oestradiol implantation. None of the ferrets exhibited a strong circadian rhythm, although weak 24-h rhythms and shorter harmonic rhythms were present. Golden hamsters (Mesocricetus auratus), monitored in an identical manner, exhibited strong circadian rhythms. It was concluded that oestradiol administration may not cause an increase in activity in the ferret, and that this species lacks a strong circadian activity rhythm.

  13. First survey of endoparasites in pet ferrets in Italy.

    PubMed

    d'Ovidio, D; Pepe, P; Ianniello, D; Noviello, E; Quinton, Jean-Francois; Cringoli, G; Rinaldi, L

    2014-06-16

    Endoparasites are infrequently reported in ferrets. A cross-sectional survey was conducted to determine the prevalence of intestinal parasites in pet ferrets in southern Italy. Fresh fecal samples were randomly collected from 50 ferrets housed in pet shops or privately owned. All fecal samples were processed using the FLOTAC pellet technique to identify and count helminthic eggs/larvae and protozoan cysts/oocysts. In addition, the samples were analyzed also by the Remel XpectGiardia/Cryptosporidium immunoassay. Intestinal parasites were detected in 15 out of 50 ferrets (30%). Eggs of ancylostomids were found in 28.0% (14/50) of the animals and oocysts of Sarcocystis were detected in one ferret (2.0%). None of the samples was positive for Cryptosporidium or Giardia. To the authors' knowledge, this is the first report of sarcosporidiosis in a pet ferret in Italy.

  14. Flexible Gastrointestinal Endoscopy in Ferrets (Mustela putorius furo).

    PubMed

    Pignon, Charly; Huynh, Minh; Husnik, Roman; Jekl, Vladimir

    2015-09-01

    Gastrointestinal disease is a common complaint in ferrets (Mustela putorius furo). Their relatively simple and short gastrointestinal tract makes them good candidates for flexible endoscopy. However, apart from a few references in biomedical research articles, there is little information on the use of flexible endoscopy in ferrets. This review describes patient preparation, equipment, and select gastrointestinal endoscopy techniques in ferrets, including esophagoscopy, gastroscopy, duodenoscopy, percutaneous endoscopic gastrostomy, jejunoileoscopy, colonoscopy, and biopsy.

  15. Black-footed ferret digging activity in summer

    USGS Publications Warehouse

    Eads, David A.; Biggins, Dean E.; Marsh, Dustin; Millspaugh, Joshua J.; Livieri, Travis M.

    2012-01-01

    Black-footed ferrets (Mustela nigripes) excavate soil from prairie dog (Cynomys spp.) burrows, thereby creating characteristic soil deposits at burrow openings. These soil deposits have been observed only rarely in summer. We monitored adult ferrets during June–October of the years 2007 and 2008 on a 452-ha colony of black-tailed prairie dogs (Cynomys ludovicianus) in the Conata Basin, South Dakota. We located and identified ferret excavations during nighttime spotlight surveys for ferrets and daytime sampling of prairie dog burrow openings around locations where ferrets were located via spotlight. We accumulated 48 observations of in-process or recently completed ferret excavations during spotlight surveys (21 in 2007, 27 in 2008) and located 51 diggings during daytime burrow sampling (25 in 2007, 26 in 2008). We located diggings during 5.5% of spotlight observations, most frequently in July–August. These results collectively suggest ferrets may frequently excavate soil in summer, because prairie dogs frequently use soil to plug burrow openings and tunnels in defense against ferrets. Prairie dogs might frequently destroy soil deposits left by ferrets during summer, thereby reducing detection of diggings by biologists.

  16. Reintroduction of the black-footed ferret (Mustela nigripes)

    USGS Publications Warehouse

    Miller, B.; Biggins, D.; Hanebury, L.; Vargas, A.

    1994-01-01

    The black-footed ferret (Mustela nigripes) (Figure 27.1) is a small, secretive, nocturnal member of the family Mustelidae (Hall, 1981; Honacki, Kurman and Koeppl, 1982). Ferrets have an obligate dependence on the prairie dog (Cynomys spp.) community, utilizing the prairie dog for food and its burrows for shelter (Campbell et al., 1987).

  17. Responses of Siberian ferrets to secondary zinc phosphide poisoning

    USGS Publications Warehouse

    Hill, E.F.; Carpenter, J.W.

    1982-01-01

    The hazard of operational-type applications of zinc phosphide (Zn3P2) on a species closely related to the black-footed ferret (Mustela nigripes), was evaluated by feeding 16 Siberian ferrets (M. eversmanni) rats that had been killed by consumption of 2% zinc phosphide treated bait or by an oral dose of 40, 80, or 160 mg of Zn3P2. All ferrets accepted rats and a single emesis by each of 3 ferrets was the only evidence of acute intoxication. All ferrets learned to avoid eating gastrointestinal tracts of the rats. Subacute zinc phosphide toxicity in the ferrets was indicated by significant decreases (18-48%) in hemoglobin, increases of 35-91 % in serum iron, and elevated levels of serum globulin, cholesterol, and triglycerides. Hemoglobin/iron, urea nitrogen/creatinine, and albumin/globulin ratios also were altered by the treatments. This study demonstrated that Siberian ferrets, or other species with a sensitive emetic reflex, are afforded a degree of protection from acute zinc phosphide poisoning due to its emetic action. The importance of toxicity associated with possible respiratory, liver, and kidney damage indicated by altered blood chemistries is not known.

  18. Clinical Profiles Associated with Influenza Disease in the Ferret Model

    PubMed Central

    Stark, Gregory V.; Long, James P.; Ortiz, Diana I.; Gainey, Melicia; Carper, Benjamin A.; Feng, Jingyu; Miller, Stephen M.; Bigger, John E.; Vela, Eric M.

    2013-01-01

    Influenza A viruses continue to pose a threat to human health; thus, various vaccines and prophylaxis continue to be developed. Testing of these products requires various animal models including mice, guinea pigs, and ferrets. However, because ferrets are naturally susceptible to infection with human influenza viruses and because the disease state resembles that of human influenza, these animals have been widely used as a model to study influenza virus pathogenesis. In this report, a statistical analysis was performed to evaluate data involving 269 ferrets infected with seasonal influenza, swine influenza, and highly pathogenic avian influenza (HPAI) from 16 different studies over a five year period. The aim of the analyses was to better qualify the ferret model by identifying relationships among important animal model parameters (endpoints) and variables of interest, which include survival, time-to-death, changes in body temperature and weight, and nasal wash samples containing virus, in addition to significant changes from baseline in selected hematology and clinical chemistry parameters. The results demonstrate that a disease clinical profile, consisting of various changes in the biological parameters tested, is associated with various influenza A infections in ferrets. Additionally, the analysis yielded correlates of protection associated with HPAI disease in ferrets. In all, the results from this study further validate the use of the ferret as a model to study influenza A pathology and to evaluate product efficacy. PMID:23472182

  19. Cloned ferrets produced by somatic cell nuclear transfer

    PubMed Central

    Li, Ziyi; Sun, Xingshen; Chen, Juan; Liu, Xiaoming; Wisely, Samantha M.; Zhou, Qi; Renard, Jean-Paul; Leno, Gregory H.; Engelhardt, John F.

    2007-01-01

    Somatic cell nuclear transfer (SCNT) offers great potential for developing better animal models of human disease. The domestic ferret (Mustela putorius furo) is an ideal animal model for influenza infections and potentially other human respiratory diseases such as cystic fibrosis, where mouse models have failed to reproduce the human disease phenotype. Here, we report the successful production of live cloned, reproductively competent, ferrets using species-specific SCNT methodologies. Critical to developing a successful SCNT protocol for the ferret was the finding that hormonal treatment, normally used for superovulation, adversely affected the developmental potential of recipient oocytes. The onset of Oct4 expression was delayed and incomplete in parthenogenetically activated oocytes collected from hormone-treated females relative to oocytes collected from females naturally mated with vasectomized males. Stimulation induced by mating and in vitro oocyte maturation produced the optimal oocyte recipient for SCNT. Although nuclear injection and cell fusion produced mid-term fetuses at equivalent rates (~3–4%), only cell fusion gave rise to healthy surviving clones. Single cell fusion rates and the efficiency of SCNT were also enhanced by placing two somatic cells into the perivitelline space. These species-specific modifications facilitated the birth of live, healthy, and fertile cloned ferrets. The development of microsatellite genotyping for domestic ferrets confirmed that ferret clones were genetically derived from their respective somatic cells and unrelated to their surrogate mother. With this technology, it is now feasible to begin generating genetically defined ferrets for studying transmissible and inherited human lung diseases. Cloning of the domestic ferret may also aid in recovery and conservation of the endangered black-footed ferret and European mink. PMID:16584722

  20. Transponders as permanent identification markers for domestic ferrets, black-footed ferrets, and other wildlife

    USGS Publications Warehouse

    Fagerstone, Kathleen A.; Johns, Brad E.

    1987-01-01

    A 0.05-g transponder implanted subcutaneously was tested to see if it provided a reliable identification method. In laboratory tests 20 domestic ferrets (Mustela putorius furo) received transponders and were monitored for a minimum of 6 months. None showed signs of inflammation, and necropsies conducted at the end of the study showed no scar tissue or transponder migration. Seven of 23 transponders failed during the test because of leakage through the plastic case, and a glass case is now being manufactured that does not have the leakage problem. During mark-recapture studies in September and October 1985, transponders were implanted in 20 black-footed ferrets (M. nigripes), 11 of which were subsequently recaptured and 9 of which were brought into captivity; none showed signs of inflammation. Transponders provide a reliable new method for identifying hard-to-mark wildlife with a unique, permanent number than can be read with the animal in-hand or by remote equipment.

  1. A technique for evaluating black-footed ferret habitat

    USGS Publications Warehouse

    Biggins, Dean E.; Miller, Brian J.; Hanebury, Louis R.; Oakleaf, Bob; Farmer, Adrian H.; Crete, Ron; Dood, Arnold

    1993-01-01

    In this paper, we provide a model and step-by-step procedures for rating a prairie dog (Cynomys sp.) complex for the reintroduction of black-footed ferrets (Mustela nigripes). An important factor in the model is an estimate of the number of black-footed ferret families a prairie dog complex can support for a year; thus, the procedures prescribe how to estimate the size of a prairie dog complex and the density of prairie dogs. Other attributes of the model are qualitative: arrangement of colonies, potential for plague and canine distemper, potential for prairie dog expansion, abundance of predators, future resource conflicts and ownership stability, and public and landowner attitudes about prairie dogs and black-footed ferrets. Because of the qualitative attributes in the model, a team approach is recommended for ranking complexes of prairie dogs for black-footed ferret reintroduction.

  2. Interface between black-footed ferret research and operational conservation

    USGS Publications Warehouse

    Biggins, Dean E.; Livieri, Travis M.; Breck, Stewart W.

    2011-01-01

    Questions and problems that emerged during operational conservation of black-footed ferrets (Mustela nigripes) have been addressed by a wide variety of studies. Early results from such studies often were communicated orally during meetings of recovery groups and in written form using memoranda, unpublished reports, and theses. Typically, implementation of results preceded their publication in widely distributed journals. Many of these studies eventually were published in journals, and we briefly summarize the contents of 8 volumes and special features of journals that have been dedicated to the biology of ferrets and issues in ferret recovery. This year marks the 30th anniversary of rediscovery of the black-footed ferret, and the 7 papers of the following Special Feature summarize data collected over nearly that span of time.

  3. Immunoprophylaxis of respiratory syncytial virus infection in the infant ferret.

    PubMed

    Suffin, S C; Prince, G A; Muck, K B; Porter, D D

    1979-07-01

    Infant ferrets can be protected from respiratory syncytical virus challenge at 3 days of age by gestational infection of their mothers. Ferrets acquire their immunity to respiratory syncytial virus postpartum via immunizing products of lactation. The level of protection against viral replication correlates with the maternal serum neutralizing titer or a concomitant factor. Passive administration of adult ferret serum with a neutralizing titer of 1:1024 or greater, either i.p. or orally does not confer immunity. A nonantibody-mediated protective mechanism appears to play an important role in protecting the infant ferret from respiratory syncytial virus replication. Our findings allow the testing of the efficacy of future human vaccines before human clinical trial. PMID:448139

  4. The black-footed ferret: on the brink of recovery?

    PubMed

    Santymire, Rachel M; Livieri, Travis M; Branvold-Faber, Heather; Marinari, Paul E

    2014-01-01

    In an attempt to save the species from extinction, the last remaining 18 black-footed ferrets (Mustela nigripes) were trapped up from the wild to initiate a captive breeding program. Nearly 30 years later more than 8,000 black-footed ferrets have been produced in captivity and approximately 4,100 animals have been reintroduced into 20 sites in eight US states (Arizona, New Mexico, Utah, Colorado, Kansas, Wyoming, South Dakota and Montana), Mexico and Canada. However, full recovery of the species has yet to be achieved, mainly due to limited viable habitat, disease and reduced fecundity. This chapter will highlight the advances in the black-footed ferret recovery program over the last 10 years including: (1) adaptive management techniques employed for the captive population; (2) development of new reintroduction sites and associated challenges facing wild black-footed ferrets; and (3) optimization of assisted reproductive techniques to secure the future of this rare species. PMID:25091909

  5. Fecal bile acids of black-footed ferrets

    USGS Publications Warehouse

    Richardson, Louise; Johnson, M.K.; Clark, T.W.; Schroder, M.H.

    1986-01-01

    Fecal bile acid characteristics have been used to identify scats to species of origin. Fecal bile acids in scats from 20 known black-footed ferrets ( Mustela nigripes ), 7 other known small carnivores, and 72 of unknown origin were analyzed to determine if this procedure could be used as a tool to verify ferret presence in an area. Seventeen ferret scats were suitable for analysis and had a mean fecal bile acid index of 156 ± 9. This was significantly different from mean indices for the other carnivores; however, substantial overlap among confidence intervals occurred for badgers, kit foxes, and especially long-tailed weasels. We conclude this method is not useful for making positive identifications if individual ferret scats and suggest that we may be able to definitively identify individual scats with reasonable confidence by using gas-liquid chromatography.

  6. Characterization of antibodies against ferret immunoglobulins, cytokines and CD markers.

    PubMed

    Martel, Cyril Jean-Marie; Aasted, Bent

    2009-12-15

    Ferret IgG and IgM were purified from normal serum, while ferret IgA was purified from bile. The estimated molecular weights of the immunoglobulin gamma, alpha and mu heavy chains were found to be 54kDa, 69kDa and 83kDa, respectively. For immunological (ELISA) quantification of ferret immunoglobulins, we identified and characterized polyclonal antibodies towards ferret IgG, IgM and IgA. We also identified 22 monoclonal antibodies (mAbs) raised mostly against human CD markers which cross-reacted with ferret leukocytes. These antibodies were originally specific against human CD8, CD9, CD14, CD18, CD25, CD29, CD32, CD44, CD61, CD71, CD79b, CD88, CD104, CD172a and mink CD3. Finally, we identified 4 cross-reacting mAbs with specificities against ferret interferon-gamma, TNF-alpha, interleukin-4 and interleukin-8.

  7. Establishment of serological test to detect antibody against ferret coronavirus

    PubMed Central

    MINAMI, Shohei; TERADA, Yutaka; SHIMODA, Hiroshi; TAKIZAWA, Masaki; ONUMA, Mamoru; OTA, Akihiko; OTA, Yuichi; AKABANE, Yoshihito; TAMUKAI, Kenichi; WATANABE, Keiichiro; NAGANUMA, Yumiko; KANAGAWA, Eiichi; NAKAMURA, Kaneichi; OHASHI, Masanari; TAKAMI, Yoshinori; MIWA, Yasutsugu; TANOUE, Tomoaki; OHWAKI, Masao; OHTA, Jouji; UNE, Yumi; MAEDA, Ken

    2016-01-01

    Since there is no available serological methods to detect antibodies to ferret coronavirus (FRCoV), an enzyme-linked immunosorbent assay (ELISA) using recombinant partial nucleocapsid (N) proteins of the ferret coronavirus (FRCoV) Yamaguchi-1 strain was developed to establish a serological method for detection of FRCoV infection. Many serum samples collected from ferrets recognized both a.a. 1–179 and a.a. 180–374 of the N protein, but two serum samples did not a.a. 180–374 of the N protein. This different reactivity was also confirmed by immunoblot analysis using the serum from the ferret.Therefore, the a.a. 1–179 of the N protein was used as an ELISA antigen. Serological test was carried out using sera or plasma of ferrets in Japan. Surprisingly, 89% ferrets in Japan had been infected with FRCoV. These results indicated that our established ELISA using a.a. 1–179 of the N protein is useful for detection of antibody to FRCoV for diagnosis and seroepidemiology of FRCoV infection. PMID:26935842

  8. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease.

    PubMed

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J; Tyler, Scott R; Tisoncik-Go, Jennifer; Brawand, David; Law, G Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J; Kelly, Sara M; Chang, Jean; Thomas, Matthew J; Johnson, Jeremy; Berlin, Aaron M; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M; Tumpey, Terrence M; Siepel, Adam; Wisely, Samantha M; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F; Palermo, Robert E; Katze, Michael G

    2014-12-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the 'gold standard' for modeling human influenza virus infection and transmission. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotated 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterized the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time-course data and showed distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis disease progression, we showed that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with cystic fibrosis disease.

  9. Tetralogy of Fallot in a 6-year-old albino ferret (Mustela putorius furo)

    PubMed Central

    Laniesse, Delphine; Hébert, Julie; Larrat, Sylvain; Hélie, Pierre; Pouleur-Larrat, Bénédicte; Belanger, Marie C.

    2014-01-01

    Tetralogy of Fallot associated with bidirectional shunting across a large ventricular septal defect, was found in a 6-year-old ferret. The prognosis associated with tetralogy of Fallot is usually poor. This case is interesting given the advanced age of the ferret. The bidirectional shunting, responsible for an acyanotic disease, may explain the unexpected prolonged survival in this ferret. PMID:24790231

  10. Feral ferrets (Mustela furo) as hosts and sentinels of tuberculosis in New Zealand

    PubMed Central

    Byrom, AE; Caley, P; Paterson, BM; Nugent, G

    2015-01-01

    Abstract The control and eventual eradication of bovine tuberculosis (TB) poses major challenges in New Zealand, given the variety of wildlife species susceptible to TB, many of which are capable of onwards transmission of Mycobacterium bovis infection. Here we discuss the role of feral ferrets (Mustela furo), focussing on potential transmission or risk pathways that have implications for management of TB. Firstly inter-specific transmission to ferrets. Ferrets scavenge potentially infected wildlife, including other ferrets, thus prevalence of TB can be amplified through ferrets feeding on tuberculous carcasses, particularly brushtail possums (Trichosurus vulpecula). Secondly intra-specific transmission between ferrets. The rate of ferret-ferret transmission depends on population density, and in some places ferret densities exceed the estimated threshold for disease persistence. TB can therefore potentially be maintained independently of other sources of infection. Thirdly transmission from ferrets to other wildlife. These include the main wildlife maintenance host, brushtail possums, that will occasionally scavenge potentially tuberculous ferret carcasses. Fourthly transmission from ferrets to livestock. This is considered to occur occasionally, but the actual rate of transmission has never been measured. Fifthly geographical spread. M. bovis-infected ferrets can travel large distances and cause new outbreaks of TB at locations previously free of TB, which may have caused an expansion of TB-endemic areas.Ferrets play a complex role in the TB cycle in New Zealand; they are capable of contracting, amplifying and transmitting M. bovis infection, sometimes resulting in ferret populations with a high prevalence of TB. However, ferret population densities are usually too low to sustain infection independently, and transmission to other wildlife or livestock appears a rarer event than with possums. Nevertheless, management of ferrets remains a key part of the National

  11. Feral ferrets (Mustela furo) as hosts and sentinels of tuberculosis in New Zealand.

    PubMed

    Byrom, A E; Caley, P; Paterson, B M; Nugent, G

    2015-06-01

    The control and eventual eradication of bovine tuberculosis (TB) poses major challenges in New Zealand, given the variety of wildlife species susceptible to TB, many of which are capable of onwards transmission of Mycobacterium bovis infection. Here we discuss the role of feral ferrets (Mustela furo), focussing on potential transmission or risk pathways that have implications for management of TB. Firstly inter-specific transmission to ferrets. Ferrets scavenge potentially infected wildlife, including other ferrets, thus prevalence of TB can be amplified through ferrets feeding on tuberculous carcasses, particularly brushtail possums (Trichosurus vulpecula). Secondly intra-specific transmission between ferrets. The rate of ferret-ferret transmission depends on population density, and in some places ferret densities exceed the estimated threshold for disease persistence. TB can therefore potentially be maintained independently of other sources of infection. Thirdly transmission from ferrets to other wildlife. These include the main wildlife maintenance host, brushtail possums, that will occasionally scavenge potentially tuberculous ferret carcasses. Fourthly transmission from ferrets to livestock. This is considered to occur occasionally, but the actual rate of transmission has never been measured. Fifthly geographical spread. M. bovis-infected ferrets can travel large distances and cause new outbreaks of TB at locations previously free of TB, which may have caused an expansion of TB-endemic areas. Ferrets play a complex role in the TB cycle in New Zealand; they are capable of contracting, amplifying and transmitting M. bovis infection, sometimes resulting in ferret populations with a high prevalence of TB. However, ferret population densities are usually too low to sustain infection independently, and transmission to other wildlife or livestock appears a rarer event than with possums. Nevertheless, management of ferrets remains a key part of the National Pest

  12. Importance of lunar and temporal conditions for spotlight surveys of adult black-footed ferrets

    USGS Publications Warehouse

    Eads, David A.; Jachowski, David S.; Millspaugh, Joshua J.; Biggins, Dean E.

    2012-01-01

    Black-footed ferrets (Mustela nigripes) spend most daylight hours underground in prairie dog (Cynomys) burrows and exhibit aboveground movements primarily at night. Moonlight can influence the activity patterns of ferrets and, consequently, might influence the efficiency of spotlight surveys used by biologists to monitor ferret populations. We related detection of adult ferrets during postbreeding spotlight surveys to lunar and temporal conditions. We most frequently located ferrets during surveys in which the moon breached the horizon. The data suggested intersexual differences in response to moonlight. We located male ferrets most frequently during nights with greater moon illumination, but we did not detect a correlation between moon illumination and spotlight detection of female ferrets. In general, moonlight could facilitate aboveground navigation by ferrets. However, it seems activity under bright moonlight could be costly for female ferrets while they raise young. Detection of ferrets also varied among months. We detected female ferrets most frequently in August–September, when mothers increase hunting efforts to acquire prey for growing offspring (kits). Detection of adult female ferrets declined in October, when kits were likely independent of their mother. We located male ferrets most frequently in September–October, when males might increase activity to monitor female ferrets and male competitors. Consideration of lunar and temporal influences and standardization of postbreeding surveys could enhance site-specific assessment of reintroduction success and across-site assessment of species recoveiy progress. We suggest that postbreeding surveys for ferrets should be enhanced by concentrating efforts in August–September during moonlit nights when the moon is above the horizon.

  13. Hemagglutinin Stalk Immunity Reduces Influenza Virus Replication and Transmission in Ferrets.

    PubMed

    Nachbagauer, Raffael; Miller, Matthew S; Hai, Rong; Ryder, Alex B; Rose, John K; Palese, Peter; García-Sastre, Adolfo; Krammer, Florian; Albrecht, Randy A

    2015-12-30

    We assessed whether influenza virus hemagglutinin stalk-based immunity protects ferrets against aerosol-transmitted H1N1 influenza virus infection. Immunization of ferrets by a universal influenza virus vaccine strategy based on viral vectors expressing chimeric hemagglutinin constructs induced stalk-specific antibody responses. Stalk-immunized ferrets were cohoused with H1N1-infected ferrets under conditions that permitted virus transmission. Hemagglutinin stalk-immunized ferrets had lower viral titers and delayed or no virus replication at all following natural exposure to influenza virus.

  14. Flowpath evaluation and reconnaissance by remote field Eddy current testing (FERRET)

    SciTech Connect

    Smoak, A.E.; Zollinger, W.T.

    1993-12-31

    This document describes the design and development of FERRET (Flowpath Evaluation and Reconnaisance by Remote-field Eddy current Testing). FERRET is a system for inspecting the steel pipes which carry cooling water to underground nuclear waste storage tanks. The FERRET system has been tested in a small scale cooling pipe mock-up, an improved full scale mock-up, and in flaw detection experiments. Early prototype designs of FERRET and the FERRET launcher (a device which inserts, moves, and retrieves probes from a piping system) as well as the field-ready design are discussed.

  15. Hemagglutinin Stalk Immunity Reduces Influenza Virus Replication and Transmission in Ferrets.

    PubMed

    Nachbagauer, Raffael; Miller, Matthew S; Hai, Rong; Ryder, Alex B; Rose, John K; Palese, Peter; García-Sastre, Adolfo; Krammer, Florian; Albrecht, Randy A

    2016-03-01

    We assessed whether influenza virus hemagglutinin stalk-based immunity protects ferrets against aerosol-transmitted H1N1 influenza virus infection. Immunization of ferrets by a universal influenza virus vaccine strategy based on viral vectors expressing chimeric hemagglutinin constructs induced stalk-specific antibody responses. Stalk-immunized ferrets were cohoused with H1N1-infected ferrets under conditions that permitted virus transmission. Hemagglutinin stalk-immunized ferrets had lower viral titers and delayed or no virus replication at all following natural exposure to influenza virus. PMID:26719251

  16. Hemagglutinin Stalk Immunity Reduces Influenza Virus Replication and Transmission in Ferrets

    PubMed Central

    Nachbagauer, Raffael; Miller, Matthew S.; Hai, Rong; Ryder, Alex B.; Rose, John K.; Palese, Peter; García-Sastre, Adolfo

    2015-01-01

    We assessed whether influenza virus hemagglutinin stalk-based immunity protects ferrets against aerosol-transmitted H1N1 influenza virus infection. Immunization of ferrets by a universal influenza virus vaccine strategy based on viral vectors expressing chimeric hemagglutinin constructs induced stalk-specific antibody responses. Stalk-immunized ferrets were cohoused with H1N1-infected ferrets under conditions that permitted virus transmission. Hemagglutinin stalk-immunized ferrets had lower viral titers and delayed or no virus replication at all following natural exposure to influenza virus. PMID:26719251

  17. Bioelectric Characterization of Epithelia from Neonatal CFTR Knockout Ferrets

    PubMed Central

    Fisher, John T.; Tyler, Scott R.; Zhang, Yulong; Lee, Ben J.; Liu, Xiaoming; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Luo, Meihui; Xie, Weiliang; Yi, Yaling; Zhou, Weihong; Song, Yi; Keiser, Nicholas; Wang, Kai; de Jonge, Hugo R.

    2013-01-01

    Cystic fibrosis (CF) is a life-shortening, recessive, multiorgan genetic disorder caused by the loss of CF transmembrane conductance regulator (CFTR) chloride channel function found in many types of epithelia. Animal models that recapitulate the human disease phenotype are critical to understanding pathophysiology in CF and developing therapies. CFTR knockout ferrets manifest many of the phenotypes observed in the human disease, including lung infections, pancreatic disease and diabetes, liver disease, malnutrition, and meconium ileus. In the present study, we have characterized abnormalities in the bioelectric properties of the trachea, stomach, intestine, and gallbladder of newborn CF ferrets. Short-circuit current (ISC) analysis of CF and wild-type (WT) tracheas revealed the following similarities and differences: (1) amiloride-sensitive sodium currents were similar between genotypes; (2) responses to 4,4′-diisothiocyano-2,2′-stilbene disulphonic acid were 3.3-fold greater in CF animals, suggesting elevated baseline chloride transport through non-CFTR channels in a subset of CF animals; and (3) a lack of 3-isobutyl-1-methylxanthine (IBMX)/forskolin–stimulated and N-(2-Naphthalenyl)-((3,5-dibromo-2,4-dihydroxyphenyl)methylene)glycine hydrazide (GlyH-101)–inhibited currents in CF animals due to the lack of CFTR. CFTR mRNA was present throughout all levels of the WT ferret and IBMX/forskolin–inducible ISC was only observed in WT animals. However, despite the lack of CFTR function in the knockout ferret, the luminal pH of the CF ferret gallbladder, stomach, and intestines was not significantly changed relative to WT. The WT stomach and gallbladder exhibited significantly enhanced IBMX/forskolin ISC responses and inhibition by GlyH-101 relative to CF samples. These findings demonstrate that multiple organs affected by disease in the CF ferret have bioelectric abnormalities consistent with the lack of cAMP-mediated chloride transport. PMID:23782101

  18. Outcomes of adoption of adult laboratory ferrets after gonadectomy during a veterinary student teaching exercise.

    PubMed

    Harms, Craig A; Stoskopf, Michael K

    2007-07-01

    We surveyed 27 people who had adopted a total of 43 adult domestic ferrets after their use in a series of veterinary student surgery teaching laboratories to assess the success of those adoptions and to determine the rate of occurrence of common maladies of domestic ferrets after adult gonadectomy as compared with the usual practice of early-age gonadectomy. The adoptions took place 1-7 y prior to the survey. The response rate was 48% of adopters, covering 53% of the ferrets. Overall the success of former breeding and instructional ferrets as pets were rated as 91% good or excellent and 4.5% poor. Behavioral issues (for example, nipping, failure to litter train) were noted as the most common problems (36% of ferrets). Adrenal gland disease, insulinoma, or lymphosarcoma occurred in 23% of all ferrets and accounted for 57% of those ferrets that had died prior to the time of the survey. PMID:17645296

  19. Resource selection by black-footed ferrets in South Dakota and Montana

    USGS Publications Warehouse

    Jachowski, D.S.; Millspaugh, J.J.; Biggins, D.E.; Livieri, T.M.; Matchett, M.R.; Rittenhouse, C.D.

    2011-01-01

    The black-footed ferret (Mustela nigripes), once extinct in the wild, remains one of the most critically endangered mammals in North America despite 18 years of reintroduction attempts. Because black-footed ferrets are specialized predators of prairie dogs (Cynomys sp.), a better understanding of how black-footed ferrets select resources might provide insight into how best to identify and manage reintroduction sites. We monitored ferret resource selection at two reintroduction sites with different densities of prairie dog populations-one that contained a high density of prairie dogs (Conata Basin, South Dakota) and one that was lower (UL Bend, Montana). We evaluated support for hypotheses about ferret resource selection as related to the distribution of active burrows used by black-tailed prairie dogs (Cynomys ludovicianus), interactions between ferrets, and habitat edge effects. We found support for all three factors within both populations; however, they affected ferret resource selection differently at each site. Ferrets at Conata Basin tended to select areas with high prairie dog burrow density, closer to the colony edge, and that overlapped other ferret ranges. In contrast, ferrets at UL Bend tended not to select areas of high active prairie dog burrow density, avoided areas close to edge habitat, and females avoided areas occupied by other ferrets. The differences observed between the two sites might be best explained by prairie dog densities, which were higher at Conata Basin (119.3 active burrows per ha) than at UL Bend (44.4 active burrows per ha). Given the positive growth of ferret populations at Conata Basin, management that increases the density of prairie dogs might enhance ferret success within natural areas. To achieve long-term recovery of ferrets in the wild, conservationists should increasingly work across and outside natural area boundaries to increase prairie dog populations.

  20. Transient diabetes mellitus in a domestic ferret (Mustela putorius furo)

    PubMed Central

    Duhamelle, Alexis; Langlois, Isabelle; Desmarchelier, Marion

    2015-01-01

    A 3.5-year-old spayed female ferret, fed a diet high in refined sugar, was referred for lethargy, polyuria, polydipsia, and polyphagia. Diabetic ketoacidosis was diagnosed. Treatment included insulin therapy and a low carbohydrate diet. Diabetes mellitus resolved 54 d later, and insulin therapy was discontinued. There has been no recurrence of the diabetes mellitus. PMID:26130836

  1. A Ferret-based gastrointestinal image retrieval system.

    PubMed

    Bedrick, Steven; Kalpathy-Cramer, Jayashree

    2007-01-01

    We developed a web-based interface for image retrieval and cluster analysis system. The system handles search queries using Ferret, a port to the Ruby language of the Apache Lucene indexing and searching system. The system uses de-identified endoscopic images from the Clinical Outcomes Research Initiative data repository, and is designed for use by students and researchers.

  2. Landscape features influence postrelease predation on endangered black-footed ferrets

    USGS Publications Warehouse

    Poessel, S.A.; Breck, S.W.; Biggins, D.E.; Livieri, T.M.; Crooks, K.R.; Angeloni, L.

    2011-01-01

    Predation can be a critical factor influencing recovery of endangered species. In most recovery efforts lethal and nonlethal influences of predators are not sufficiently understood to allow prediction of predation risk, despite its importance. We investigated whether landscape features could be used to model predation risk from coyotes (Canis latrans) and great horned owls (Bubo virginianus) on the endangered black-footed ferret (Mustela nigripes). We used location data of reintroduced ferrets from 3 sites in South Dakota to determine whether exposure to landscape features typically associated with predators affected survival of ferrets, and whether ferrets considered predation risk when choosing habitat near perches potentially used by owls or near linear features predicted to be used by coyotes. Exposure to areas near likely owl perches reduced ferret survival, but landscape features potentially associated with coyote movements had no appreciable effect on survival. Ferrets were located within 90 m of perches more than expected in 2 study sites that also had higher ferret mortality due to owl predation. Densities of potential coyote travel routes near ferret locations were no different than expected in all 3 sites. Repatriated ferrets might have selected resources based on factors other than predator avoidance. Considering an easily quantified landscape feature (i.e., owl perches) can enhance success of reintroduction efforts for ferrets. Nonetheless, development of predictive models of predation risk and management strategies to mitigate that risk is not necessarily straightforward for more generalist predators such as coyotes. ?? 2011 American Society of Mammalogists.

  3. Black-footed ferrets and Siberian polecats as ecological surrogates and ecological equivalents

    USGS Publications Warehouse

    Biggins, D.E.; Hanebury, L.R.; Miller, B.J.; Powell, R.A.

    2011-01-01

    Ecologically equivalent species serve similar functions in different communities, and an ecological surrogate species can be used as a substitute for an equivalent species in a community. Siberian polecats (Mustela eversmanii) and black-footed ferrets (M. nigripes) have long been considered ecological equivalents. Polecats also have been used as investigational surrogates for black-footed ferrets, yet the similarities and differences between the 2 species are poorly understood. We contrasted activity patterns of radiotagged polecats and ferrets released onto ferret habitat. Ferrets tended to be nocturnal and most active after midnight. Polecats were not highly selective for any period of the day or night. Ferrets and polecats moved most during brightly moonlit nights. The diel activity pattern of ferrets was consistent with avoidance of coyotes (Canis latrans) and diurnal birds of prey. Similarly, polecat activity was consistent with avoidance of red foxes (Vulpes vulpes) in their natural range. Intraguild predation (including interference competition) is inferred as a selective force influencing behaviors of these mustelines. Examination of our data suggests that black-footed ferrets and Siberian polecats might be ecological equivalents but are not perfect surrogates. Nonetheless, polecats as surrogates for black-footed ferrets have provided critical insight needed, especially related to predation, to improve the success of ferret reintroductions. ?? 2011 American Society of Mammalogists.

  4. Molecular analysis of neocortical layer structure in the ferret

    PubMed Central

    Rowell, Joanna J.; Mallik, Atul K.; Dugas-Ford, Jennifer; Ragsdale, Clifton W.

    2010-01-01

    Molecular markers that distinguish specific layers of rodent neocortex are increasingly employed to study cortical development and the physiology of cortical circuits. The extent to which these markers represent general features of neocortical cell type identity across mammals is, however, unknown. To assess the conservation of layer markers more broadly, we isolated orthologs for fifteen layer-enriched genes in the ferret, a carnivore with a large, gyrencephalic brain, and analyzed their patterns of neocortical gene expression. Our major findings are: (1) Many but not all layer markers tested show similar patterns of layer-specific gene expression between mouse and ferret cortex, supporting the view that layer-specific cell type identity is conserved at a molecular level across mammalian superorders; (2) Our panel of deep layer markers (ER81/ETV1, SULF2, PCP4, FEZF2/ZNF312, CACNA1H, KCNN2/SK2, SYT6, FOXP2, CTGF) provides molecular evidence that the specific stratifications of layer 5 and 6 into 5a, 5b, 6a and 6b are also conserved between rodents and carnivores. (3) Variations in layer-specific gene expression are more pronounced across areas of ferret cortex than between homologous areas of mouse and ferret cortex; (4) This variation of area gene expression was clearest with the superficial layer markers studied (SERPINE2, MDGA1, CUX1, UNC5D, RORB/NR1F2, EAG2/KCNH5). Most dramatically, the layer 4 markers RORB and EAG2 disclosed a molecular sublamination to ferret visual cortex and demonstrated a molecular dissociation among the so-called agranular areas of the neocortex. Our findings establish molecular markers as a powerful complement to cytoarchitecture for neocortical layer and cell-type comparisons across mammals. PMID:20575059

  5. Cryptococcus gattii infection in a Spanish pet ferret (Mustela putorius furo) and asymptomatic carriage in ferrets and humans from its environment.

    PubMed

    Morera, Neus; Juan-Sallés, Carles; Torres, Josep M; Andreu, Mariano; Sánchez, Manuel; Zamora, María Ángeles; Colom, M Francisca

    2011-10-01

    A domestic ferret (Mustela putorius furo) was presented with lymphadenopathy and acute bilateral blindness. Cytologic evaluation and biopsy of an affected lymph node revealed pyogranulomatous lymphadenitis with intralesional yeast consistent with Cryptococcus sp. Subsequent studies demonstrated Cryptococcus gattii serotype B VGI/AFLP4 as the causative agent. The ferret was treated with fluconazole and prednisone. After one month of therapy, an improvement of the clinical symptoms was detected although blindness persisted. Seven months after presentation, the disease progressed to a severe neurologic condition, and it was euthanized. Postmortem exam revealed disseminated cryptococcosis with prominent neurologic involvement. Nasal swabs of other ferrets and humans from the same household revealed that two ferrets and two humans to be asymptomatic carriers of the same strain of cryptococcus as the necropsied ferret. These findings stress the importance of veterinary diagnostic work with pets and epidemiological investigations for disease prevention in them and in their owners. PMID:21395475

  6. Effects of experience and cage enrichment on predatory skills of black-footed ferrets (Mustela nigripes)

    USGS Publications Warehouse

    Vargas, A.; Anderson, S.H.

    1999-01-01

    We studied ontogeny of predatory skills of growing black-footed ferrets (Mustela nigripes) raised under different captive conditions. To test effects of maturation, experience, and cage enrichment on predatory behavior, we exposed 70 juvenile black-footed ferrets to different numbers of live hamsters (Mesocricetus auratus) throughout development. Both maturation and experience increased the likelihood of a black-footed ferret making a successful kill. Black-footed ferrets exposed to greater environmental complexity (enriched cage, including encouragement of food-searching behaviors) also were more likely to kill than ferrets raised in a deprived environment. Behavioral studies of captive-raised black-footed ferrets can help refine current breeding techniques and ultimately enhance efforts to recover this endangered carnivore.

  7. Neuronal Migration Dynamics in the Developing Ferret Cortex

    PubMed Central

    Gertz, Caitlyn C.

    2015-01-01

    During mammalian neocortical development, newborn excitatory and inhibitory neurons must migrate over long distances to reach their final positions within the cortical plate. In the lissencephalic rodent brain, pyramidal neurons are born in the ventricular and subventricular zones of the pallium and migrate along radial glia fibers to reach the appropriate cortical layer. Although much less is known about neuronal migration in species with a gyrencephalic cortex, retroviral studies in the ferret and primate suggest that, unlike the rodent, pyramidal neurons do not follow strict radial pathways and instead can disperse horizontally. However, the means by which pyramidal neurons laterally disperse remain unknown. In this study, we identified a viral labeling technique for visualizing neuronal migration in the ferret, a gyrencephalic carnivore, and found that migration was predominantly radial at early postnatal ages. In contrast, neurons displayed more tortuous migration routes with a decreased frequency of cortical plate-directed migration at later stages of neurogenesis concomitant with the start of brain folding. This was accompanied by neurons migrating sequentially along several different radial glial fibers, suggesting a mode by which pyramidal neurons may laterally disperse in a folded cortex. These findings provide insight into the migratory behavior of neurons in gyrencephalic species and provide a framework for using nonrodent model systems for studying neuronal migration disorders. SIGNIFICANCE STATEMENT Elucidating neuronal migration dynamics in the gyrencephalic, or folded, cortex is important for understanding neurodevelopmental disorders. Similar to the rodent, we found that neuronal migration was predominantly radial at early postnatal ages in the gyrencephalic ferret cortex. Interestingly, ferret neurons displayed more tortuous migration routes and a decreased frequency of radial migration at later ages coincident with the start of cortical folding

  8. Movements and survival of black-footed ferrets associated with an experimental translocation in South Dakota

    USGS Publications Warehouse

    Biggins, D.E.; Godbey, J.L.; Horton, B.M.; Livieri, T.M.

    2011-01-01

    Black-footed ferrets (Mustela nigripes) apparently were extirpated from all native habitats by 1987, and their repatriation requires a combination of captive breeding, reintroductions, and translocations among sites. Improvements in survival rates of released ferrets have resulted from experience in quasi-natural environments during their rearing. Reestablishment of a self-sustaining wild population by 1999 provided the 1st opportunity to initiate new populations by translocating wild-born individuals. Using radiotelemetry, we compared behaviors and survival of 18 translocated wild-born ferrets and 18 pen-experienced captive-born ferrets after their release into a prairie dog colony not occupied previously by ferrets. Translocated wild-born ferrets moved significantly less and had significantly higher short-term survival rates than their captive-born counterparts. Using markrecapture methods, we also assessed potential impacts to the established donor population of removing 37% of its estimated annual production of kits. Annual survival rates for 30 ferret kits remaining at the donor subcomplex were higher than rates for 54 ferret kits at the control subcomplex (unmanipulated) for males (+82%) and females (+32%). Minimum survival of translocated kits did not differ significantly from survival of those at the control subcomplex. Direct translocation of young, wild-born ferrets from site to site appears to be an efficient method to establish new populations. ?? 2011 American Society of Mammalogists.

  9. Isolation, Characterization, and Functional Analysis of Ferret Lymphatic Endothelial Cells

    PubMed Central

    Berendam, Stella J.; Fallert-Junecko, Beth A.; Murphy-Corb, Michael A.; Fuller, Deborah H.; Reinhart, Todd A.

    2014-01-01

    The lymphatic endothelium (LE) serves as a conduit for transport of immune cells and soluble antigens from peripheral tissues to draining lymph nodes (LNs), contributing to development of host immune responses and possibly dissemination of microbes. Lymphatic endothelial cells (LECs) are major constituents of the lymphatic endothelium. These specialized cells could play important roles in initiation of host innate immune responses through sensing of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), including toll-like receptors (TLRs). LECs secrete pro-inflammatory cytokines and chemokines to create local inflammatory conditions for recruitment of naïve antigen presenting cells (APCs) such as dendritic cells (DCs) to sites of infection and/or vaccine administration. In this study, we examined the innate immune potential of primary LEC populations derived from multiple tissues of an animal model for human infectious diseases -- the ferret. We generated a total of six primary LEC populations from lung, tracheal, and mesenteric LN tissues from three different ferrets. Standard RT-PCR characterization of these primary LECs showed that they varied in their expression of LEC markers. The ferret LECs were examined for their ability to respond to poly I:C (TLR3 and RIG-1 ligand) and other known TLR ligands as measured by production of proinflammatory cytokine (IFNα, IL6, IL10, Mx1, and TNFα) and chemokine (CCL5, CCL20, and CXCL10) mRNAs using real time RT-PCR. Poly I:C exposure induced robust proinflammatory responses by all of the primary ferret LECs. Chemotaxis was performed to determine the functional activity of CCL20 produced by the primary lung LECs and showed that the LEC-derived CCL20 was abundant and functional. Taken together, our results continue to reveal the innate immune potential of primary LECs during pathogen-host interactions and expand our understanding of the roles of LECs might play in health and disease in

  10. Gastrointestinal Pathology in Juvenile and Adult CFTR-Knockout Ferrets

    PubMed Central

    Sun, Xingshen; Olivier, Alicia K.; Yi, Yaling; Pope, Christopher E.; Hayden, Hillary S.; Liang, Bo; Sui, Hongshu; Zhou, Weihong; Hager, Kyle R.; Zhang, Yulong; Liu, Xiaoming; Yan, Ziying; Fisher, John T.; Keiser, Nicholas W.; Song, Yi; Tyler, Scott R.; Goeken, J. Adam; Kinyon, Joann M.; Radey, Matthew C.; Fligg, Danielle; Wang, Xiaoyan; Xie, Weiliang; Lynch, Thomas J.; Kaminsky, Paul M.; Brittnacher, Mitchell J.; Miller, Samuel I.; Parekh, Kalpaj; Meyerholz, David K.; Hoffman, Lucas R.; Frana, Timothy; Stewart, Zoe A.; Engelhardt, John F.

    2015-01-01

    Cystic fibrosis (CF) is a multiorgan disease caused by loss of a functional cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel in many epithelia of the body. Here we report the pathology observed in the gastrointestinal organs of juvenile to adult CFTR-knockout ferrets. CF gastrointestinal manifestations included gastric ulceration, intestinal bacterial overgrowth with villous atrophy, and rectal prolapse. Metagenomic phylogenetic analysis of fecal microbiota by deep sequencing revealed considerable genotype-independent microbial diversity between animals, with the majority of taxa overlapping between CF and non-CF pairs. CF hepatic manifestations were variable, but included steatosis, necrosis, biliary hyperplasia, and biliary fibrosis. Gallbladder cystic mucosal hyperplasia was commonly found in 67% of CF animals. The majority of CF animals (85%) had pancreatic abnormalities, including extensive fibrosis, loss of exocrine pancreas, and islet disorganization. Interestingly, 2 of 13 CF animals retained predominantly normal pancreatic histology (84% to 94%) at time of death. Fecal elastase-1 levels from these CF animals were similar to non-CF controls, whereas all other CF animals evaluated were pancreatic insufficient (<2 μg elastase-1 per gram of feces). These findings suggest that genetic factors likely influence the extent of exocrine pancreas disease in CF ferrets and have implications for the etiology of pancreatic sufficiency in CF patients. In summary, these studies demonstrate that the CF ferret model develops gastrointestinal pathology similar to CF patients. PMID:24637292

  11. Behavioral Measures of Auditory Streaming in Ferrets (Mustela putorius)

    PubMed Central

    Ma, Ling; Yin, Pingbo; Micheyl, Christophe; Oxenham, Andrew J.; Shamma, Shihab A.

    2015-01-01

    An important aspect of the analysis of auditory “scenes” relates to the perceptual organization of sound sequences into auditory “streams.” In this study, we adapted two auditory perception tasks, used in recent human psychophysical studies, to obtain behavioral measures of auditory streaming in ferrets (Mustela putorius). One task involved the detection of shifts in the frequency of tones within an alternating tone sequence. The other task involved the detection of a stream of regularly repeating target tones embedded within a randomly varying multitone background. In both tasks, performance was measured as a function of various stimulus parameters, which previous psychophysical studies in humans have shown to influence auditory streaming. Ferret performance in the two tasks was found to vary as a function of these parameters in a way that is qualitatively consistent with the human data. These results suggest that auditory streaming occurs in ferrets, and that the two tasks described here may provide a valuable tool in future behavioral and neurophysiological studies of the phenomenon. PMID:20695663

  12. A ferret model of COPD-related chronic bronchitis

    PubMed Central

    Raju, S. Vamsee; Kim, Hyunki; Byzek, Stephen A.; Tang, Li Ping; Trombley, John E.; Jackson, Patricia; Rasmussen, Lawrence; Wells, J. Michael; Libby, Emily Falk; Winter, Lindy; Samuel, Sharon L.; Zinn, Kurt R.; Blalock, J. Edwin; Schoeb, Trenton R.; Dransfield, Mark T.; Rowe, Steven M.

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US. The majority of COPD patients have symptoms of chronic bronchitis, which lacks specific therapies. A major impediment to therapeutic development has been the absence of animal models that recapitulate key clinical and pathologic features of human disease. Ferrets are well suited for the investigation of the significance of respiratory diseases, given prior data indicating similarities to human airway physiology and submucosal gland distribution. Here, we exposed ferrets to chronic cigarette smoke and found them to approximate complex clinical features of human COPD. Unlike mice, which develop solely emphysema, smoke-exposed ferrets exhibited markedly higher numbers of early-morning spontaneous coughs and sporadic infectious exacerbations as well as a higher level of airway obstruction accompanied by goblet cell metaplasia/hyperplasia and increased mucus expression in small airways, indicative of chronic bronchitis and bronchiolitis. Overall, we demonstrate the first COPD animal model exhibiting clinical and pathologic features of chronic bronchitis to our knowledge, providing a key advance that will greatly facilitate the preclinical development of novel treatments for this disease. PMID:27699245

  13. The pathogenesis of respiratory syncytial virus infection in infant ferrets.

    PubMed Central

    Prince, G. A.; Porter, D. D.

    1976-01-01

    The infant ferret is susceptible to respiratory syncytial virus infection in both the upper and lower respiratory tracts. In the nose, viral replication is restricted to the surface respiratory epithelium in the nasal passages and turbinates. In the lungs, viral replication is of a lower order of magnitude and is localized in the alveolar cells. The pattern of viral replication in nasal tissues is independent of the age of the animal at infection, whereas the pattern in lung tissues shows a striking age dependence, with viral replication progressively decreasing as a function of age. Thes age dependence appears to be due to an intrinsic age-related mechanism yet to be defined. We feel that the infant ferret is an acceptable model for the study of respiratory syncytial virus disease and that the study of age dependence observed in ferrets may allow elucidation of the mechanisms involved in the age dependence seen in humans. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1251889

  14. Characterization of radiation-induced emesis in the ferret

    SciTech Connect

    King, G.L.

    1988-01-01

    Forty-eight ferrets (Mustela putorius furo) were individually head-shielded and radiated with bilateral cobalt 60 gamma radiation at 100 cGy min at doses ranging between 49 and 601 cGy. The emetic threshold was observed at 69 cGy, the ED 50 was calculated as 77 cGy, and 100% incidence of emesis occurred at 201 cGy. With increasing doses of radiation, the latency to first emesis after radiation decreased dramatically, whereas the duration of the prodromal period increased. Two other sets of experiments suggest that dopaminergic mechanisms play a minor role in radiation-induced emesis in the ferret. Twenty-two animals were injected either intravenously or subcutaneously with 30 to 300 micrograms /kg of apomorphine. Fewer than 50% of the animals vomited to 300 micrograms/kg apomorphine; central dopaminergic receptor activation was apparent at all doses. Another eight animals received 1 mg/kg domperidone prior to either 201 (n=4) or 401 (n=4) cGy radiation and their emetic responses were compared with NaCi-injected-irradiated controls (n=8). At 201 cGy, domperidone significantly reduced only the total time in emetic behavior. At 401 cGy, domperidone had no salutary effect on radiation-induced emesis. The emetic responses of the ferret to radiation and apomorphine are compared with these responses in other vomiting species.

  15. A ferret model of COPD-related chronic bronchitis

    PubMed Central

    Raju, S. Vamsee; Kim, Hyunki; Byzek, Stephen A.; Tang, Li Ping; Trombley, John E.; Jackson, Patricia; Rasmussen, Lawrence; Wells, J. Michael; Libby, Emily Falk; Winter, Lindy; Samuel, Sharon L.; Zinn, Kurt R.; Blalock, J. Edwin; Schoeb, Trenton R.; Dransfield, Mark T.; Rowe, Steven M.

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US. The majority of COPD patients have symptoms of chronic bronchitis, which lacks specific therapies. A major impediment to therapeutic development has been the absence of animal models that recapitulate key clinical and pathologic features of human disease. Ferrets are well suited for the investigation of the significance of respiratory diseases, given prior data indicating similarities to human airway physiology and submucosal gland distribution. Here, we exposed ferrets to chronic cigarette smoke and found them to approximate complex clinical features of human COPD. Unlike mice, which develop solely emphysema, smoke-exposed ferrets exhibited markedly higher numbers of early-morning spontaneous coughs and sporadic infectious exacerbations as well as a higher level of airway obstruction accompanied by goblet cell metaplasia/hyperplasia and increased mucus expression in small airways, indicative of chronic bronchitis and bronchiolitis. Overall, we demonstrate the first COPD animal model exhibiting clinical and pathologic features of chronic bronchitis to our knowledge, providing a key advance that will greatly facilitate the preclinical development of novel treatments for this disease.

  16. Postbreeding resource selection by adult black-footed ferrets in the Conata Basin, South Dakota

    USGS Publications Warehouse

    Eads, D.A.; Millspaugh, J.J.; Biggins, D.E.; Livieri, T.M.; Jachowski, D.S.

    2011-01-01

    We investigated postbreeding resource selection by adult black-footed ferrets (Mustela nigripes) on a 452-ha black-tailed prairie dog (Cynomys ludovicianus) colony in the Conata Basin of South Dakota during 20072008. We used resource selection functions (RSFs) to evaluate relationships between numbers of ferret locations and numbers of prairie dog burrow openings (total or active), distances to colony edges, and connectivity of patches of burrow openings. In both years ferrets selected areas near edges of the prairie dog colony where active burrow openings were abundant. In the interior of the colony ferrets selected areas with low abundance of active burrow openings. At times, prairie dog productivity (i.e., pup abundance) might be greatest at colony edges often characterized by grasses; ferrets are likely to select areas where refuge and vulnerable prey are abundant. Ferrets could have used interior areas with few active burrow openings as corridors between edge areas with many active burrow openings. Also, in areas with few active burrow openings ferrets spend more time aboveground during movements and, thus, are likely to be more easily detected. These results complement previous studies demonstrating importance of refuge and prey in fine-scale resource selection by ferrets and provide insight into factors that might influence edge effects on ferret space use. Conservation and restoration of colonies with areas with high densities of burrow openings and prairie dogs, and corridors between such areas, are needed for continued recovery of the black-footed ferret. RSFs could complement coarse-scale habitat evaluations by providing finer-scale assessments of habitat for the black-footed ferret. ?? 2011 American Society of Mammalogists.

  17. Fine-scale habitat use of reintroduced black-footed ferrets on prairie dog colonies in New Mexico

    USGS Publications Warehouse

    Chipault, Jennifer G.; Biggins, Dean E.; Detling, James K.; Long, Dustin H.; Reich, Robin M.

    2012-01-01

    Black-footed ferrets (Mustela nigripes) are among the most endangered animals in North America. Reintroductions of captive-born ferrets onto prairie dog (Cynomys spp.) colonies are crucial to the conservation of the species. In September 2007, captive-born ferrets were released on a black-tailed prairie dog (Cynomys ludovicianus) colony at the Vermejo Park Ranch, New Mexico. Ferret kits experimentally released in areas of comparatively low and high prairie dog burrow densities were located via spotlight surveys. Some maturing ferret kits were subsequently translocated to areas of low and high burrow densities on nearby prairie dog colonies. For 2 months, fine-scale habitat use was quantified by mapping all burrow openings within a 30-m radius of each ferret location. Spatial statistics accounted for autocorrelation in the burrow densities in areas used by ferrets. It was hypothesized that ferrets would select areas of high burrow densities within colonies; however, burrow densities in areas used by ferrets were generally similar to the available burrow densities. Because ferrets used areas with burrow densities similar to densities available at the colony level and because of the potential energetic benefits for ferrets using areas with high burrow densities, releasing ferrets on colonies with high burrow densities might increase reintroduction success.

  18. Fatal vaccine-induced canine distemper virus infection in black-footed ferrets

    USGS Publications Warehouse

    Carpenter, J.W.; Appel, M.J.G.; Erickson, R.C.; Novilla, M.N.

    1976-01-01

    Four black-footed ferrets that were live-trapped in South Dakota and transported to the Patuxent Wildlife Research Center died within 21 days after vaccination with modified live canine distemper virus. Immunofluorescence, European ferret inoculation, virus isolation attempts, and serum-neutralization tests indicated insufficient attenuation of the vaccine for this species.

  19. First Case of Systemic Coronavirus Infection in a Domestic Ferret (Mustela putorius furo) in Peru.

    PubMed

    Lescano, J; Quevedo, M; Gonzales-Viera, O; Luna, L; Keel, M K; Gregori, F

    2015-12-01

    A domestic ferret from Lima, Peru, died after ten days of non-specific clinical signs. Based on pathology, immunohistochemistry and molecular analysis, ferret systemic coronavirus (FRSCV)-associated disease was diagnosed for the first time in South America. This report highlights the potential spread of pathogens by the international pet trade.

  20. The draft genome sequence of the ferret (Mustela putorius furo) facilitates study of human respiratory disease

    PubMed Central

    Peng, Xinxia; Alföldi, Jessica; Gori, Kevin; Eisfeld, Amie J.; Tyler, Scott R.; Tisoncik-Go, Jennifer; Brawand, David; Law, G. Lynn; Skunca, Nives; Hatta, Masato; Gasper, David J.; Kelly, Sara M.; Chang, Jean; Thomas, Matthew J.; Johnson, Jeremy; Berlin, Aaron M.; Lara, Marcia; Russell, Pamela; Swofford, Ross; Turner-Maier, Jason; Young, Sarah; Hourlier, Thibaut; Aken, Bronwen; Searle, Steve; Sun, Xingshen; Yi, Yaling; Suresh, M.; Tumpey, Terrence M.; Siepel, Adam; Wisely, Samantha M.; Dessimoz, Christophe; Kawaoka, Yoshihiro; Birren, Bruce W.; Lindblad-Toh, Kerstin; Di Palma, Federica; Engelhardt, John F.; Palermo, Robert E.; Katze, Michael G.

    2014-01-01

    The domestic ferret (Mustela putorius furo) is an important animal model for multiple human respiratory diseases. It is considered the ‘gold standard’ for modeling human influenza virus infection and transmission1–4. Here we describe the 2.41 Gb draft genome assembly of the domestic ferret, constituting 2.28 Gb of sequence plus gaps. We annotate 19,910 protein-coding genes on this assembly using RNA-seq data from 21 ferret tissues. We characterize the ferret host response to two influenza virus infections by RNA-seq analysis of 42 ferret samples from influenza time courses, and show distinct signatures in ferret trachea and lung tissues specific to 1918 or 2009 human pandemic influenza virus infections. Using microarray data from 16 ferret samples reflecting cystic fibrosis (CF) disease progression, we show that transcriptional changes in the CFTR-knockout ferret lung reflect pathways of early disease that cannot be readily studied in human infants with CF disease. PMID:25402615

  1. 78 FR 23948 - Endangered and Threatened Wildlife and Plants; Black-Footed Ferret Draft Recovery Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ... America wherever prairie dogs occurred. The species was listed as endangered in 1967 (32 FR 4001; March 11... Species Conservation Act of 1969 (35 FR 8491; June 2, 1970). On January 4, 1974, the black-footed ferret was listed under the Endangered Species Act of 1973 (39 FR 1171). The ferret's close association...

  2. Morning ambush attacks by black-footed ferrets on emerging prairie dogs

    USGS Publications Warehouse

    Eads, D.A.; Biggins, D.E.; Jachowski, D.S.; Livieri, T.M.; Millspaugh, J.J.; Forsberg, M.

    2010-01-01

    Black-footed ferrets (Mustela nigripes) often hunt at night, attacking normally diurnal prairie dogs (Cynomys spp.) in underground burrow systems. While monitoring black-footed ferrets in South Dakota during morning daylight hours, we observed an adult female ferret ambush a black-tailed prairie dog (C. ludovicianus) emerging from a burrow. On a neighboring colony, we observed a second adult female ferret engaging in similar ambush behaviors on 12 occasions, although prey was not visible. We retrospectively assessed radio-telemetry data on white-tailed prairie dogs (C. leucurus) and a male and a female ferret to evaluate ferret activity in relation to timing of prairie dog emergence. Activity of radio-collared ferrets was high during the hourly period when prairie dogs first emerged and the following 2 hr, relative to later daylight hours. Such behavior is consistent with behaviors observed in South Dakota. Nighttime movements by ferrets might involve hunting but also reconnaissance of prey preparatory to morning ambush attacks.

  3. Use of multi-opening burrow systems by black-footed ferrets

    USGS Publications Warehouse

    Biggins, Dean E.

    2012-01-01

    Multi-opening burrow systems constructed by prairie dogs (Cynomys) ostensibly provide escape routes when prairie dogs are pursued by predators capable of entering the burrows, such as black-footed ferrets (Mustela nigripes), or by predators that can rapidly dig into the tunnels, such as American badgers (Taxidea taxus). Because badgers also prey on ferrets, ferrets might similarly benefit from multi-opening burrow systems. Using an air blower, white-tailed prairie dog (Cynomys leucurus) burrow openings were tested for connectivity on plots occupied by black-footed ferrets and on randomly selected plots in Wyoming. Significantly more connected openings were found on ferret-occupied plots than on random plots. Connected openings might be due to modifications by ferrets in response to plugging by prairie dogs, due to selection by ferrets for complex systems with multiple openings that are already unobstructed, or simply due to ferrets lingering at kill sites that were multi-opening systems selected by their prairie dog prey.

  4. Rhinitis and disseminated disease in a ferret (Mustela putorius futo) naturally infected with Sarcocystis neurona

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Naturally occurring Sarcocystis neurona infection in a ferret (Mustela putorius futo) with rhinitis and disseminated disease are described for the first time. The ferret exhibited severe rhinitis with intra-lesional S. neurona merozoites and schizonts. Diagnosis was confirmed immunohistochemically b...

  5. Rabies Virus Infection in Ferret Badgers (Melogale moschata subaurantiaca) in Taiwan: A Retrospective Study.

    PubMed

    Chang, Jen-Chieh; Tsai, Kuo-Jung; Hsu, Wei-Cheng; Tu, Yang-Chang; Chuang, Wei-Chieh; Chang, Chia-Yi; Chang, Shih-Wei; Lin, Te-En; Fang, Kuo-Yun; Chang, Yung-Fu; Tsai, Hsiang-Jung; Lee, Shu-Hwae

    2015-10-01

    Fifteen ferret badgers (Melogale moschata subaurantiaca), collected 2010-13 and stored frozen, were submitted for rabies diagnosis by direct fluorescent antibody test and reverse transcription PCR. We detected seven positive animal samples, including some from 2010, which indicated that the ferret badger population in Taiwan had been affected by rabies prior to 2010.

  6. Rehabilitation of a Species: The Black-Footed Ferret (Mustela nigripes)

    USGS Publications Warehouse

    Miller, Brian; Biggins, Dean E.; Hanebury, Lou; Conway, Courtney; Wemmer, Chris

    1991-01-01

    Black-footed ferrets (Mustela nigripes) are an endangered carnivore endemic to North America.  This small nocturnal member of the weasel family is totally dependent on the prairie dog (Cynomys spp.) ecosystem for survival.  The ferret lives in prairie dog burrows and relies on prairie dogs for 90 percent of its diet (3,21).  Poisoning of prairie dogs was largely responsible for the 98 percent reduction in geographic distribution of prairie dogs; concurrently, black-footed ferret numbers plummeted.  Recently, only a single known population of black-footed ferrets remained.  In 1985 that popuation, located near Meeteetse Wyoming, succumbed to an outbreak of canine distemper, and the few remaining ferrets were taken into captivity in an attempt to save the species through captive progation.

  7. Identification of a tyrosinase (TYR) exon 4 deletion in albino ferrets (Mustela putorius furo).

    PubMed

    Blaszczyk, W M; Distler, C; Dekomien, G; Arning, L; Hoffmann, K-P; Epplen, J T

    2007-08-01

    Albinism is due to a lack of pigmentation in hair, skin and eye, and has been shown to occur in several animal species. Mutations of the tyrosinase (TYR) gene account for albinism in domestic cats, rabbits, cattle, mice and rats. In this study, we demonstrate that a TYR mutation accounts for albinism in the ferret (Mustela putorius furo). The coding sequence of the five exons of TYR was determined in genomic DNA from wild-type pigmented 'sable' coloured and albino ferrets. It was not possible to amplify TYR exon 4 in albino ferrets originating from different breeds. The deletion of exon 4 in albino ferrets was confirmed by Southern blot hybridization of genomic DNA from albino and pigmented ferrets. This is the first report of a deletion of a TYR exon in a non-human mammal. PMID:17655555

  8. Issues to consider for preparing ferrets as research subjects in the laboratory.

    PubMed

    Ball, Roberta Scipioni

    2006-01-01

    The domestic or European ferret (Mustela putorius furo) has been domesticated for thousands of years. Ferrets have been used for hunting and fur production, as pets, and as models in biomedical research. Despite the relatively small numbers used in the laboratory, ferrets have some unique applications including study of human influenza and severe acute respiratory syndrome (SARS)-associated corona virus. They have served as models for peptic ulcer disease, carotenoid metabolism, cystic fibrosis, and drug emesis screening, among others. Most research ferrets are males, due to estrus-related health problems in females. They may be housed conventionally and are easy to care for when their biology and behavior are understood. Due to the small number of ferret suppliers, animals are often shipped long distances, requiring air transport and intermediate handlers. It is important to minimize shipment stress, especially with weanling and pregnant animals. Additional expertise is required for success with pregnant and whelping ferrets and for rearing of neonates. The animals have specific dietary requirements, and proper nutrition is key. Successful housing requires knowledge of ferret behaviors including social behavior, eating habits, a general inquisitive nature, and a species-typical need to burrow and hide. Regular handling is necessary to maintain well-being. A ferret health care program consists of physical examination, immunization, clinical pathology, and a working knowledge of common ferret diseases. Various research methodologies have been described, from basic procedures such as blood collection to major invasive survival surgery. Ferrets have a distinct niche in biomedical research and are hardy animals that thrive well in the laboratory. PMID:16963814

  9. American badgers selectively excavate burrows in areas used by black-footed ferrets: implications for predator avoidance

    USGS Publications Warehouse

    Eads, David A.; Biggins, Dean E.; Livieri, Travis M.; Millspaugh, Joshua J.

    2013-01-01

    We evaluated how American badgers (Taxidea taxus) might exert selective pressure on black-footed ferrets (Mustela nigripes) to develop antipredator defenses. In a colony of black-tailed prairie dogs (Cynomys ludovicianus) in South Dakota, badgers concentrated their activities where burrow openings and prairie dogs were abundant, a selective behavior that was exhibited by ferrets in the same colony. Badgers excavated burrows more often when in areas recently used by a ferret, suggesting that badgers hunt ferrets or steal prey from ferrets, or both. We also conducted an analysis of survival studies for ferrets and Siberian polecats (M. eversmanii) released onto prairie dog colonies. This polecat is the ferret's ecological equivalent but evolved without a digging predator. Badgers accounted for 30.0% of predation on polecats and 5.5% of predation on ferrets. In contrast, both polecats and ferrets have evolutionary experience with canids, providing a plausible explanation for the similar relative impact of coyotes (Canis latrans) on them (65.0% and 67.1% of predation, respectively). We hypothesize that ferrets and badgers coexist because ferrets are superior at exploitation competition and are efficient at avoiding badgers, and badgers are superior at interference competition.

  10. Patterns of surface plugging in a colony of black-tailed prairie dogs occupied by black-footed ferrets

    USGS Publications Warehouse

    Eads, David E.; Biggins, Dean E.

    2012-01-01

    Black-tailed prairie dogs (Cynomys ludovicianus) can surface-plug openings to a burrow occupied by a black-footed ferret (Mustela nigripes). At a coarse scale, surface plugs are more common in colonies of prairie dogs occupied by ferrets than in colonies without ferrets. However, little is known about spatial and temporal patterns of surface plugging in a colony occupied by ferrets. In a 452-ha colony of black-tailed prairie dogs in South Dakota, we sampled burrow openings for surface plugs and related those data to locations of ferrets observed during spotlight surveys. Of 67,574 burrow openings in the colony between June and September 2007, 3.7% were plugged. In a colony-wide grid of 80 m x 80 m cells, the occurrence of surface plugging (≤1 opening plugged) was greater in cells used by ferrets (93.3% of cells) than in cells not observably used by ferrets (70.6%). Rates of surface plugging (percentages of openings plugged) were significantly higher in cells used by ferrets (median = 3.7%) than in cells without known ferret use (median = 3.2%). Also, numbers of ferret locations in cells correlated positively with numbers of mapped surface plugs in the cells. To investigate surface plugging at finer temporal and spatial scales, we compared rates of surface plugging in 20-m-radius circle-plots centered on ferret locations and in random plots 1–4 days after observing a ferret (Jun–Oct 2007 and 2008). Rates of surface plugging were greater in ferret-plots (median = 12.0%) than in random plots (median = 0%). For prairie dogs and their associates, the implications of surface plugging could be numerous. For instance, ferrets must dig to exit or enter plugged burrows (suggesting energetic costs), and surface plugs might influence microclimates in burrows and consequently influence species that cannot excavate soil (e.g., fleas that transmit the plague bacterium Yersinia pestis).

  11. Patterns of surface burrow plugging in a colony of black-tailed prairie dogs occupied by black-footed ferrets

    USGS Publications Warehouse

    Eads, D.A.; Biggins, D.E.

    2012-01-01

    Black-tailed prairie dogs (Cynomys ludovicianus) can surface-plug openings to a burrow occupied by a black-footed ferret (Mustela nigripes). At a coarse scale, surface plugs are more common in colonies of prairie dogs occupied by ferrets than in colonies without ferrets. However, little is known about spatial and temporal patterns of surface plugging in a colony occupied by ferrets. In a 452-ha colony of black-tailed prairie dogs in South Dakota, we sampled burrow openings for surface plugs and related those data to locations of ferrets observed during spotlight surveys. Of 67,574 burrow openings in the colony between June and September 2007, 3.7% were plugged. In a colony-wide grid of 80 m × 80 m cells, the occurrence of surface plugging (≥1 opening plugged) was greater in cells used by ferrets (93.3% of cells) than in cells not observably used by ferrets (70.6%). Rates of surface plugging (percentages of openings plugged) were significantly higher in cells used by ferrets (median = 3.7%) than in cells without known ferret use (median = 3.2%). Also, numbers of ferret locations in cells correlated positively with numbers of mapped surface plugs in the cells. To investigate surface plugging at finer temporal and spatial scales, we compared rates of surface plugging in 20-m-radius circle-plots centered on ferret locations and in random plots 1–4 days after observing a ferret (Jun–Oct 2007 and 2008). Rates of surface plugging were greater in ferret-plots (median = 12.0%) than in random plots (median = 0%). For prairie dogs and their associates, the implications of surface plugging could be numerous. For instance, ferrets must dig to exit or enter plugged burrows (suggesting energetic costs), and surface plugs might influence microclimates in burrows and consequently influence species that cannot excavate soil (e.g., fleas that transmit the plague bacterium Yersinia pests).

  12. Novel calicivirus from a ferret badger (Melogale moschata) in China.

    PubMed

    Miao, Fa-Ming; Li, Yue-Hong; Liu, Ye; Zhang, Shou-Feng; Miao, Fu-Chun; Zhao, Jing-Hui; Hu, Rong-Liang

    2015-07-01

    We describe the isolation and complete genome sequence of a new calicivirus, FBCV-JX12, isolated from a ferret badger (Melogale moschata). Comparison of FBCV-JX12 with other vesiviruses revealed that it shared the highest amino acid sequence identities of 71.6, 60.5, and 59.3% in the nonstructural protein, VP1, and VP2, respectively, with MCV-DL2007 (mink calicivirus). Phylogenetic analysis of the whole genomic sequence showed that it clustered most closely with MCV-DL2007 of the genus Vesivirus, but with low nucleotide similarity in the three open reading frames (62.1-68.5%). PMID:25976558

  13. The host range of chronic wasting disease is altered on passage in ferrets.

    PubMed

    Bartz, J C; Marsh, R F; McKenzie, D I; Aiken, J M

    1998-11-25

    Chronic wasting disease (CWD), a member of the transmissible spongiform encephalopathies (TSEs), was first identified in captive mule and black-tail deer in 1967. Due to the failure to transmit CWD to rodents, we investigated the use of ferrets (Mustela putorius furo) as a small animal model of CWD. The inoculation of CWD into ferrets resulted in an incubation period of 17-21 months on primary passage that shortened to 5 months by the third ferret passage. The brain tissue of animals inoculated with ferret-passaged CWD exhibited spongiform degeneration and reactive astrocytosis. Western blot analysis of ferret-passaged CWD demonstrated the presence of PrP-res. Unlike mule deer CWD, ferret-passaged CWD was transmissible to Syrian golden hamsters (Mesocricetus auratus). Increasing the passage number of CWD in ferrets increased the pathogenicity of the agent for hamsters. This increase in host range of a field isolate on interspecies transmission emphasizes the need for caution when assessing the potential risk of transmission of TSEs, such as bovine spongiform encephalopathy, to new host species.

  14. Mortality of Siberian polecats and black-footed ferrets released onto prairie dog colonies

    USGS Publications Warehouse

    Biggins, D.E.; Miller, B.J.; Hanebury, L.R.; Powell, R.A.

    2011-01-01

    Black-footed ferrets (Mustela nigripes) likely were extirpated from the wild in 19851986, and their repatriation depends on captive breeding and reintroduction. Postrelease survival of animals can be affected by behavioral changes induced by captivity. We released neutered Siberian polecats (M. eversmanii), close relatives of ferrets, in 19891990 on black-tailed prairie dog (Cynomys ludovicianus) colonies in Colorado and Wyoming initially to test rearing and reintroduction techniques. Captive-born polecats were reared in cages or cages plus outdoor pens, released from elevated cages or into burrows, and supplementally fed or not fed. We also translocated wild-born polecats from China in 1990 and released captive-born, cage-reared black-footed ferrets in 1991, the 1st such reintroduction of black-footed ferrets. We documented mortality for 55 of 92 radiotagged animals in these studies, mostly due to predation (46 cases). Coyotes (Canis latrans) killed 31 ferrets and polecats. Supplementally fed polecats survived longer than nonprovisioned polecats. With a model based on deaths per distance moved, survival was highest for wild-born polecats, followed by pen-experienced, then cage-reared groups. Indexes of abundance (from spotlight surveys) for several predators were correlated with mortality rates of polecats and ferrets due to those predators. Released black-footed ferrets had lower survival rates than their ancestral population in Wyoming, and lower survival than wild-born and translocated polecats, emphasizing the influence of captivity. Captive-born polecats lost body mass more rapidly postrelease than did captive-born ferrets. Differences in hunting efficiency and prey selection provide further evidence that these polecats and ferrets are not ecological equivalents in the strict sense. ?? 2011 American Society of Mammalogists.

  15. High doses of highly pathogenic avian influenza virus in chicken meat are required to infect ferrets

    PubMed Central

    2014-01-01

    High pathogenicity avian influenza viruses (HPAIV) have caused fatal infections in mammals through consumption of infected bird carcasses or meat, but scarce information exists on the dose of virus required and the diversity of HPAIV subtypes involved. Ferrets were exposed to different HPAIV (H5 and H7 subtypes) through consumption of infected chicken meat. The dose of virus needed to infect ferrets through consumption was much higher than via respiratory exposure and varied with the virus strain. In addition, H5N1 HPAIV produced higher titers in the meat of infected chickens and more easily infected ferrets than the H7N3 or H7N7 HPAIV. PMID:24894438

  16. Variable effects of soman on macromolecular secretion by ferret trachea

    SciTech Connect

    McBride, R.K.; Zwierzynski, D.J.; Stone, K.K.; Culp, D.J.; Marin, M.G. )

    1991-01-01

    The purpose of this study was to examine the effect of the anticholinesterase agent, soman, on macromolecular secretion by ferret trachea, in vitro. We mounted pieces of ferret trachea in Ussing-type chambers. Secreted sulfated macromolecules were radiolabeled by adding 500 microCi of {sup 35}SO{sub 4} to the submucosal medium and incubating for 17 hr. Soman added to the submucosal side produced a concentration-dependent increase in radiolabeled macromolecular release with a maximal secretory response (mean +/- SD) of 202 +/- 125% (n = 8) relative to the basal secretion rate at a concentration of 10{sup {minus} 7} M. The addition of either 10{sup {minus}6} M pralidoxime (acetylcholinesterase reactivator) or 10{sup {minus}6} M atropine blocked the response to 10{sup {minus}7} M soman. At soman concentrations greater than 10{sup {minus}7} M, secretion rate decreased and was not significantly different from basal secretion. Additional experiments utilizing acetylcholine and the acetylcholinesterase inhibitor, physostigmine, suggest that inhibition of secretion by high concentrations of soman may be due to a secondary antagonistic effect of soman on muscarinic receptors.

  17. Expression of sfrp1 and activation of the Wnt pathway in the adrenal glands of healthy ferrets and neutered ferrets with hyperadrenocorticism.

    PubMed

    de Jong, Marja K; Schoemaker, Nico J; Mol, Jan A

    2013-05-01

    Gonadectomy induces the pathogenesis of luteinising hormone receptor positive, androgen and oestrogen producing tumours in the adrenal cortex of ferrets. In mice, the castration-dependent appearance of adrenocortical tumours has been attributed to loss of expression of the tumour suppressor gene Secreted Frizzled Related Protein 1 (sfrp1), a dominant inhibitor of the Wnt pathway, which controls cell proliferation and 'cell faith' decisions. This study investigated whether sfrp1 and the Wnt pathway play a similar role in the pathogenesis of hyperadrenocorticism in ferrets. The expression of sfrp1 and three target genes of the Wnt pathway (c-myc, axin2 and cyclinD1) in seven adrenal glands from healthy ferrets and in 13 adrenocortical tumours were studied by quantitative real-time PCR. Nuclear β-catenin staining was assessed by immunohistochemistry. Sfrp1 mRNA expression was up-regulated and axin2 and cyclinD1 were down-regulated in the tumour group in comparison with the control group. Decreased nuclear β-catenin staining supported the decrease in active Wnt signalling in adrenocortical tumours in ferrets. Therefore, it is unlikely that the involvement of sfrp1 and the Wnt pathway in the pathogenesis of adrenocortical tumours in ferrets is similar to that described in mice.

  18. Pathogenesis of novel reassortant avian influenza virus A (H5N8) Isolates in the ferret.

    PubMed

    Kim, Heui Man; Kim, Chi-Kyeong; Lee, Nam-Joo; Chu, Hyuk; Kang, Chun; Kim, Kisoon; Lee, Joo-Yeon

    2015-07-01

    Outbreaks of avian influenza virus H5N8 first occurred in 2014, and spread to poultry farms in Korea. Although there was no report of human infection by this subtype, it has the potential to threaten human public health. Therefore, we evaluated the pathogenesis of H5N8 viruses in ferrets. Two representative Korean H5N8 strains did not induce mortality and significant respiratory signs after an intranasal challenge in ferrets. However, ferrets intratracheally infected with A/broiler duck/Korea/Buan2/2014 virus showed dose-dependent mortality. Although the Korean H5N8 strains were classified as the HPAI virus, possessing multiple basic amino acids in the cleavage site of the hemagglutinin sequence, they did not produce pathogenesis in ferrets challenged intranasally, similar to the natural infection route. These results could be useful for public health by providing the pathogenic characterization of H5N8 viruses. PMID:25776760

  19. Eradication of Helicobacter mustelae from the ferret stomach: an animal model of Helicobacter (Campylobacter) pylori chemotherapy.

    PubMed Central

    Otto, G; Fox, J G; Wu, P Y; Taylor, N S

    1990-01-01

    Colonization of the ferret stomach by Helicobacter mustelae has been suggested as a possible animal model for Helicobacter pylori-associated gastroduodenal disease of humans. Our study was designed to determine whether antimicrobial chemotherapy could eradicate H. mustelae from ferrets. Triple antimicrobial therapy combining amoxicillin, metronidazole, and bismuth subsalicylate was successful in eradicating the organism from 5 of 7 (71%) adult ferrets. Despite apparent in vitro susceptibility, neither chloramphenicol monotherapy nor a polytherapeutic regimen combining tetracycline, metronidazole, and bismuth subsalicylate proved effective in the eradication of H. mustelae. Several strains isolated after unsuccessful polytherapy showed markedly increased resistance to metronidazole. These preliminary findings are similar to results of H. pylori treatment trials with humans and suggest that the ferret may be a useful model for evaluating and comparing potential antimicrobial modalities for the eradication of H. pylori. PMID:2393285

  20. Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model▿

    PubMed Central

    Yen, Hui-Ling; Lipatov, Aleksandr S.; Ilyushina, Natalia A.; Govorkova, Elena A.; Franks, John; Yilmaz, Neziha; Douglas, Alan; Hay, Alan; Krauss, Scott; Rehg, Jerold E.; Hoffmann, Erich; Webster, Robert G.

    2007-01-01

    The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synthetic sialosaccharides with α2,3 or α2,6 linkages) on transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess “avian-like” α2,3-linked sialic acid (SA) receptor specificity, caused neurological symptoms and death in ferrets inoculated with 103 50% tissue culture infectious doses. A/Hong Kong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for “human-like” α2,6-linked SA receptors in addition to their affinity for α2,3-linked SA receptors, caused mild clinical symptoms and were not lethal to the ferrets. No transmission of A/Vietnam/1203/04 or A/Turkey/65-596/06 virus was detected. One contact ferret developed neutralizing antibodies to A/Hong Kong/213/03 but did not exhibit any clinical signs or detectable virus shedding. In two groups, one of two naïve contact ferrets had detectable virus after 6 to 8 days when housed together with the A/Vietnam/JP36-2/05 virus-inoculated ferrets. Infected contact ferrets showed severe clinical signs, although little or no virus was detected in nasal washes. This limited virus shedding explained the absence of secondary transmission from the infected contact ferret to the other naïve ferret that were housed together. Our results suggest that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammalian species. PMID:17459930

  1. Rostral maxillectomy and radiation therapy to manage squamous cell carcinoma in a ferret.

    PubMed

    Graham, Jennifer; Fidel, Janean; Mison, Michael

    2006-09-01

    A 4-year-old, male, neutered ferret presented with squamous cell carcinoma of the right maxillary region associated with the tissues surrounding the upper canine tooth. A rostral maxillectomy was performed to excise the mass. Histopathologic examination showed questionable margins of tumor removal. Approximately 2 months after surgery, the ferret received a course of radiation therapy and is currently being monitored for tumor regrowth.

  2. Jaundice and bilirubinemia as manifestations of canine distemper in raccoons and ferrets

    USGS Publications Warehouse

    Kilham, L.; Habermann, R.T.; Herman, C.M.

    1956-01-01

    1) Two strains of distemper virus have been isolated from wild raccoons and one strain from ferrets. 2) All strains isolated have induced bilirubinemia in raccoons and ferrets. Many raccoons with bilirubinemia also had jaundice. 3) Identification of these strains as members of the canine distemper virus complex has been by clinical and pathological findings consistent with this diagnosis as well as by cross-immunity tests.

  3. Comparative Processing and Function of Human and Ferret Cystic Fibrosis Transmembrane Conductance Regulator*

    PubMed Central

    Fisher, John T.; Liu, Xiaoming; Yan, Ziying; Luo, Meihui; Zhang, Yulong; Zhou, Weihong; Lee, Ben J.; Song, Yi; Guo, Chenhong; Wang, Yujiong; Lukacs, Gergely L.; Engelhardt, John F.

    2012-01-01

    The most common cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation is ΔF508, and this causes cystic fibrosis (CF). New CF models in the pig and ferret have been generated that develop lung, pancreatic, liver, and intestinal pathologies that reflect disease in CF patients. Species-specific biology in the processing of CFTR has demonstrated that pig and mouse ΔF508-CFTR proteins are more effectively processed to the apical membrane of airway epithelia than human ΔF508-CFTR. The processing behavior of ferret WT- and ΔF508-CFTR proteins remains unknown, and such information is important to predicting the utility of a ΔF508-CFTR ferret. To this end, we sought to compare processing, membrane stability, and function of human and ferret WT- and ΔF508-CFTR proteins in a heterologous expression system using HT1080, HEK293T, BHK21, and Cos7 cells as well as human and ferret CF polarized airway epithelia. Analysis of the protein processing and stability by metabolic pulse-chase and surface On-Cell Western blots revealed that WT-fCFTR half-life and membrane stability were increased relative to WT-hCFTR. Furthermore, in BHK21, Cos7, and CuFi cells, human and ferret ΔF508-CFTR processing was negligible, whereas low levels of processing of ΔF508-fCFTR could be seen in HT1080 and HEK293T cells. Only the WT-fCFTR, but not ΔF508-fCFTR, produced functional cAMP-inducible chloride currents in both CF human and ferret airway epithelia. Further elucidation of the mechanism responsible for elevated fCFTR protein stability may lead to new therapeutic approaches to augment CFTR function. These findings also suggest that generation of a ferret CFTRΔF508/ΔF508 animal model may be useful. PMID:22570484

  4. Sodium-dependent magnesium uptake by ferret red cells.

    PubMed Central

    Flatman, P W; Smith, L M

    1991-01-01

    1. Magnesium uptake can be measured in ferret red cells incubated in media containing more than 1 mM-magnesium. Uptake is substantially increased if the sodium concentration in the medium is reduced. 2. Magnesium uptake is half-maximally activated by 0.37 mM-external magnesium when the external sodium concentration is 5 mM. Increasing the external sodium concentration increases the magnesium concentration needed to activate the system. 3. Magnesium uptake is increased by reducing the external sodium concentration. Uptake is half-maximum at sodium concentrations of 17, 22 and 62 nM when the external magnesium concentrations are 2, 5 and 10 mM respectively. 4. Replacement of external sodium with choline does not affect the membrane potential of ferret red cells over a 45 min period. 5. Magnesium uptake from media containing 5 mM-sodium is inhibited by amiloride, quinidine and imipramine. It is not affected by ouabain or bumetanide. Vanadate stimulates magnesium uptake but has no effect on magnesium efflux. 6. When cell ATP content is reduced to 19 mumol (1 cell)-1 by incubating cells for 3 h with 2-deoxyglucose, magnesium uptake falls by 50% in the presence of 5 mM-sodium and is completely abolished in the presence of 145 mM-sodium. Some of the inhibition may be due to the increase in intracellular ionized magnesium concentration ([Mg2+]i) from 0.7 to 1.0 mM which occurs under these conditions. 7. Magnesium uptake can be driven against a substantial electrochemical gradient if the external sodium concentration is reduced sufficiently. 8. These findings are discussed in terms of several possible models for magnesium transport. It is concluded that the majority of magnesium uptake observed in low-sodium media is via sodium-magnesium antiport. A small portion of uptake is through a parallel leak pathway. It is believed that the antiport is responsible for maintaining [Mg2+]i below electrochemical equilibrium in these cells at physiological external sodium concentration

  5. Protecting Black-Footed Ferrets and Prairie Dogs Against Sylvatic Plague

    USGS Publications Warehouse

    Rocke, Tonie E.

    2008-01-01

    Scientists at the USGS National Wildlife Health Center (NWHC), in collaboration with colleagues at other federal agencies and the University of Wisconsin, are developing and testing vaccines that can be used to protect black-footed ferrets and prairie dogs against plague. The black-footed ferret is commonly regarded as the most endangered mammal in North America, and sylvatic plague is a major impediment to its recovery. The three prairie dog species (Gunnison's, black-tailed, and white-tailed prairie dogs), upon which the ferret depends for food and whose burrows they use for shelter, have been drastically reduced from historical levels, resulting in the near extinction of the ferret. All three species are considered 'at risk' and have been petitioned for listing as 'threatened' or 'endangered' by the U.S. Fish and Wildlife Service (FWS). Additionally, the Utah prairie dog is listed as threatened and the Mexican prairie dog is considered endangered in Mexico. Like the black-footed ferret, all five prairie dog species are highly susceptible to plague and regularly experience outbreaks with devastating losses. Controlling plague outbreaks in prairie dogs and ferrets is a vital concern for ongoing recovery programs and conservation efforts for both species.

  6. Diabetes mellitus in a black-footed ferret

    USGS Publications Warehouse

    Carpenter, J.W.; Novilla, M.N.

    1977-01-01

    Diabetes mellitus was tentatively diagnosed in a black-footed ferret with polyuria, polydipsia, polyphagia, dehydration, and weight loss. Laboratory findings (marked hyperglycemia (724 mg/100 ml), glycosuria, and ketonuria) and the subsequent favorable response to insulin therapy confirmed the diagnosis. Although lesions were not observed in the pancreas, gross and histologic findings concomitant with diabetes mellitus included arteriosclerosis, with calcification of the aorta and other major vessels; mild necrotizing hepatitis; and mild proliferative glomerulonephritis. A perineal adenocarcinoma, with metastasis to an internal iliac lymph node, was an incidental finding. Special stains demonstrated adequate numbers of beta cell granules in the islets of Langerhans. Thus, the diabetes was apparently due to a lack of release of the synthesized insulin or to diminished effectiveness of the secreted insulin.

  7. Activity of radio-tagged black-footed ferrets

    USGS Publications Warehouse

    Biggins, Dean E.; Shroeder, Max H.; Forrest, Steven C.; Richardson, Louise

    1986-01-01

    Activity of two radio-tagged black-footed ferrets (Mustela nigripes) was investigated during October-November 1981 (an adult male monitored for 16 days), and during August-November 1982 (a young female monitored for 101 days). Aboveground activity of the male averaged 2.95 hr/night, 15% of the total time monitored. From 22 September to 5 November, aboveground activity of the female averaged 1.9 hours; 26% of the time she was stationary and 74% of the time she was moving. During August the juvenile female emerged at least once on 93% of the nights. She was least active in November. Both animals were primarily nocturnal (although daylight activity was not uncommon), and timing of nightly activity was similar, peaking from 0100 to 0359.

  8. Histochemical and immunohistochemical characterization of chordoma in ferrets

    PubMed Central

    YUI, Takeshi; OHMACHI, Tetsuo; MATSUDA, Kazuya; OKAMOTO, Minoru; TANIYAMA, Hiroyuki

    2015-01-01

    Chordomas of the tip of the tail in 6 ferrets were examined using histopathological, histochemical and immunohistochemical procedures. Histopathologically, round neoplastic cells containing numerous cytoplasmic vacuoles of varying sizes, categorized as “physaliphorous cells”, were observed in the amorphous eosinophilic or pale basophilic myxoid stroma. Physaliphorous cells were arranged in lobules and in a “chordoid” or “cobblestone” manner. The neoplasms were diagnosed as benign chordoma without local invasion and metastasis. Histochemically, the cytoplasm of small neoplastic cells was positive for periodic acid-Schiff stain and alcian blue (AB) pH 2.5 and pH 1.0 stains, but negative for hyaluronidase digestion-AB pH 2.5 stain. All neoplastic cells were strongly stained with colloidal ion, negative for high iron diamine AB pH 2.5 and toluidine blue pH 2.5 stains, and positive for Mayer’s mucicarmine stain. Immunohistochemistry using antibodies directed against low-molecular-weight cytokeratins (CK18, CK19 and CK20), vimentin and mucin core protein (MUC5AC) revealed that neoplastic cells had both epithelial and mesenchymal elements. The expression of low-molecular-weight cytokeratins suggests that neoplastic cells acquired the properties of glandular epithelial cells and produced epithelial mucus. Furthermore, the expression of cytokeratins, vimentin, S100 protein, brachyury and epithelial membrane antigen indicates that the neoplasms were equivalent to the classic type of human chordoma. Therefore, immunohistochemistry using these antibodies can be useful for the characterization of ferret chordoma. PMID:25648567

  9. Initiation of teeth from the dental lamina in the ferret.

    PubMed

    Jussila, Maria; Crespo Yanez, Xenia; Thesleff, Irma

    2014-01-01

    Mammalian tooth development is characterized by formation of primary teeth that belong to different tooth classes and are later replaced by a single set of permanent teeth. The first primary teeth are initiated from the primary dental lamina, and the replacement teeth from the successional dental lamina at the lingual side of the primary teeth. An interdental lamina connects the primary tooth germs together. Most mammalian tooth development research is done on mouse, which does not have teeth in all tooth classes, does not replace its teeth, and does not develop an interdental lamina. We have used the ferret (Mustela putorius furo) as a model animal to elucidate the morphological changes and gene expression during the development of the interdental lamina and the initiation of primary teeth. In addition we have analyzed cell-cell signaling taking place in the interdental lamina as well as in the successional lamina during tooth replacement. By 3D reconstructions of serial histological sections we observed that the morphogenesis of the interdental lamina and the primary teeth are intimately linked. Expression of Pitx2 and Foxi3 in the interdental lamina indicates that it has odontogenic identity, and there is active signaling taking place in the interdental lamina. Bmp4 is coexpressed with the stem cell factor Sox2 at its lingual aspect suggesting that the interdental lamina may retain competence for tooth initiation. We show that when tooth replacement is initiated there is Wnt pathway activity in the budding successional lamina and adjacent mesenchyme but no active Fgf or Eda signaling. Genes associated with human tooth replacement phenotypes, including Runx2 and Il11rα, are mostly expressed in the mesenchyme around the successional lamina in the ferret. Our results highlight the importance of the dental lamina in the mammalian tooth development during the initiation of both primary and replacement teeth.

  10. Resource selection models are useful in predicting fine-scale distributions of black-footed ferrets in prairie dog colonies

    USGS Publications Warehouse

    Eads, David A.; Jachowski, David S.; Biggins, Dean E.; Livieri, Travis M.; Matchett, Marc R.; Millspaugh, Joshua J.

    2012-01-01

    Wildlife-habitat relationships are often conceptualized as resource selection functions (RSFs)—models increasingly used to estimate species distributions and prioritize habitat conservation. We evaluated the predictive capabilities of 2 black-footed ferret (Mustela nigripes) RSFs developed on a 452-ha colony of black-tailed prairie dogs (Cynomys ludovicianus) in the Conata Basin, South Dakota. We used the RSFs to project the relative probability of occurrence of ferrets throughout an adjacent 227-ha colony. We evaluated performance of the RSFs using ferret space use data collected via postbreeding spotlight surveys June–October 2005–2006. In home ranges and core areas, ferrets selected the predicted "very high" and "high" occurrence categories of both RSFs. Count metrics also suggested selection of these categories; for each model in each year, approximately 81% of ferret locations occurred in areas of very high or high predicted occurrence. These results suggest usefulness of the RSFs in estimating the distribution of ferrets throughout a black-tailed prairie dog colony. The RSFs provide a fine-scale habitat assessment for ferrets that can be used to prioritize releases of ferrets and habitat restoration for prairie dogs and ferrets. A method to quickly inventory the distribution of prairie dog burrow openings would greatly facilitate application of the RSFs.

  11. Enzootic plague reduces black-footed ferret (Mustela nigripes) survival in Montana

    USGS Publications Warehouse

    Matchett, Marc R.; Biggins, Dean E.; Carlson, Valerie; Powell, Bradford; Rocke, Tonie E.

    2010-01-01

    Black-footed ferrets (Mustela nigripes) require extensive prairie dog colonies (Cynomys spp.) to provide habitat and prey. Epizootic plague kills both prairie dogs and ferrets and is a major factor limiting recovery of the highly endangered ferret. In addition to epizootics, we hypothesized that enzootic plague, that is, presence of disease-causing Yersinia pestis without any noticeable prairie dog die off, may also affect ferret survival. We reduced risk of plague on portions of two ferret reintroduction areas by conducting flea control for 3 years. Beginning in 2004, about half of the ferrets residing on dusted and nondusted colonies were vaccinated against plague with an experimental vaccine (F1-V fusion protein). We evaluated 6-month reencounter rates (percentage of animals observed at the end of an interval that were known alive at the beginning of the interval), an index to survival, for ferrets in four treatment groups involving all combinations of vaccination and flea control. For captive-reared ferrets (115 individuals observed across 156 time intervals), reencounter rates were higher for vaccinates (0.44) than for nonvaccinates (0.23, p = 0.044) on colonies without flea control, but vaccination had no detectable effect on colonies with flea control (vaccinates = 0.41, nonvaccinates = 0.42, p = 0.754). Flea control resulted in higher reencounter rates for nonvaccinates (p = 0.026), but not for vaccinates (p = 0.508). The enhancement of survival due to vaccination or flea control supports the hypothesis that enzootic plague reduces ferret survival, even when there was no noticeable decline in prairie dog abundance. The collective effects of vaccination and flea control compel a conclusion that fleas are required for maintenance, and probably transmission, of plague at enzootic levels. Other studies have demonstrated similar effects of flea control on several species of prairie dogs and, when combined with this study, suggest

  12. Defective innate immunity and hyperinflammation in newborn cystic fibrosis transmembrane conductance regulator-knockout ferret lungs.

    PubMed

    Keiser, Nicholas W; Birket, Susan E; Evans, Idil A; Tyler, Scott R; Crooke, Adrianne K; Sun, Xingshen; Zhou, Weihong; Nellis, Joseph R; Stroebele, Elizabeth K; Chu, Kengyeh K; Tearney, Guillermo J; Stevens, Mark J; Harris, J Kirk; Rowe, Steven M; Engelhardt, John F

    2015-06-01

    Mucociliary clearance (MCC) and submucosal glands are major components of airway innate immunity that have impaired function in cystic fibrosis (CF). Although both of these defense systems develop postnatally in the ferret, the lungs of newborn ferrets remain sterile in the presence of a functioning cystic fibrosis transmembrane conductance regulator gene. We evaluated several components of airway innate immunity and inflammation in the early CF ferret lung. At birth, the rates of MCC did not differ between CF and non-CF animals, but the height of the airway surface liquid was significantly reduced in CF newborn ferrets. CF ferrets had impaired MCC after 7 days of age, despite normal rates of ciliogenesis. Only non-CF ferrets eradicated Pseudomonas directly introduced into the lung after birth, whereas both genotypes could eradicate Staphylococcus. CF bronchoalveolar lavage fluid (BALF) had significantly lower antimicrobial activity selectively against Pseudomonas than non-CF BALF, which was insensitive to changes in pH and bicarbonate. Liquid chromatography-tandem mass spectrometry and cytokine analysis of BALF from sterile Caesarean-sectioned and nonsterile naturally born animals demonstrated CF-associated disturbances in IL-8, TNF-α, and IL-β, and pathways that control immunity and inflammation, including the complement system, macrophage functions, mammalian target of rapamycin signaling, and eukaryotic initiation factor 2 signaling. Interestingly, during the birth transition, IL-8 was selectively induced in CF BALF, despite no genotypic difference in bacterial load shortly after birth. These results suggest that newborn CF ferrets have defects in both innate immunity and inflammatory signaling that may be important in the early onset and progression of lung disease in these animals.

  13. Assessment of a blood preservation protocol for use in ferrets before transfusion.

    PubMed

    Pignon, C; Donnelly, T M; Todeschini, C; Deschamps, J Y; Roux, F A

    2014-03-15

    Blood transfusion has been described in ferrets as a treatment for oestrus-associated anaemia and as a life-saving therapy following trauma, iatrogenic (usually surgery-induced) anaemia, autoimmune haemolytic anaemia and pure red cell aplasia. Although blood banking is a common method for storage of feline and canine blood it is not currently done with ferret blood. The aim of this study was to determine the shelf-life of ferret blood using the anticoagulant citrate-phosphate-dextrose-solution with adenine (CPDA). Two male ferrets were used as blood donors. From each ferret, 6 ml of blood was taken from the cranial vena cava and stored in 10 ml polyethylene terephthalate (PET) blood tubes containing 1 ml of CPDA solution. Blood was taken from each ferret once per month for five months. These 10 blood samples were stored in a laboratory refrigerator at 4°C for four weeks. Biochemical (glucose, pH, lactate, potassium, sodium) and haematological (haematocrit, light microscopic blood smear examination) analyses were performed on the stored blood at days 0, 7, 14, 21 and 28. Biochemical analyses revealed a progressive decrease from day seven in the stored blood pH, glucose and sodium, with a concomitant increase in lactate and potassium. These results are attributable to the ongoing metabolism and deterioration of the red blood cells (RBC) while in storage, and are more rapid than described for human or canine stored blood. Haematological analyses revealed a progressive elevation of the haematocrit due to the appearance of hypochromic red blood cells and echinocytes beginning at day 7. Haemolysis was observed in the microhaematocrit capillary tube sample by day 21, and microscopic clots were visible on the blood smear by day 28. The low blood pH and the appearance of many hypochromic RBCs and some echinocytes from day 7 in CPDA-stored ferret blood, suggest stored ferret blood has a short shelf-life when compared with stored human or canine blood. We recommend that

  14. Environmental enrichment affects adrenocortical stress responses in the endangered black-footed ferret.

    PubMed

    Poessel, Sharon A; Biggins, Dean E; Santymire, Rachel M; Livieri, Travis M; Crooks, Kevin R; Angeloni, Lisa

    2011-07-01

    Potential stressors of wildlife living in captivity, such as artificial living conditions and frequent human contact, may lead to a higher occurrence of disease and reduced reproductive function. One successful method used by wildlife managers to improve general well-being is the provision of environmental enrichment, which is the practice of providing animals under managed care with environmental stimuli. The black-footed ferret (Mustela nigripes) is a highly-endangered carnivore species that was rescued from extinction by removal of the last remaining individuals from the wild to begin an ex situ breeding program. Our goal was to examine the effect of environmental enrichment on adrenocortical activity in ferrets by monitoring fecal glucocorticoid metabolites (FGM). Results demonstrated that enrichment lowered FGM in juvenile male ferrets, while increasing it in adult females; enrichment had no effect on FGM in juvenile females and adult males. These results correspond with our findings that juvenile males interacted more with the enrichment items than did adult females. However, we did not detect an impact of FGM on the incidence of disease or on the ability of ferrets to become reproductive during the following breeding season. We conclude that an environmental enrichment program could benefit captive juvenile male ferrets by reducing adrenocortical activity.

  15. Influence of prerelease experience on reintroduced black-footed ferrets (Mustela nigripes)

    USGS Publications Warehouse

    Biggins, D.E.; Vargas, A.; Godbey, J.L.; Anderson, S.H.

    1999-01-01

    Captive breeding is increasingly being used to create supplies of endangered animals for release into natural habitats, but rearing strategies vary and debates arise over which methods are most efficient. We assessed postrelease behaviors and survival of three groups of black-footed ferrets, each with different prerelease experience. Eighteen ferret kits ???60 days of age were moved with their dams from cages to 80-m2 outdoor pens with prairie dog burrows. These animals were compared to animals reared in standard cages (n = 72), some of which were given experience killing prairie dogs (n = 32). Ferrets were released onto white-tailed prairie dog (Cynomys leucurus) colonies in Wyoming, USA, in fall, 1992. Radio-tagged cage-reared ferrets made longer nightly moves and dispersed further from release sites than their pen-reared counterparts. The band return rate was 4-fold higher for pen-reared animals than for cage-reared animals during surveys conducted about 1 month after release. We recommend routine use of quasi-natural outdoor pens for prerelease conditioning of black-footed ferrets.

  16. Environmental enrichment affects adrenocortical stress responses in the endangered black-footed ferret

    USGS Publications Warehouse

    Poessel, S.A.; Biggins, D.E.; Santymire, R.M.; Livieri, T.M.; Crooks, K.R.; Angeloni, L.

    2011-01-01

    Potential stressors of wildlife living in captivity, such as artificial living conditions and frequent human contact, may lead to a higher occurrence of disease and reduced reproductive function. One successful method used by wildlife managers to improve general well-being is the provision of environmental enrichment, which is the practice of providing animals under managed care with environmental stimuli. The black-footed ferret (Mustela nigripes) is a highly-endangered carnivore species that was rescued from extinction by removal of the last remaining individuals from the wild to begin an ex situ breeding program. Our goal was to examine the effect of environmental enrichment on adrenocortical activity in ferrets by monitoring fecal glucocorticoid metabolites (FGM). Results demonstrated that enrichment lowered FGM in juvenile male ferrets, while increasing it in adult females; enrichment had no effect on FGM in juvenile females and adult males. These results correspond with our findings that juvenile males interacted more with the enrichment items than did adult females. However, we did not detect an impact of FGM on the incidence of disease or on the ability of ferrets to become reproductive during the following breeding season. We conclude that an environmental enrichment program could benefit captive juvenile male ferrets by reducing adrenocortical activity. ?? 2011 Elsevier Inc.

  17. A comparison of epigean and subterranean locomotion in the domestic ferret (Mustela putorius furo: Mustelidae: Carnivora).

    PubMed

    Horner, Angela M; Biknevicius, Audrone R

    2010-05-01

    Burrows are used by many mammals to escape predation, cache food and for parturition. Although the construction of burrows has been studied in some taxa, the locomotion while inside of them has received scant attention. In this study we collected simultaneous video and force data to characterize gaits, kinematics, peak ground reaction forces (GRFs) and external mechanical energy profiles in the domestic ferret, an animal that displays the typical morphology and behaviors associated with subterranean adaptations in mustelines. We compared kinematics and kinetics between locomotion in two experimental conditions: subterranean, simulated by a Plexiglass tunnel designed such that the ferrets' peak back height was reduced by 40% and hip height by 25%, and epigean, or unconstrained overground. Despite the large change in posture, a striking number of gait and force variables were not statistically different between experimental conditions. In both subterranean and epigean conditions, the ferrets in our study traveled at similar average velocities (approximately 0.8 m s(-1)), preferred to use a lateral-sequence diagonal-couplet gait, and were more likely to demonstrate the in-phase fluctuations of external mechanical energy indicative of running mechanics (68% of all trials). The ferrets conformed to gait and mechanical patterns seen in a variety of other small (<1 kg) mammals rather than being unique, despite the divergent morphology of mustelines. Our results demonstrated biodynamically similar locomotion in both epigean and subterranean conditions and support the hypothesis that ferrets possess adaptations for tunnel locomotion. PMID:20545058

  18. Genetic diversity and fitness in black-footed ferrets before and during a bottleneck.

    PubMed

    Wisely, S M; Buskirk, S W; Fleming, M A; McDonald, D B; Ostrander, E A

    2002-01-01

    The black-footed ferret (Mustela nigripes) is an endangered North American carnivore that underwent a well-documented population bottleneck in the mid-1980s. To better understand the effects of a bottleneck on a free-ranging carnivore population, we used 24 microsatellite loci to compare genetic diversity before versus during the bottleneck, and compare the last wild population to two historical populations. We also compared genetic diversity in black-footed ferrets to that of two sibling species, the steppe polecat (Mustela eversmanni) and the European polecat (Mustela putorius). Black-footed ferrets during the bottleneck had less genetic diversity than steppe polecats. The three black-footed ferret populations were well differentiated (F(ST) = 0.57 +/- 0.15; mean +/- SE). We attributed the decrease in genetic diversity in black-footed ferrets to localized extinction of these genetically distinct subpopulations and to the bottleneck in the surviving subpopulation. Although genetic diversity decreased, female fecundity and juvenile survival were not affected by the population bottleneck. PMID:12407208

  19. The effect of rearing methods on survival of reintroduced black-footed ferrets

    USGS Publications Warehouse

    Biggins, D.E.; Godbey, J.L.; Hanebury, L.R.; Luce, B.; Marinari, P.E.; Matchett, M.R.; Vargas, A.

    1998-01-01

    We estimated minimum survival rates for 282 young-of-year, captive-reared, black-footed ferrets (Mustela nigripes) reintroduced into prairie dog (Cynomys spp.) colonies in Wyoming, Montana, and South Dakota. We used night surveys with spotlights to locate ferrets about 1 month and 9 months postrelease. We modeled minimum survival rates using gender, year, site, and 4 rearing methods. Minimum survival rates were highest (30% for 1 month, 20% for 9 months) for ferrets reared from early ages in outdoor pens with simulated prairie dog habitat; survival was lowest for cage-reared ferrets released without pen experience (11% for 1 month, 2% for 9 months). Rearing method and year influenced 1-month survival in a comparison of 3 levels of pen experience (pen rearing as defined above, transfer of kits from zoos to pen facilities at age 60-90 days, transfer at age >90 days) during releases in 1994-95 in Montana. Higher survival was associated with intensive management of coyotes (Canis latrans) in 1995. Survival was not different (P > 0.05) between sites or sexes, regardless of model. We recommend routine use of outdoor pens for prerelease conditioning of black-footed ferret kits.

  20. Neuropeptides degranulate serous cells of ferret tracheal glands

    SciTech Connect

    Gashi, A.A.; Borson, D.B.; Finkbeiner, W.E.; Nadel, J.A.; Basbaum, C.B.

    1986-08-01

    To determine whether serous or mucous cells in tracheal submucosal glands respond to the neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP). The authors studied the peptide-induced changes in gland cell morphology accompanying release of TVSO4-labeled macromolecules from tracheal explants of ferrets. Explants were labeled for 1 h in medium containing TVSO4 and washed for 3.5 additional hours. Base-line secretion in the absence of drugs declined between 1.5 and 3.5 h after the pulse. Between 2.5 and 3.5 h, the average percent change in counts per minute recovered per sample period was not significantly different from zero. Substance P and VIP added 4 h after labeling each increased greatly the release of TVSO4-labeled macromolecules above base line. Bethanechol, a muscarinic-cholinergic agonist, increased secretion by an average of 142% above base line. Light and electron microscopy of the control tissues showed glands with narrow lumens and numerous secretory granules. Glands treated with SP or VIP had enlarged lumens and the serous cells were markedly degranulated. These phenomena were documented by morphometry and suggest that SP and VIP cause secretion from glands at least partially by stimulating exocytosis from serous cells.

  1. A test of mink microsatellite markers in the ferret: amplification and sequence comparisons.

    PubMed

    Anistoroaei, R; Christensen, K

    2006-12-01

    Short tandem repeats are a source of highly polymorphic markers in mammalian genomes. Genetic variation at these hypervariable loci is extensively used for linkage analysis and to identify individuals, and is very useful for interpopulation and interspecies studies. Fifty-nine microsatellite markers from American mink were tested in the ferret, under the same conditions as for the mink. Of the 59, 43 of them (73.5%) amplified a ferret sequence; 5 amplification products differed in size from the respective mink sequences. Ten amplified fragments from ferret were sequenced. The sequences that were identical in size to those from mink displayed a high degree of conservation, with some differences at the repeat motif sites. These results could aid cross-utilization of markers between these two species. PMID:17362355

  2. Black-footed ferret areas of activity during late summer and fall at Meeteetse, Wyoming

    USGS Publications Warehouse

    Fagerstone, K.A.; Biggins, D.E.

    2011-01-01

    Radiotelemetry was used during 1983 and 1984 to collect information on short-term areas of activity for black-footed ferrets (Mustela nigripes) near Meeteetse, Wyoming. This population ultimately provided ferrets for the captive-breeding program that bred and released offspring into the wild since 1991. We fitted 5 adult ferrets and 13 juveniles with radiotransmitters and followed their movements during late summer and fall. Adult males had 7-day areas of activity that were >6 times as large as those of adult females. Activity areas of adult males varied little in coverage or location on a weekly basis, but females sequentially shifted their areas. Unlike juvenile females, juvenile males tended to leave their natal colonies. ?? 2011 American Society of Mammalogists.

  3. Bacterial sinusitis and otitis media following influenza virus infection in ferrets.

    PubMed

    Peltola, Ville T; Boyd, Kelli L; McAuley, Julie L; Rehg, Jerold E; McCullers, Jonathan A

    2006-05-01

    Streptococcus pneumoniae is the leading cause of otitis media, sinusitis, and pneumonia. Many of these infections result from antecedent influenza virus infections. In this study we sought to determine whether the frequency and character of secondary pneumococcal infections differed depending on the strain of influenza virus that preceded bacterial challenge. In young ferrets infected with influenza virus and then challenged with pneumococcus, influenza viruses of any subtype increased bacterial colonization of the nasopharynx. Nine out of 10 ferrets infected with H3N2 subtype influenza A viruses developed either sinusitis or otitis media, while only 1 out of 11 ferrets infected with either an H1N1 influenza A virus or an influenza B virus did so. These data may partially explain why bacterial complication rates are higher during seasons when H3N2 viruses predominate. This animal model will be useful for further study of the mechanisms that underlie viral-bacterial synergism.

  4. FATAL GASTRIC DILATION IN TWO ADULT BLACK-FOOTED FERRETS (MUSTELA NIGRIPES).

    PubMed

    Hinton, Jenna D; Aitken-Palmer, Copper; Joyner, Priscilla H; Ware, Lisa; Walsh, Timothy F

    2016-03-01

    Acute gastric dilation resulting in death was identified in two adult black-footed ferrets (Mustela nigripes) housed at the Smithsonian Conservation Biology Institute in Front Royal, Virginia. Both individuals were adult males (3 and 5 yr) and previously clinically healthy prior to the event. The etiology of gastric dilation in both cases could not be definitively determined, and necropsy revealed severe cardiovascular compromise secondary to bloat. Limited literature is available regarding a syndrome of this type in adult black-footed ferrets. Differential diagnoses considered included gastric dilatation volvulus (GDV), severe gastric distention of unknown origin, and gastric outflow obstruction. Given the severity of this syndrome and the findings in these two cases, acute gastric dilation should be considered in black-footed ferrets presenting with acute abdominal distention, respiratory distress, and cardiovascular compromise. PMID:27010305

  5. Auditory gap-in-noise detection behavior in ferrets and humans.

    PubMed

    Gold, Joshua R; Nodal, Fernando R; Peters, Fabian; King, Andrew J; Bajo, Victoria M

    2015-08-01

    The precise encoding of temporal features of auditory stimuli by the mammalian auditory system is critical to the perception of biologically important sounds, including vocalizations, speech, and music. In this study, auditory gap-detection behavior was evaluated in adult pigmented ferrets (Mustelid putorius furo) using bandpassed stimuli designed to widely sample the ferret's behavioral and physiological audiogram. Animals were tested under positive operant conditioning, with psychometric functions constructed in response to gap-in-noise lengths ranging from 3 to 270 ms. Using a modified version of this gap-detection task, with the same stimulus frequency parameters, we also tested a cohort of normal-hearing human subjects. Gap-detection thresholds were computed from psychometric curves transformed according to signal detection theory, revealing that for both ferrets and humans, detection sensitivity was worse for silent gaps embedded within low-frequency noise compared with high-frequency or broadband stimuli. Additional psychometric function analysis of ferret behavior indicated effects of stimulus spectral content on aspects of behavioral performance related to decision-making processes, with animals displaying improved sensitivity for broadband gap-in-noise detection. Reaction times derived from unconditioned head-orienting data and the time from stimulus onset to reward spout activation varied with the stimulus frequency content and gap length, as well as the approach-to-target choice and reward location. The present study represents a comprehensive evaluation of gap-detection behavior in ferrets, while similarities in performance with our human subjects confirm the use of the ferret as an appropriate model of temporal processing. PMID:26052794

  6. Digging behaviors of radio-tagged black-footed ferrets near Meeteetse, Wyoming, 1981-1984

    USGS Publications Warehouse

    Biggins, Dean E.; Hanebury, Louis R.; Fagerstone, Kathleen A.

    2012-01-01

    Intensive radio-tracking during August–December enabled us to collect detailed information on digging behaviors of a small sample of black-footed ferrets (Mustela nigripes) occupying colonies of white-tailed prairie dogs (Cynomys leucurus). A sample of 33 prairie dogs, also radio-tagged, progressively ceased aboveground activity during late summer and fall, presumably as they descended into burrows to hibernate. Most of the time ferrets spent digging was in November–December when >95% of the radio-tagged prairie dogs were inactive, suggesting that digging was primarily to excavate hibernating prey. Although 43.9% of the burrow openings were estimated to be in large mounds, which are common on colonies of white-tailed prairie dogs, all of a sample of 17 deposits of soil (diggings) made by ferrets were excavated at small mounds or nonmounded openings. The average duration of 23 nocturnal sessions of digging by ferrets was 112.2 minutes. A digging session consisted of multiple bouts of soil movement typically lasting about 5 min, and sessions were separated by pauses above- or belowground lasting several minutes. Bouts of moving soil from a burrow involved round-trips of 12.5–30.3 s to remove an average of 35 cm3 of soil per trip. These digging bouts are energetically costly for ferrets. One female moved 16.8 kg of soil an estimated 3.3 m during bouts having a cumulative duration of 178 minutes, removing a soil plug estimated to be 178 cm long. Increasing evidence suggests that some behaviors of ferrets and prairie dogs are coevolutionary responses between this highly specialized predator and its prairie dog prey.

  7. Auditory gap-in-noise detection behavior in ferrets and humans.

    PubMed

    Gold, Joshua R; Nodal, Fernando R; Peters, Fabian; King, Andrew J; Bajo, Victoria M

    2015-08-01

    The precise encoding of temporal features of auditory stimuli by the mammalian auditory system is critical to the perception of biologically important sounds, including vocalizations, speech, and music. In this study, auditory gap-detection behavior was evaluated in adult pigmented ferrets (Mustelid putorius furo) using bandpassed stimuli designed to widely sample the ferret's behavioral and physiological audiogram. Animals were tested under positive operant conditioning, with psychometric functions constructed in response to gap-in-noise lengths ranging from 3 to 270 ms. Using a modified version of this gap-detection task, with the same stimulus frequency parameters, we also tested a cohort of normal-hearing human subjects. Gap-detection thresholds were computed from psychometric curves transformed according to signal detection theory, revealing that for both ferrets and humans, detection sensitivity was worse for silent gaps embedded within low-frequency noise compared with high-frequency or broadband stimuli. Additional psychometric function analysis of ferret behavior indicated effects of stimulus spectral content on aspects of behavioral performance related to decision-making processes, with animals displaying improved sensitivity for broadband gap-in-noise detection. Reaction times derived from unconditioned head-orienting data and the time from stimulus onset to reward spout activation varied with the stimulus frequency content and gap length, as well as the approach-to-target choice and reward location. The present study represents a comprehensive evaluation of gap-detection behavior in ferrets, while similarities in performance with our human subjects confirm the use of the ferret as an appropriate model of temporal processing.

  8. Minimizing Trauma to the Upper Airway: A Ferret Model of Neonatal Intubation

    PubMed Central

    Kircher, Sara S; Murray, Len E; Juliano, Michael L

    2009-01-01

    Our objective was to determine whether an adult ferret can be intubated as many as 10 times per training session without resulting in trauma to the upper airway. In this program, 8 male ferrets rotated through intubation laboratories, limiting the use of each animal to once every 3 mo. Animals were examined by the veterinary staff after intubations to assess for trauma to upper airway tissue. Each examination was given a trauma grade of 0 for no visible signs of trauma, 1 if erythema of the larynx was present, 2 if visible excoriation of the mucus membranes was present, and 3 if bleeding (frank hemorrhage) was observed. The number of intubation attempts was restricted to 10 per animal per training session. A total of 170 intubations were completed on the ferrets during a 12-mo period. The average number of intubations per laboratory was 8.1 intubations per ferret. In addition, 1.8% of the intubations resulted in erythema (score, 1) after training, and 0.6% of the intubations resulted in excoriation (score, 2). Frank hemorrhage (score, 3) was not noted. The overall percentage of intubations resulting in any trauma during a training session was 0.02%. None of the animals have experienced any major complications to date. This ongoing training program has been used to teach neonatal intubation skills to emergency medicine residents for the past 12 mo. Ensuring the health and safety of the ferrets was paramount. Our results suggest that as many as 10 intubation attempts per session can be performed safely on each ferret without causing excessive trauma. PMID:19930827

  9. Evaluation of a black-footed ferret resource utilization function model

    USGS Publications Warehouse

    Eads, D.A.; Millspaugh, J.J.; Biggins, D.E.; Jachowski, D.S.; Livieri, T.M.

    2011-01-01

    Resource utilization function (RUF) models permit evaluation of potential habitat for endangered species; ideally such models should be evaluated before use in management decision-making. We evaluated the predictive capabilities of a previously developed black-footed ferret (Mustela nigripes) RUF. Using the population-level RUF, generated from ferret observations at an adjacent yet distinct colony, we predicted the distribution of ferrets within a black-tailed prairie dog (Cynomys ludovicianus) colony in the Conata Basin, South Dakota, USA. We evaluated model performance, using data collected during post-breeding spotlight surveys (2007-2008) by assessing model agreement via weighted compositional analysis and count-metrics. Compositional analysis of home range use and colony-level availability, and core area use and home range availability, demonstrated ferret selection of the predicted Very high and High occurrence categories in 2007 and 2008. Simple count-metrics corroborated these findings and suggested selection of the Very high category in 2007 and the Very high and High categories in 2008. Collectively, these results suggested that the RUF was useful in predicting occurrence and intensity of space use of ferrets at our study site, the 2 objectives of the RUF. Application of this validated RUF would increase the resolution of habitat evaluations, permitting prediction of the distribution of ferrets within distinct colonies. Additional model evaluation at other sites, on other black-tailed prairie dog colonies of varying resource configuration and size, would increase understanding of influences upon model performance and the general utility of the RUF. ?? 2011 The Wildlife Society.

  10. Proceedings of the Black-footed Ferret & Prairie Dog Workshop, September 4-6, 1973

    USGS Publications Warehouse

    Linder, R.L., (compiler); Hillman, C.N., (compiler)

    1973-01-01

    Both State and Federal agencies have been working with the black-footed ferret and prairie dog during the past few years. Much of the work is not extensive enough for publication in scientific journals and is, therefore, not reported. The objective of this Workshop was to bring workers together for discussion of the current status of the two species. Each of the Conservation Departments in the states and provinces within the former range of the prairie dog and the black-footed ferret was invited to participate. Federal agencies were also invited to report on current programs in progress on public lands.

  11. Anatomy and Disorders of the Oral Cavity of Ferrets and Other Exotic Companion Carnivores.

    PubMed

    Johnson-Delaney, Cathy A

    2016-09-01

    Exotic companion carnivores such as ferrets, skunks, fennec foxes, coatimundis, raccoons, and kinkajous presented in clinical practice share similar dental anatomy, function, and diseases. The domestic ferret serves as the representative species for this group with its anatomy, diseases, and conditions described in detail. Dog and cat guidelines for veterinary and home care seem to be relevant and applicable, including dental endodontic procedures. Annual or biannual dental examinations and prophylaxis are recommended. The most common dental and oral problems are tooth wear, plaque and calculus, teeth fractures, gingivitis and periodontitis, tooth loss, abscesses, oral ulceration, tonsillitis, and neoplasia. PMID:27497211

  12. Production of infectious ferret hepatitis E virus in a human hepatocarcinoma cell line PLC/PRF/5.

    PubMed

    Li, Tian-Cheng; Yoshizaki, Sayaka; Yang, Tingting; Kataoka, Michiyo; Nakamura, Tomofumi; Ami, Yasushi; Yuriko, Suzaki; Takeda, Naokazu; Wakita, Takaji

    2016-02-01

    A strain of ferret hepatitis E virus (HEV), sF4370, isolated from an imported ferret was used to inoculate a human hepatocarcinoma cell line, PLC/PRF/5. The virus genome and capsid protein were detected in the cell culture supernatant. Immunofluorescence microscopy indicated that the capsid protein was located in the cytoplasm. The virus particles were purified from the culture supernatant by sucrose gradient ultracentrifugation. The capsid protein with molecular mass of ∼72 kDa was detected in fractions with density of 1.150-1.162 g/cm(3), and particles of ferret HEV was associated with cell membrane. The virus recovered from the supernatant was serially passaged with PLC/PRF/5 cells and had the ability to infect ferrets by oral inoculation, indicating that the ferret HEV grown in PLC/PRF/5 was infectious. The establishment of ferret HEV cell culture system might be useful to understand the life cycle, mechanism of infection and replication of ferret HEV.

  13. Production of infectious ferret hepatitis E virus in a human hepatocarcinoma cell line PLC/PRF/5.

    PubMed

    Li, Tian-Cheng; Yoshizaki, Sayaka; Yang, Tingting; Kataoka, Michiyo; Nakamura, Tomofumi; Ami, Yasushi; Yuriko, Suzaki; Takeda, Naokazu; Wakita, Takaji

    2016-02-01

    A strain of ferret hepatitis E virus (HEV), sF4370, isolated from an imported ferret was used to inoculate a human hepatocarcinoma cell line, PLC/PRF/5. The virus genome and capsid protein were detected in the cell culture supernatant. Immunofluorescence microscopy indicated that the capsid protein was located in the cytoplasm. The virus particles were purified from the culture supernatant by sucrose gradient ultracentrifugation. The capsid protein with molecular mass of ∼72 kDa was detected in fractions with density of 1.150-1.162 g/cm(3), and particles of ferret HEV was associated with cell membrane. The virus recovered from the supernatant was serially passaged with PLC/PRF/5 cells and had the ability to infect ferrets by oral inoculation, indicating that the ferret HEV grown in PLC/PRF/5 was infectious. The establishment of ferret HEV cell culture system might be useful to understand the life cycle, mechanism of infection and replication of ferret HEV. PMID:26763355

  14. Developmental remodeling of corticocortical feedback circuits in ferret visual cortex.

    PubMed

    Khalil, Reem; Levitt, Jonathan B

    2014-10-01

    Visual cortical areas in the mammalian brain are linked through a system of interareal feedforward and feedback connections, which presumably underlie different visual functions. We characterized the refinement of feedback projections to primary visual cortex (V1) from multiple sources in juvenile ferrets ranging in age from 4-10 weeks postnatal. We studied whether the refinement of different aspects of feedback circuitry from multiple visual cortical areas proceeds at a similar rate in all areas. We injected the neuronal tracer cholera toxin B (CTb) into V1 and mapped the areal and laminar distribution of retrogradely labeled cells in extrastriate cortex. Around the time of eye opening at 4 weeks postnatal, the retinotopic arrangement of feedback appears essentially adult-like; however, suprasylvian cortex supplies the greatest proportion of feedback, whereas area 18 supplies the greatest proportion in the adult. The density of feedback cells and the ratio of supragranular/infragranular feedback contribution declined in this period at a similar rate in all cortical areas. We also found significant feedback to V1 from layer IV of all extrastriate areas. The regularity of cell spacing, the proportion of feedback arising from layer IV, and the tangential extent of feedback in each area all remained essentially unchanged during this period, except for the infragranular feedback source in area 18, which expanded. Thus, while much of the basic pattern of cortical feedback to V1 is present before eye opening, there is major synchronous reorganization after eye opening, suggesting a crucial role for visual experience in this remodeling process.

  15. Black-footed ferrets and recreational shooting influence the attributes of black-tailed prairie dog burrows

    USGS Publications Warehouse

    Biggins, Dean E.; Ramakrishnan, Shantini; Goldberg, Amanda R.; Eads, David A.

    2012-01-01

    Black-tailed prairie dogs (Cynomys ludovicianus) plug burrows occupied by black-footed ferrets (Mustela nigripes), and they also plug burrows to entomb dead prairie dogs. We further evaluated these phenomena by sampling connectivity and plugging of burrow openings on prairie dog colonies occupied by ferrets, colonies where recreational shooting was allowed, and colonies with neither shooting nor ferrets. We counted burrow openings on line surveys and within plots, classified surface plugging, and used an air blower to examine subsurface connectivity. Colonies with ferrets had lower densities of openings, fewer connected openings (suggesting increased subsurface plugging), and more surface plugs compared to colonies with no known ferrets. Colonies with recreational shooting had the lowest densities of burrow openings, and line-survey data suggested colonies with shooting had intermediate rates of surface plugging. The extent of surface and subsurface plugging could have consequences for the prairie dog community by changing air circulation and escape routes of burrow systems and by altering energetic relationships. Burrow plugging might reduce prairie dogs' risk of predation by ferrets while increasing risk of predation by American badgers (Taxidea taxus); however, the complexity of the trade-off is increased if plugging increases the risk of predation on ferrets by badgers. Prairie dogs expend more energy plugging and digging when ferrets or shooting are present, and ferrets increase their energy expenditures when they dig to remove those plugs. Microclimatic differences in plugged burrow systems may play a role in flea ecology and persistence of the flea-borne bacterium that causes plague (Yersinia pestis).

  16. Using the Ferret as an Animal Model for Investigating Influenza Antiviral Effectiveness

    PubMed Central

    Oh, Ding Y.; Hurt, Aeron C.

    2016-01-01

    The concern of the emergence of a pandemic influenza virus has sparked an increased effort toward the development and testing of novel influenza antivirals. Central to this is the animal model of influenza infection, which has played an important role in understanding treatment effectiveness and the effect of antivirals on host immune responses. Among the different animal models of influenza, ferrets can be considered the most suitable for antiviral studies as they display most of the human-like symptoms following influenza infections, they can be infected with human influenza virus without prior viral adaptation and have the ability to transmit influenza virus efficiently between one another. However, an accurate assessment of the effectiveness of an antiviral treatment in ferrets is dependent on three major experimental considerations encompassing firstly, the volume and titer of virus, and the route of viral inoculation. Secondly, the route and dose of drug administration, and lastly, the different methods used to assess clinical symptoms, viral shedding kinetics and host immune responses in the ferrets. A good understanding of these areas is necessary to achieve data that can accurately inform the human use of influenza antivirals. In this review, we discuss the current progress and the challenges faced in these three major areas when using the ferret model to measure influenza antiviral effectiveness. PMID:26870031

  17. Evaluation of MDCK cell-derived influenza H7N9 vaccine candidates in ferrets.

    PubMed

    Chia, Min-Yuan; Hu, Alan Yung-Chih; Tseng, Yu-Fen; Weng, Tsai-Chuan; Lai, Chia-Chun; Lin, Jun-Yang; Chen, Po-Ling; Wang, Ya-Fang; Chao, Sin-Ru; Chang, Jui-Yuan; Hwang, Yi-Shiuh; Yeh, Chia-Tsui; Yu, Cheng-Ping; Chen, Yee-Chun; Su, Ih-Jen; Lee, Min-Shi

    2015-01-01

    Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300 μg aluminum hydroxide, 1.5 μg HA, and 1.5 μg HA plus 300 μg aluminum hydroxide) were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA) inhibition and neutralizing antibodies were <10 and <40 for the control group (adjuvant only), 17 and 80 for the unadjuvanted (HA only) group, and 190 and 640 for the adjuvanted group (HA plus adjuvant), respectively. After challenge with wild-type influenza H7N9 viruses, virus titers in respiratory tracts of the adjuvanted group were significantly lower than that in the control, and unadjuvanted groups. MDCK cell-derived influenza H7N9 whole virus vaccine candidate is immunogenic and protective in ferrets and clinical development is highly warranted. PMID:25799397

  18. Effects of vomeronasal organ removal on olfactory sex discrimination and odor preferences of female ferrets.

    PubMed

    Woodley, S K; Cloe, A L; Waters, P; Baum, M J

    2004-10-01

    Previous research suggests that body odorants, including anal scents and urinary odors, contribute to sex discrimination and mate identification in European ferrets of both sexes. We assessed the possible role of the vomeronasal organ (VNO) in these functions by surgically removing the organ bilaterally in sexually experienced female ferrets. Lesioned (VNOx) and sham-operated control (VNOi) females reliably discriminated between male- and female-derived anal scent gland as well as fresh urinary odors in habituation/dishabituation tests. However, VNOi females spent significantly more time than VNOx subjects investigating male urinary odors in these tests. Also, VNOi females, but not VNOx subjects, preferred to investigate day-old male versus female urine spots as well as wooden blocks that had previously been soiled by male versus female ferrets. Both groups of female ferrets preferred to approach volatile odors from a breeding male instead of an estrous female in Y-maze tests and both groups showed similar levels of receptive sexual behavior in response to a male's neck grip. The VNO is apparently not required for olfactory sex discrimination or mate recognition in this carnivore, but instead may play a role in promoting continued contact with nonvolatile body odors previously deposited by opposite-sex conspecifics during territorial scent marking. PMID:15466811

  19. A preliminary study of sleep ontogenesis in the ferret (Mustela putorius furo)

    PubMed Central

    Thurber, Allison; Jha, Sushil K.; Coleman, Tammi; Frank, Marcos G.

    2008-01-01

    We investigated sleep ontogenesis in the ferret—a placental mammal that is highly altricial compared to other mammalian species. Because altriciality is linked with elevated REM sleep amounts during infancy, it was expected that ferret kits would display very high levels of this state. Longitudinal polysomnographic measurements were made from 8 ferret kits from approximately eye-opening (postnatal day [P]30)-P50 using an experimental routine that minimized the effects of maternal separation. These data were compared to values from 8 adult ferrets (>3 months of age) and 6 neonatal cats (mean age: P31.7). We find that the polygraphic features of rapid-eye-movement (REM) and non-REM (NREM) sleep are present by at least P30. Over the next 2 weeks, REM sleep amounts slightly declined while wakefulness and NREM sleep amounts increased. However, a comparison to published values from developing cats and rats showed that the ferret did not exhibit a disproportionate amount of REM sleep at similar postnatal ages or relative to a common developmental milestone (eye-opening). PMID:18243360

  20. Is the ferret a suitable species for studying perinatal brain injury?

    PubMed

    Empie, Kristen; Rangarajan, Vijayeta; Juul, Sandra E

    2015-10-01

    Complications of prematurity often disrupt normal brain development and/or cause direct damage to the developing brain, resulting in poor neurodevelopmental outcomes. Physiologically relevant animal models of perinatal brain injury can advance our understanding of these influences and thereby provide opportunities to develop therapies and improve long-term outcomes. While there are advantages to currently available small animal models, there are also significant drawbacks that have limited translation of research findings to humans. Large animal models such as newborn pig, sheep and nonhuman primates have complex brain development more similar to humans, but these animals are expensive, and developmental testing of sheep and piglets is limited. Ferrets (Mustela putorius furo) are born lissencephalic and undergo postnatal cortical folding to form complex gyrencephalic brains. This review examines whether ferrets might provide a novel intermediate animal model of neonatal brain disease that has the benefit of a gyrified, altricial brain in a small animal. It summarizes attributes of ferret brain growth and development that make it an appealing animal in which to model perinatal brain injury. We postulate that because of their innate characteristics, ferrets have great potential in neonatal neurodevelopmental studies.

  1. Ferret and Pig Models of Cystic Fibrosis: Prospects and Promise for Gene Therapy

    PubMed Central

    Yan, Ziying; Stewart, Zoe A.; Sinn, Patrick L.; Olsen, John C.; Hu, Jim; McCray, Paul B.

    2015-01-01

    Abstract Large animal models of genetic diseases are rapidly becoming integral to biomedical research as technologies to manipulate the mammalian genome improve. The creation of cystic fibrosis (CF) ferrets and pigs is an example of such progress in animal modeling, with the disease phenotypes in the ferret and pig models more reflective of human CF disease than mouse models. The ferret and pig CF models also provide unique opportunities to develop and assess the effectiveness of gene and cell therapies to treat affected organs. In this review, we examine the organ disease phenotypes in these new CF models and the opportunities to test gene therapies at various stages of disease progression in affected organs. We then discuss the progress in developing recombinant replication-defective adenoviral, adeno-associated viral, and lentiviral vectors to target genes to the lung and pancreas in ferrets and pigs, the two most affected organs in CF. Through this review, we hope to convey the potential of these new animal models for developing CF gene and cell therapies. PMID:25675143

  2. Viscoelastic properties of the ferret brain measured in vivo at multiple frequencies by magnetic resonance elastography

    PubMed Central

    Feng, Y.; Clayton, E.H.; Chang, Y.; Okamoto, R.J.; Bayly, P.V.

    2013-01-01

    Characterization of the dynamic mechanical behavior of brain tissue is essential for understanding and simulating the mechanisms of traumatic brain injury (TBI). Changes in mechanical properties may also reflect changes in the brain due to aging or disease. In this study, we used magnetic resonance elastography (MRE) to measure the viscoelastic properties of ferret brain tissue in vivo. Three-dimensional (3D) displacement fields were acquired during wave propagation in the brain induced by harmonic excitation of the skull at 400 Hz, 600 Hz and 800 Hz. Shear waves with wavelengths on the order of millimeters were clearly visible in the displacement field, in strain fields, and in the curl of displacement field (which contains no contributions from longitudinal waves). Viscoelastic parameters (storage and loss moduli) governing dynamic shear deformation were estimated in gray and white matter for these excitation frequencies. To characterize the reproducibility of measurements, two ferrets were studied on three different dates each. Estimated viscoelastic properties of white matter in the ferret brain were generally similar to those of gray matter and consistent between animals and scan dates. In both tissue types G′ increased from approximately 3 kPa at 400 Hz to 7 kPa at 800 Hz and G″ increased from approximately 1 kPa at 400 Hz to 2 kPa at 800 Hz. These measurements of shear wave propagation in the ferret brain can be used to both parameterize and validate finite element models of brain biomechanics. PMID:23352648

  3. Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets

    PubMed Central

    Herfst, Sander; Schrauwen, Eefje J. A.; Linster, Martin; Chutinimitkul, Salin; de Wit, Emmie; Munster, Vincent J.; Sorrell, Erin M.; Bestebroer, Theo M.; Burke, David F.; Smith, Derek J.; Rimmelzwaan, Guus F.; Osterhaus, Albert D. M. E.; Fouchier, Ron A. M.

    2016-01-01

    Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet (“airborne transmission”) between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets. None of the recipient ferrets died after airborne infection with the mutant A/H5N1 viruses. Four amino acid substitutions in the host receptor-binding protein hemagglutinin, and one in the polymerase complex protein basic polymerase 2, were consistently present in airborne-transmitted viruses. The transmissible viruses were sensitive to the antiviral drug oseltamivir and reacted well with antisera raised against H5 influenza vaccine strains. Thus, avian A/H5N1 influenza viruses can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host and therefore constitute a risk for human pandemic influenza. PMID:22723413

  4. Comparative analysis of aortic impedance and wave reflection in ferrets and dogs.

    PubMed

    Burattini, R; Campbell, K B

    2002-01-01

    Our modified version of the T-tube arterial model (consisting of two parallel, loss-free transmission paths terminating in lumped loads of complex and frequency-dependent nature) was applied to experimental measurements of ascending aortic pressure and of ascending and descending aortic flows taken from dogs and ferrets. Our aim was to provide quantitative evaluation of the aortic pressure and flow pulse wave components as they relate to the distribution of arterial properties and relate to wave travel and reflection in mammalians of consistently different size and shape. Estimated effective lengths (distances to effective reflection sites) of the head-end (d(h)) and body-end (d(b)) transmission paths were approximately 12 and 30 cm, respectively, in the dog and 6.5 and 13 cm, respectively, in the ferret. These lengths and distributions of estimated arterial properties were consistent with the difference in the body size and with the more central location of the heart in the ferret's body than it is in the dog's body. In both animal species the ascending aortic pressure and flow waves could be interpreted in terms of forward and reflected components arising from the two distinct effective reflection sites, although the higher d(h)/d(b) ratio in the ferret determined the presence of one broad, indistinct minimum in the modulus of ascending aortic impedance in the frequency range from 0 to 10 Hz, rather than two distinct minima as observed in the dog.

  5. Ferrets as sentinels of the presence of pathogenic Cryptococcus species in the Mediterranean environment.

    PubMed

    Morera, Neus; Hagen, Ferry; Juan-Sallés, Carles; Artigas, Carlos; Patricio, Rui; Serra, Juan Ignacio; Colom, Ma Francisca

    2014-08-01

    Cryptococcus gattii is a pathogenic environmental yeast that is considered to be emerging in different areas of the world including the Mediterranean Basin. Exposure to infection might be more likely in animals than in human beings, given their closer relationship with the natural habitat of the yeast, vegetation and soil. Thus, animals, and especially pets, can act as indicators of the presence of this yeast in a determined area. Domestic ferrets (Mustela putorius furo) have become common pets in the past 10-20 years. Their natural behavior of sniffing around and going inside narrow spaces makes them prone to contact with decaying organic matter and soil, the substrate for Cryptococcus species. This study describes two cases of cryptococcosis in ferrets in the Iberian Peninsula and Balearic Islands and documents a relationship of ferret cryptococcosis with environmental isolates in the same locations. Here, we emphasize the importance of how an adequate identification and environmental search of the yeast leads to a better understanding of the epidemiology of cryptococcosis and suggests ferrets may act as sentinels for this fungal disease. PMID:24962111

  6. Ferrets exclusively synthesize Neu5Ac and express naturally humanized influenza A virus receptors

    PubMed Central

    Ng, Preston S.K.; Böhm, Raphael; Hartley-Tassell, Lauren E.; Steen, Jason A.; Wang, Hui; Lukowski, Samuel W.; Hawthorne, Paula L.; Trezise, Ann E.O.; Coloe, Peter J.; Grimmond, Sean M.; Haselhorst, Thomas; von Itzstein, Mark; Paton, Adrienne W.; Paton, James C.; Jennings, Michael P.

    2014-01-01

    Mammals express the sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) on cell surfaces, where they act as receptors for pathogens, including influenza A virus (IAV). Neu5Gc is synthesized from Neu5Ac by the enzyme cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH). In humans, this enzyme is inactive and only Neu5Ac is produced. Ferrets are susceptible to human-adapted IAV strains and have been the dominant animal model for IAV studies. Here we show that ferrets, like humans, do not synthesize Neu5Gc. Genomic analysis reveals an ancient, nine-exon deletion in the ferret CMAH gene that is shared by the Pinnipedia and Musteloidia members of the Carnivora. Interactions between two human strains of IAV with the sialyllactose receptor (sialic acid—α2,6Gal) confirm that the type of terminal sialic acid contributes significantly to IAV receptor specificity. Our results indicate that exclusive expression of Neu5Ac contributes to the susceptibility of ferrets to human-adapted IAV strains. PMID:25517696

  7. Cytological analysis of bronchoalveolar lavage fluid acquired by bronchoscopy in healthy ferrets: A pilot study

    PubMed Central

    Bercier, Marjorie; Langlois, Isabelle; Dunn, Marilyn; Hélie, Pierre; Burns, Patrick; Gara-Boivin, Carolyn

    2016-01-01

    The objective of this study was to investigate the normal cytological evaluation of bronchoalveolar lavage (BAL) fluid in healthy adult ferrets (N = 12). These ferrets underwent bronchoscopy and BAL using sterile saline [1.5 mL/kg body weight (BW)]. Percentage of fluid recovered, total leukocyte count, differential leukocyte count, and cell count of the epithelial lining fluid (ELF) were determined. The mean percentage of lavage volume recovered from the right lung and left lung were 67.8 ± 14.9% and 69.7 ± 20.0%, respectively. Gender (P = 0.12) and weight (P = 0.17) did not significantly affect the mean percentage of recovered volume. The mean percentage of recovered volume (P = 0.47) and the mean leukocyte count (P = 0.17) from the right and left lung were not significantly different. Macrophages were the main leukocyte component of the lavages, followed by neutrophils, lymphocytes, and eosinophils. The mean proportion of ELF in BAL fluid was 9.3 ± 3.7% v/v. Bronchoscopy is clinically useful for collecting good quality BAL samples for cytological analysis in ferrets. The leucocyte differential was established, which may help veterinarians to make better clinical decisions when treating respiratory disease. Further studies are required with a larger group in order to establish the healthy reference intervals for BAL values in ferrets. PMID:26733735

  8. Is the ferret a suitable species for studying perinatal brain injury?

    PubMed Central

    Empie, Kristen; Rangarajan, Vijayeta; Juul, Sandra E.

    2016-01-01

    Complications of prematurity often disrupt normal brain development and/or cause direct damage to the developing brain, resulting in poor neurodevelopmental outcomes. Physiologically relevant animal models of perinatal brain injury can advance our understanding of these influences and thereby provide opportunities to develop therapies and improve long-term outcomes. While there are advantages to currently available small animal models, there are also significant drawbacks that have limited translation of research findings to humans. Large animal models such as newborn pig, sheep and nonhuman primates have complex brain development more similar to humans, but these animals are expensive, and developmental testing of sheep and piglets is limited. Ferrets (Mustela putorius furo) are born lissencephalic and undergo postnatal cortical folding to form complex gyrencephalic brains. This review examines whether ferrets might provide a novel intermediate animal model of neonatal brain disease that has the benefit of a gyrified, altricial brain in a small animal. It summarizes attributes of ferret brain growth and development that make it an appealing animal in which to model perinatal brain injury. We postulate that because of their innate characteristics, ferrets have great potential in neonatal neurodevelopmental studies. PMID:26102988

  9. The Nature of Exposure Drives Transmission of Nipah Viruses from Malaysia and Bangladesh in Ferrets

    PubMed Central

    Clayton, Bronwyn A.; Middleton, Deborah; Arkinstall, Rachel; Frazer, Leah; Wang, Lin-Fa; Marsh, Glenn A.

    2016-01-01

    Person-to-person transmission is a key feature of human Nipah virus outbreaks in Bangladesh. In contrast, in an outbreak of Nipah virus in Malaysia, people acquired infections from pigs. It is not known whether this important epidemiological difference is driven primarily by differences between NiV Bangladesh (NiV-BD) and Malaysia (NiV-MY) at a virus level, or by environmental or host factors. In a time course study, ferrets were oronasally exposed to equivalent doses of NiV-BD or NiV-MY. More rapid onset of productive infection and higher levels of virus replication in respiratory tract tissues were seen for NiV-BD compared to NiV-MY, corroborating our previous report of increased oral shedding of NiV-BD in ferrets and suggesting a contributory mechanism for increased NiV-BD transmission between people compared to NiV-MY. However, we recognize that transmission occurs within a social and environmental framework that may have an important and differentiating role in NiV transmission rates. With this in mind, ferret-to-ferret transmission of NiV-BD and NiV-MY was assessed under differing viral exposure conditions. Transmission was not identified for either virus when naïve ferrets were cohoused with experimentally-infected animals. In contrast, all naïve ferrets developed acute infection following assisted and direct exposure to oronasal fluid from animals that were shedding either NiV-BD or NiV-MY. Our findings for ferrets indicate that, although NiV-BD may be shed at higher levels than NiV-MY, transmission risk may be equivalently low under exposure conditions provided by cohabitation alone. In contrast, active transfer of infected bodily fluids consistently results in transmission, regardless of the virus strain. These observations suggest that the risk of NiV transmission is underpinned by social and environmental factors, and will have practical implications for managing transmission risk during outbreaks of human disease. PMID:27341030

  10. Auditory Gap-in-Noise Detection Behavior in Ferrets and Humans

    PubMed Central

    2015-01-01

    The precise encoding of temporal features of auditory stimuli by the mammalian auditory system is critical to the perception of biologically important sounds, including vocalizations, speech, and music. In this study, auditory gap-detection behavior was evaluated in adult pigmented ferrets (Mustelid putorius furo) using bandpassed stimuli designed to widely sample the ferret’s behavioral and physiological audiogram. Animals were tested under positive operant conditioning, with psychometric functions constructed in response to gap-in-noise lengths ranging from 3 to 270 ms. Using a modified version of this gap-detection task, with the same stimulus frequency parameters, we also tested a cohort of normal-hearing human subjects. Gap-detection thresholds were computed from psychometric curves transformed according to signal detection theory, revealing that for both ferrets and humans, detection sensitivity was worse for silent gaps embedded within low-frequency noise compared with high-frequency or broadband stimuli. Additional psychometric function analysis of ferret behavior indicated effects of stimulus spectral content on aspects of behavioral performance related to decision-making processes, with animals displaying improved sensitivity for broadband gap-in-noise detection. Reaction times derived from unconditioned head-orienting data and the time from stimulus onset to reward spout activation varied with the stimulus frequency content and gap length, as well as the approach-to-target choice and reward location. The present study represents a comprehensive evaluation of gap-detection behavior in ferrets, while similarities in performance with our human subjects confirm the use of the ferret as an appropriate model of temporal processing. PMID:26052794

  11. Proceedings of the symposium on the management of prairie dog complexes for the reintroduction of the black-footed ferret

    USGS Publications Warehouse

    Oldemeyer, John L.; Biggins, Dean E.; Miller, Brian J.; Crete, Ronald

    1993-01-01

    The workshop featured a review of current knowledge in the biology of prairie dogs in the context of managing black-footed ferret habitat. The review addressed two main components. The first consisted of a series of papers on prairie dog habitat and biology. The second component of the workshop was a summary of the participants' discussion about managing prairie dog complexes. This discussion was based on the previously identified papers and profited from the participants' expertise on the ecology of black-footed ferrets and prairie dogs. The report provides current and comprehensive information about management of habitat for prairie dogs and black-footed ferrets and is a useful guide for agencies and individuals that manage black-footed ferrets.

  12. Comparison of capture-recapture and visual count indices of prairie dog densities in black-footed ferret habitat

    USGS Publications Warehouse

    Fagerstone, Kathleen A.; Biggins, Dean E.

    1986-01-01

    Black-footed ferrets (Mustela nigripes) are dependent on prairie dogs (Cynomys spp.) for food and on their burrows for shelter and rearing young. A stable prairie dog population may therefore be the most important factor determining the survival of ferrets. A rapid method of determining prairie dog density would be useful for assessing prairie dog density in colonies currently occupied by ferrets and for selecting prairie dog colonies in other areas for ferret translocation. This study showed that visual counts can provide a rapid density estimate. Visual counts of white-tailed prairie dogs (Cynomys leucurus) were significantly correlated (r = 0.95) with mark-recapture population density estimates on two study areas near Meeteetse, Wyoming. Suggestions are given for use of visual counts.

  13. The comparison of pathology in ferrets infected by H9N2 avian influenza viruses with different genomic features.

    PubMed

    Gao, Rongbao; Bai, Tian; Li, Xiaodan; Xiong, Ying; Huang, Yiwei; Pan, Ming; Zhang, Ye; Bo, Hong; Zou, Shumei; Shu, Yuelong

    2016-01-15

    H9N2 avian influenza virus circulates widely in poultry and has been responsible for sporadic human infections in several regions. Few studies have been conducted on the pathogenicity of H9N2 AIV isolates that have different genomic features. We compared the pathology induced by a novel reassortant H9N2 virus and two currently circulating H9N2 viruses that have different genomic features in ferrets. The results showed that the three viruses can induce infections with various amounts of viral shedding in ferrets. The novel H9N2 induced respiratory infection, but no pathological lesions were observed in lung tissues. The other two viruses induced mild to intermediate pathological lesions in lung tissues, although the clinical signs presented mildly in ferrets. The pathological lesions presented a diversity consistent with viral replication in ferrets. PMID:26638019

  14. Epidemic and maintenance of rabies in Chinese ferret badgers (Melogale moschata) indicated by epidemiology and the molecular signatures of rabies viruses.

    PubMed

    Zhang, Shoufeng; Liu, Ye; Hou, Yanli; Zhao, Jinghui; Zhang, Fei; Wang, Ying; Hu, Rongliang

    2013-06-01

    An epidemic of Chinese ferret badger-associated human rabies was investigated in Wuyuan county, Jiangxi province and rabies viruses isolates from ferret badgers in different districts in Jiangxi and Zhejiang provinces were sequenced with their nucleotides and amino acids and aligned for epidemiological analysis. The results showed that the human rabies in Wuyuan are only associated with ferret badger bites; the rabies virus can be isolated in a high percentage of ferret badgers in the epidemic areas in Jiangxi and Zhejiang provinces; the isolates share the same molecular features in nucleotides and have characteristic amino acid signatures, i.e., 2 sites in the nucleoprotein and 3 sites in the glycoprotein, that are distinct from virus isolates from dogs in the same region. We conclude that rabies in Chinese ferret badgers has formed an independent transmission cycle and ferret badgers may serve as another important rabies reservoir independent of dog rabies in China.

  15. Inter‐ and intraspecies transmission of canine influenza virus (H3N2) in dogs, cats, and ferrets

    PubMed Central

    Kim, Hyekwon; Song, Daesub; Moon, Hyoungjoon; Yeom, Minjoo; Park, Seongjun; Hong, Minki; Na, Woonseong; Webby, Richard J.; Webster, Robert G.; Park, Bongkyun; Kim, Jeong‐Ki; Kang, Bokyu

    2012-01-01

    Background  The emergence of zoonotic viruses in domestic animals is a significant public health concern. Canine influenza virus (CIV) H3N2 is a virus that can infect companion animals and is, therefore, a potential public health concern. Objective  This study investigated the inter‐ and intraspecies transmission of CIV among dogs, cats, and ferrets, under laboratory conditions, to determine whether transmission of the virus was possible between as well as within these domestic animal species. Method  The transmission routes for inter‐ and intraspecies transmission were airborne and direct contact, respectively. Transmission was conducted through intranasal infection of dogs followed by exposure to either cats or ferrets and by comingling infected and naïve animals of the same species. Results  The interspecies transmission of CIV H3N2 via airborne was only observed from dogs to cats and not from dogs to ferrets. However, direct intranasal infection of either cats or ferrets with CIV could induce influenza‐like clinical signs, viral shedding, and serological responses. Additionally, naïve cats and ferrets could be infected by CIV via direct contact with infected animals of the same species. Conclusion  Cats appear to be another susceptible host of CIV H3N2, whereas ferrets are not likely natural hosts. The molecular‐based mechanism of interspecies and intraspecies transmission of CIV H3N2 should be further studied. PMID:22616918

  16. Ectoparasites in black-footed ferrets (Mustela nigripes) from the largest reintroduced population of the Conata Basin, South Dakota, USA.

    PubMed

    Harris, Nyeema C; Livieri, Travis M; Dunn, Robert R

    2014-04-01

    The black-footed ferret, Mustela nigripes, is an endangered carnivore endemic to the grasslands of North America. We present the first investigation of ectoparasites associated with black-footed ferrets since reintroduction. We sampled more than 200 individuals from one of the largest and most successful reintroduced populations located in the Conata Basin of South Dakota, USA. We compared our findings with ectoparasite assemblages of sympatric carnivores and historic ferret records. We collected more than 1,000 ectoparasites consisting mainly of three flea and tick species, two of which were known historically from South Dakota. Despite our extensive sampling efforts, we did not detect any lice. This is notable because a putative host-specific louse, Neotrichodectes sp., was presumed to have gone extinct when black-footed ferrets were extirpated from the wild. The ectoparasite assemblage on black-footed ferrets comprised only generalist parasites, particularly those found on their prey such as prairie dogs (Cynomys sp.). Oropsylla hirsuta was the most abundant ectoparasite, representing 57% of all ectoparasites detected; a flea vector important in the persistence and transmission of plague. Black-footed ferrets like other endangered species undergo repeated parasite removal and vaccination efforts to facilitate population recovery, which may have unintentionally contributed to their depauperate ectoparasite community. PMID:24499333

  17. Recombinant F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against virulent Yersinia pestis infection

    USGS Publications Warehouse

    Rocke, T.E.; Mencher, J.; Smith, S.R.; Friedlander, A.M.; Andrews, G.P.; Baeten, L.A.

    2004-01-01

    Black-footed ferrets (Mustela nigripes) are highly susceptible to sylvatic plague, caused by the bacterium Yersinia pestis, and this disease has severely hampered efforts to restore ferrets to their historic range. A study was conducted to assess the efficacy of vaccination of black-footed ferrets against plague using a recombinant protein vaccine, designated F1-V, developed by personnel at the U.S. Army Medical Research Institute of Infectious Diseases. Seven postreproductive black-footed ferrets were immunized with the vaccine, followed by two booster immunizations on days 23 and 154; three control black-footed ferrets received a placebo. After the second immunization, antibody titers to both F1 and V antigen were found to be significantly higher in vaccinates than controls. On challenge with 7,800 colony-forming units of virulent plague by s.c. injection, the three control animals died within 3 days, but six of seven vaccinates survived with no ill effects. The seventh vaccinate died on day 8. These results indicate that black-footed ferrets can be immunized against plague induced by the s.c. route, similar to fleabite injection.

  18. Oseltamivir Population Pharmacokinetics in the Ferret: Model Application for Pharmacokinetic/Pharmacodynamic Study Design

    PubMed Central

    Reddy, Micaela B.; Yang, Kuo-Hsiung; Rao, Gauri; Rayner, Craig R.; Nie, Jing; Pamulapati, Chandrasena; Marathe, Bindumadhav M.; Forrest, Alan; Govorkova, Elena A.

    2015-01-01

    The ferret is a suitable small animal model for preclinical evaluation of efficacy of antiviral drugs against various influenza strains, including highly pathogenic H5N1 viruses. Rigorous pharmacokinetics/pharmacodynamics (PK/PD) assessment of ferret data has not been conducted, perhaps due to insufficient information on oseltamivir PK. Here, based on PK data from several studies on both uninfected and influenza-infected groups (i.e., with influenza A viruses of H5N1 and H3N2 subtypes and an influenza B virus) and several types of anesthesia we developed a population PK model for the active compound oseltamivir carboxylate (OC) in the ferret. The ferret OC population PK model incorporated delayed first-order input, two-compartment distribution, and first-order elimination to successfully describe OC PK. Influenza infection did not affect model parameters, but anesthesia did. The conclusion that OC PK was not influenced by influenza infection must be viewed with caution because the influenza infections in the studies included here resulted in mild clinical symptoms in terms of temperature, body weight, and activity scores. Monte Carlo simulations were used to determine that administration of a 5.08 mg/kg dose of oseltamivir phosphate to ferret every 12 h for 5 days results in the same median OC area under the plasma concentration-time curve 0–12 h (i.e., 3220 mg h/mL) as that observed in humans during steady state at the approved dose of 75 mg twice daily for 5 days. Modeling indicated that PK variability for OC in the ferret model is high, and can be affected by anesthesia. Therefore, for proper interpretation of PK/PD data, sparse PK sampling to allow the OC PK determination in individual animals is important. Another consideration in appropriate design of PK/PD studies is achieving an influenza infection with pronounced clinical symptoms and efficient virus replication, which will allow adequate evaluation of drug effects. PMID:26460484

  19. Oseltamivir Population Pharmacokinetics in the Ferret: Model Application for Pharmacokinetic/Pharmacodynamic Study Design.

    PubMed

    Reddy, Micaela B; Yang, Kuo-Hsiung; Rao, Gauri; Rayner, Craig R; Nie, Jing; Pamulapati, Chandrasena; Marathe, Bindumadhav M; Forrest, Alan; Govorkova, Elena A

    2015-01-01

    The ferret is a suitable small animal model for preclinical evaluation of efficacy of antiviral drugs against various influenza strains, including highly pathogenic H5N1 viruses. Rigorous pharmacokinetics/pharmacodynamics (PK/PD) assessment of ferret data has not been conducted, perhaps due to insufficient information on oseltamivir PK. Here, based on PK data from several studies on both uninfected and influenza-infected groups (i.e., with influenza A viruses of H5N1 and H3N2 subtypes and an influenza B virus) and several types of anesthesia we developed a population PK model for the active compound oseltamivir carboxylate (OC) in the ferret. The ferret OC population PK model incorporated delayed first-order input, two-compartment distribution, and first-order elimination to successfully describe OC PK. Influenza infection did not affect model parameters, but anesthesia did. The conclusion that OC PK was not influenced by influenza infection must be viewed with caution because the influenza infections in the studies included here resulted in mild clinical symptoms in terms of temperature, body weight, and activity scores. Monte Carlo simulations were used to determine that administration of a 5.08 mg/kg dose of oseltamivir phosphate to ferret every 12 h for 5 days results in the same median OC area under the plasma concentration-time curve 0-12 h (i.e., 3220 mg h/mL) as that observed in humans during steady state at the approved dose of 75 mg twice daily for 5 days. Modeling indicated that PK variability for OC in the ferret model is high, and can be affected by anesthesia. Therefore, for proper interpretation of PK/PD data, sparse PK sampling to allow the OC PK determination in individual animals is important. Another consideration in appropriate design of PK/PD studies is achieving an influenza infection with pronounced clinical symptoms and efficient virus replication, which will allow adequate evaluation of drug effects. PMID:26460484

  20. Thermal Stability and Interaction with Ferret Inflammatory Exudates of Two Clones of Influenza Virus of Differing Virulence for Both Ferrets and Man

    PubMed Central

    Sweet, C.; Bird, R. A.; Toms, G. L.; Woodward, C. G.; Smith, H.

    1977-01-01

    After intranasal inoculation of ferrets with influenza virus the upper respiratory tract infection diminishes during the second day and the onset of this reduction occurs earlier for an attenuated clone (64d) than for a virulent clone (7a) of the recombinant virus A/PR/8/34-A/England/939/69 (H3N2). The relevance of pyrexia and the nasal inflammatory response to this reduction in infection has been investigated. Egg-grown Clone 64d was more thermobile than Clone 7a at normal and pyrexial temperatures when suspended in egg allantoic fluid or phosphate-buffered saline. However, in infected nasal washes, both clones were rapidly inactivated when the washes were incubated at these temperatures. In vitro tests showed that both clones adsorbed to the phagocytes of peritoneal exudates from uninfected ferrets and nasal inflammatory exudates of ferrets infected with both clones. About 90% of the virus was adsorbed after 30 min at 0° or 370° and only 2-14% of this was recovered after treatment with receptor-destroying enzyme followed by freeze-thawing the cells. In contrast, high recoveries (36-112% of that adsorbed) were obtained from red blood cells that were treated similarly. Significant differences were not detected between the clones in either adsorption by or recovery from phagocytes of the different types of exudates. Thus pyrexia and the nasal inflammatory cells probably play a major role in the reduction of nasal tract infection but, while pyrexia may have had some influence, no evidence was obtained to indicate that the cells contributed to the earlier reduction of Clone 64d. PMID:607985

  1. Challenges to reestablishment of free-ranging populations of black-footed ferrets

    USGS Publications Warehouse

    Biggins, D.E.; Godbey, J.L.

    2003-01-01

    The black-footed ferret (Mustela nigripes) of North America is critically endangered due in part to its extreme specialization on formerly stable and abundant prairie dogs (Cynomys). Its close relative, the Siberian polecat (M. eversmannii) seems to have been subjected to a varying environment that was not conducive to specialization. One source of environmental variation in Asian steppes was plague (caused by Yersina pestis), which was absent from North America. Introduction of plague to North America presents serious challenges to ferret recovery. Partial solutions to other biological and political problems have been found, resulting in improved production in captivity, increased survival post-release, and thriving populations in plague-free South Dakota. ?? 2003 Acade??mie des sciences. Published by E??ditions scientifiques et me??dicales Elsevier SAS. All rights reserved.

  2. Mistuning detection performance of ferrets in a go/no-go task.

    PubMed

    Homma, Natsumi Y; Bajo, Victoria M; Happel, Max F K; Nodal, Fernando R; King, Andrew J

    2016-06-01

    The harmonic structure of sounds is an important grouping cue in auditory scene analysis. The ability of ferrets to detect mistuned harmonics was measured using a go/no-go task paradigm. Psychometric functions plotting sensitivity as a function of degree of mistuning were used to evaluate behavioral performance using signal detection theory. The mean (± standard error of the mean) threshold for mistuning detection was 0.8 ± 0.1 Hz, with sensitivity indices and reaction times depending on the degree of mistuning. These data provide a basis for investigation of the neural basis for the perception of complex sounds in ferrets, an increasingly used animal model in auditory research. PMID:27369180

  3. A case of advanced second-degree atrioventricular block in a ferret secondary to lymphoma

    PubMed Central

    Menicagli, F.; Lanza, A.; Sbrocca, F.; Baldi, A.; Spugnini, E.P.

    2016-01-01

    A female ferret was referred as an emergency for severe respiratory distress symptoms. At presentation, the patient was listlessness, dyspnoeic, and hyper-responsive. The clinical examination evidenced dyspnea with cyanosis, altered cardiac rhythm, and hepatomegaly. Electrocardiography showed an advanced second-degree atrioventricular (AV) block. The liver aspirate was diagnostic for lymphoma. The patient did not respond to supportive therapy and rapidly died. Post-mortem exams confirmed the presence of lymphoma with hepatic involvement. Moreover, a pericardial lymphocytic infiltration and a widespread myocardial nodular localization of lymphoma were evidenced as well. This condition was probably the cause of the cardiac arrhythmia. To the best of our knowledge, ours is the first report of cardiac lymphoma causing heart block in ferrets. PMID:27200273

  4. The Effects of Gamma and Proton Radiation Exposure on Hematopoietic Cell Counts in the Ferret Model.

    PubMed

    Sanzari, Jenine K; Wan, X Steven; Krigsfeld, Gabriel S; Wroe, Andrew J; Gridley, Daila S; Kennedy, Ann R

    2013-10-01

    Exposure to total-body radiation induces hematological changes, which can detriment one's immune response to wounds and infection. Here, the decreases in blood cell counts after acute radiation doses of γ-ray or proton radiation exposure, at the doses and dose-rates expected during a solar particle event (SPE), are reported in the ferret model system. Following the exposure to γ-ray or proton radiation, the ferret peripheral total white blood cell (WBC) and lymphocyte counts decreased whereas neutrophil count increased within 3 hours. At 48 hours after irradiation, the WBC, neutrophil, and lymphocyte counts decreased in a dose-dependent manner but were not significantly affected by the radiation type (γ-rays verses protons) or dose rate (0.5 Gy/minute verses 0.5 Gy/hour). The loss of these blood cells could accompany and contribute to the physiological symptoms of the acute radiation syndrome (ARS).

  5. Comparison of Digital Rectal and Microchip Transponder Thermometry in Ferrets (Mustela putorius furo).

    PubMed

    Maxwell, Branden M; Brunell, Marla K; Olsen, Cara H; Bentzel, David E

    2016-01-01

    Body temperature is a common physiologic parameter measured in both clinical and research settings, with rectal thermometry being implied as the 'gold standard.' However, rectal thermometry usually requires physical or chemical restraint, potentially causing falsely elevated readings due to animal stress. A less stressful method may eliminate this confounding variable. The current study compared 2 types of digital rectal thermometers-a calibrated digital thermometer and a common digital thermometer-with an implantable subcutaneous transponder microchip. Microchips were implanted subcutaneously between the shoulder blades of 16 ferrets (8 male, 8 female), and temperatures were measured twice from the microchip reader and once from each of the rectal thermometers. Results demonstrated the microchip temperature readings had very good to good correlation and agreement to those from both of the rectal thermometers. This study indicates that implantable temperature-sensing microchips are a reliable alternative to rectal thermometry for monitoring body temperature in ferrets.

  6. STUDIES ON THE NASAL HISTOLOGY OF EPIDEMIC INFLUENZA VIRUS INFECTION IN THE FERRET

    PubMed Central

    Francis, Thomas; Stuart-Harris, C. H.

    1938-01-01

    A study has been made of the nasal histology in normal ferrets and in ferrets during and after infection with epidemic influenza virus. During the acute stage of infection the respiratory epithelium of the nasal mucous membrane undergoes necrosis with desquamation of the superficial cells and exudation into the air passages, and an inflammatory reaction occurs in the submucosa. Repair begins on the 4th day after infection, and from the 6th to the 14th day the respiratory area is covered successively by a transitional, a stratified squamous, and finally a stratified columnar epithelium. By the 21st day after infection the epithelium has been largely restored to normal but repair in the submucosa and cartilage is still in progress. The respiratory mucosa is substantially normal in structure 1 month after infection although minor abnormalities of cellular arrangement and type can still be distinguished. PMID:19870817

  7. Comparison of Digital Rectal and Microchip Transponder Thermometry in Ferrets (Mustela putorius furo)

    PubMed Central

    Maxwell, Branden M; Brunell, Marla K; Olsen, Cara H; Bentzel, David E

    2016-01-01

    Body temperature is a common physiologic parameter measured in both clinical and research settings, with rectal thermometry being implied as the ‘gold standard.’ However, rectal thermometry usually requires physical or chemical restraint, potentially causing falsely elevated readings due to animal stress. A less stressful method may eliminate this confounding variable. The current study compared 2 types of digital rectal thermometers—a calibrated digital thermometer and a common digital thermometer—with an implantable subcutaneous transponder microchip. Microchips were implanted subcutaneously between the shoulder blades of 16 ferrets (8 male, 8 female), and temperatures were measured twice from the microchip reader and once from each of the rectal thermometers. Results demonstrated the microchip temperature readings had very good to good correlation and agreement to those from both of the rectal thermometers. This study indicates that implantable temperature-sensing microchips are a reliable alternative to rectal thermometry for monitoring body temperature in ferrets. PMID:27177569

  8. Comparison of Digital Rectal and Microchip Transponder Thermometry in Ferrets (Mustela putorius furo).

    PubMed

    Maxwell, Branden M; Brunell, Marla K; Olsen, Cara H; Bentzel, David E

    2016-01-01

    Body temperature is a common physiologic parameter measured in both clinical and research settings, with rectal thermometry being implied as the 'gold standard.' However, rectal thermometry usually requires physical or chemical restraint, potentially causing falsely elevated readings due to animal stress. A less stressful method may eliminate this confounding variable. The current study compared 2 types of digital rectal thermometers-a calibrated digital thermometer and a common digital thermometer-with an implantable subcutaneous transponder microchip. Microchips were implanted subcutaneously between the shoulder blades of 16 ferrets (8 male, 8 female), and temperatures were measured twice from the microchip reader and once from each of the rectal thermometers. Results demonstrated the microchip temperature readings had very good to good correlation and agreement to those from both of the rectal thermometers. This study indicates that implantable temperature-sensing microchips are a reliable alternative to rectal thermometry for monitoring body temperature in ferrets. PMID:27177569

  9. Exhaled aerosol transmission of pandemic and seasonal H1N1 influenza viruses in the ferret.

    PubMed

    Koster, Frederick; Gouveia, Kristine; Zhou, Yue; Lowery, Kristin; Russell, Robert; MacInnes, Heather; Pollock, Zemmie; Layton, R Colby; Cromwell, Jennifer; Toleno, Denise; Pyle, John; Zubelewicz, Michael; Harrod, Kevin; Sampath, Rangarajan; Hofstadler, Steven; Gao, Peng; Liu, Yushi; Cheng, Yung-Sung

    2012-01-01

    Person-to-person transmission of influenza viruses occurs by contact (direct and fomites) and non-contact (droplet and small particle aerosol) routes, but the quantitative dynamics and relative contributions of these routes are incompletely understood. The transmissibility of influenza strains estimated from secondary attack rates in closed human populations is confounded by large variations in population susceptibilities. An experimental method to phenotype strains for transmissibility in an animal model could provide relative efficiencies of transmission. We developed an experimental method to detect exhaled viral aerosol transmission between unanesthetized infected and susceptible ferrets, measured aerosol particle size and number, and quantified the viral genomic RNA in the exhaled aerosol. During brief 3-hour exposures to exhaled viral aerosols in airflow-controlled chambers, three strains of pandemic 2009 H1N1 strains were frequently transmitted to susceptible ferrets. In contrast one seasonal H1N1 strain was not transmitted in spite of higher levels of viral RNA in the exhaled aerosol. Among three pandemic strains, the two strains causing weight loss and illness in the intranasally infected 'donor' ferrets were transmitted less efficiently from the donor than the strain causing no detectable illness, suggesting that the mucosal inflammatory response may attenuate viable exhaled virus. Although exhaled viral RNA remained constant, transmission efficiency diminished from day 1 to day 5 after donor infection. Thus, aerosol transmission between ferrets may be dependent on at least four characteristics of virus-host relationships including the level of exhaled virus, infectious particle size, mucosal inflammation, and viral replication efficiency in susceptible mucosa.

  10. Reduced subventricular zone proliferation and white matter damage in juvenile ferrets with kaolin-induced hydrocephalus.

    PubMed

    Di Curzio, Domenico L; Buist, Richard J; Del Bigio, Marc R

    2013-10-01

    Hydrocephalus is a neurological condition characterized by altered cerebrospinal fluid (CSF) flow with enlargement of ventricular cavities in the brain. A reliable model of hydrocephalus in gyrencephalic mammals is necessary to test preclinical hypotheses. Our objective was to characterize the behavioral, structural, and histological changes in juvenile ferrets following induction of hydrocephalus. Fourteen-day old ferrets were given an injection of kaolin (aluminum silicate) into the cisterna magna. Two days later and repeated weekly until 56 days of age, magnetic resonance (MR) imaging was used to assess ventricle size. Behavior was examined thrice weekly. Compared to age-matched saline-injected controls, severely hydrocephalic ferrets weighed significantly less, their postures were impaired, and they were hyperactive prior to extreme debilitation. They developed significant ventriculomegaly and displayed white matter destruction. Reactive astroglia and microglia detected by glial fibrillary acidic protein (GFAP) and Iba-1 immunostaining were apparent in white matter, cortex, and hippocampus. There was a hydrocephalus-related increase in activated caspase 3 labeling of apoptotic cells (7.0 vs. 15.5%) and a reduction in Ki67 labeling of proliferating cells (23.3 vs. 5.9%) in the subventricular zone (SVZ). Reduced Olig2 immunolabeling suggests a depletion of glial precursors. GFAP content was elevated. Myelin basic protein (MBP) quantitation and myelin biochemical enzyme activity showed early maturational increases. Where white matter was not destroyed, the remaining axons developed myelin similar to the controls. In conclusion, the hydrocephalus-induced periventricular disturbances may involve developmental impairments in cell proliferation and glial precursor cell populations. The ferret should prove useful for testing hypotheses about white matter damage and protection in the immature hydrocephalic brain.

  11. Replication and Transmission of H9N2 Influenza Viruses in Ferrets: Evaluation of Pandemic Potential

    PubMed Central

    Song, Haichen; Hossain, Md Jaber; Ramirez-Nieto, Gloria; Monne, Isabella; Stevens, James; Cattoli, Giovanni; Capua, Ilaria; Chen, Li-Mei; Donis, Ruben O.; Busch, Julia; Paulson, James C.; Brockwell, Christy; Webby, Richard; Blanco, Jorge; Al-Natour, Mohammad Q.; Perez, Daniel R.

    2008-01-01

    H9N2 avian influenza A viruses are endemic in poultry of many Eurasian countries and have caused repeated human infections in Asia since 1998. To evaluate the potential threat of H9N2 viruses to humans, we investigated the replication and transmission efficiency of H9N2 viruses in the ferret model. Five wild-type (WT) H9N2 viruses, isolated from different avian species from 1988 through 2003, were tested in vivo and found to replicate in ferrets. However these viruses achieved mild peak viral titers in nasal washes when compared to those observed with a human H3N2 virus. Two of these H9N2 viruses transmitted to direct contact ferrets, however no aerosol transmission was detected in the virus displaying the most efficient direct contact transmission. A leucine (Leu) residue at amino acid position 226 in the hemagglutinin (HA) receptor-binding site (RBS), responsible for human virus-like receptor specificity, was found to be important for the transmission of the H9N2 viruses in ferrets. In addition, an H9N2 avian-human reassortant virus, which contains the surface glycoprotein genes from an H9N2 virus and the six internal genes of a human H3N2 virus, showed enhanced replication and efficient transmission to direct contacts. Although no aerosol transmission was observed, the virus replicated in multiple respiratory tissues and induced clinical signs similar to those observed with the parental human H3N2 virus. Our results suggest that the establishment and prevalence of H9N2 viruses in poultry pose a significant threat for humans. PMID:18698430

  12. Focal thoracolumbar spinal cord lymphosarcoma in a ferret (Mustela putorius furo)

    PubMed Central

    Ingrao, Joelle C.; Eshar, David; Vince, Andrew; Lee-Chow, Bridget; Nykamp, Stephanie; DeLay, Josepha; Smith, Dale

    2014-01-01

    A 6-year-old, castrated male domestic ferret (Mustela putorius furo) was euthanized following progressive hind limb paresis and atonia of the bladder of 1-year duration. Neurological evaluation localized the lesion to the thoracolumbar spinal region, and magnetic resonance imaging showed a focal intramedullary spinal cord lesion. Histopathology revealed an extensive, unencapsulated, poorly demarcated mass within the thoracolumbar spinal cord, diagnosed as lymphosarcoma. PMID:24982519

  13. Metastatic, papillary cystadenocarcinoma of the mammary gland in a black-footed ferret

    USGS Publications Warehouse

    Carpenter, J.W.; Davidson, J.P.; Novilla, M.N.; Huang, J.C.M.

    1980-01-01

    A simple, papillary cystic adenocarcinoma of the mammary gland with metastases to the internal iliac and mesenteric lymph nodes, liver, and spleen was observed in a 12 to 13 year old female black-footed ferret (Mustela nigripes). Histologically, the tumor was aggressive, and lymphatic invasion was found. Attempts at virus isolation were negative. Other findings were bilateral infarcts in the kidneys, apparently resulting in acute renal shutdown and death, multiple thrombi in the right atrium, aortic arteriosclerosis, and focal interstitial pneumonia.

  14. Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets

    PubMed Central

    Herfst, Sander; Bodewes, Rogier; Pfankuche, Vanessa M.; van de Bildt, Marco W. G.; Seehusen, Frauke; Puff, Christina; Richard, Mathilde; Siebert, Ursula; Lehnert, Kristina; Bestebroer, Theo; Lexmond, Pascal; Fouchier, Ron A. M.; Prenger-Berninghoff, Ellen; Herbst, Werner; Koopmans, Marion; Osterhaus, Albert D. M. E.

    2016-01-01

    Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans

  15. Ferretting out the facts behind the H5N1 controversy

    PubMed Central

    2012-01-01

    Recent recommendations by the National Science Advisory Board for Biosecurity (NSABB) to redact key methodological details of two studies involving mammal-to-mammal transmission of the H5N1 (H5) subtype influenza viruses, has led to a temporary moratorium on all research involving live H5N1 or H5 HA reassortant viruses shown to be transmissible in ferrets. Herein, I review the events which led to this impasse and comment on their impact. PMID:22402712

  16. Influenza A (H10N7) Virus Causes Respiratory Tract Disease in Harbor Seals and Ferrets.

    PubMed

    van den Brand, Judith M A; Wohlsein, Peter; Herfst, Sander; Bodewes, Rogier; Pfankuche, Vanessa M; van de Bildt, Marco W G; Seehusen, Frauke; Puff, Christina; Richard, Mathilde; Siebert, Ursula; Lehnert, Kristina; Bestebroer, Theo; Lexmond, Pascal; Fouchier, Ron A M; Prenger-Berninghoff, Ellen; Herbst, Werner; Koopmans, Marion; Osterhaus, Albert D M E; Kuiken, Thijs; Baumgärtner, Wolfgang

    2016-01-01

    Avian influenza viruses sporadically cross the species barrier to mammals, including humans, in which they may cause epidemic disease. Recently such an epidemic occurred due to the emergence of avian influenza virus of the subtype H10N7 (Seal/H10N7) in harbor seals (Phoca vitulina). This epidemic caused high mortality in seals along the north-west coast of Europe and represented a potential risk for human health. To characterize the spectrum of lesions and to identify the target cells and viral distribution, findings in 16 harbor seals spontaneously infected with Seal/H10N7 are described. The seals had respiratory tract inflammation extending from the nasal cavity to bronchi associated with intralesional virus antigen in respiratory epithelial cells. Virus infection was restricted to the respiratory tract. The fatal outcome of the viral infection in seals was most likely caused by secondary bacterial infections. To investigate the pathogenic potential of H10N7 infection for humans, we inoculated the seal virus intratracheally into six ferrets and performed pathological and virological analyses at 3 and 7 days post inoculation. These experimentally inoculated ferrets displayed mild clinical signs, virus excretion from the pharynx and respiratory tract inflammation extending from bronchi to alveoli that was associated with virus antigen expression exclusively in the respiratory epithelium. Virus was isolated only from the respiratory tract. In conclusion, Seal/H10N7 infection in naturally infected harbor seals and experimentally infected ferrets shows that respiratory epithelial cells are the permissive cells for viral replication. Fatal outcome in seals was caused by secondary bacterial pneumonia similar to that in fatal human cases during influenza pandemics. Productive infection of ferrets indicates that seal/H10N7 may possess a zoonotic potential. This outbreak of LPAI from wild birds to seals demonstrates the risk of such occasions for mammals and thus humans

  17. Characterization of neural control and contractile function in airway smooth muscle of the ferret.

    PubMed

    Maize, D F; Fedan, J S; Dey, R D

    1998-02-01

    Several recent studies have characterized neuroanatomical and neurophysiological aspects of ferret airways, but regional differences in reactivity and cholinergic, adrenergic and non-adrenergic-non-cholinergic (NANC) neural responses have not been examined. The aim of this study was to characterize the contractile and relaxant response elicited by electrical field stimulation (EFS), and the contractions induced by cholinergic agonists in isolated ferret tracheal and bronchial preparations. EFS produced frequency-dependent contractions and relaxations. Contractions in both the trachea and bronchi were inhibited by atropine and potentiated by neostigmine. Tracheal relaxations were found to be entirely adrenergic, but bronchial relaxations were mediated by a combination of adrenergic and inhibitory NANC (i-NANC) innervations. Trachea and bronchi were more sensitive to methacholine (MCh) and carbachol than to acetylcholine (ACh); middle tracheal segments being more sensitive to ACh than distal segments, however, in the presence of neostigmine ACh potency was equal in both segments. The results suggest that regional differences exist in cholinergic responsiveness of ferret trachea and bronchi, resulting from differences in ACh degradation.

  18. Male prevalent enhancement of leftward asymmetric development of the cerebellar cortex in ferrets (Mustela putorius).

    PubMed

    Sawada, Kazuhiko; Horiuchi-Hirose, Miwa; Saito, Shigeyoshi; Aoki, Ichio

    2015-01-01

    The present study was conducted in MRI-based volumetry to characterize the sexual dimorphism of the cerebellum in young adult ferrets. High spatial resolution 3D anatomical MRI at 7-tesla were acquired ex vivo from fixed cerebella of 90-day-old male and female ferrets. The 3D morphology and topology of cerebellar structures were reproduced well by volume-rendered images obtained from MRI. Volume of the whole cerebellum was significantly larger in males than in females. The cerebellar cortex was further divided into five transverse domains: the anterior zone (AZ; lobules I-V), central zone anterior (lobule VI), central zone posterior (CZp; lobule VII), posterior zone (PZ; lobules VIII-IXa) and nodular zone (NZ; lobules IXb -X). Significantly greater volumes in males than in females were detected bilaterally in the AZ, CZp, and NZ, and leftward in PZ. Notably, the significant volume asymmetry was detected leftward in the CZp of males. By asymmetry quotient analysis, the counterclockwise torque asymmetry of the cerebellum was revealed, and it was more striking in males than in females. The present results suggest that sexual dimorphism of the ferret cerebellum is characterized by enhancing the leftward laterality in the CZp in males, forming the distinctive counterclockwise torque asymmetry. PMID:26102223

  19. Factors affecting the efficiency of embryo transfer in the domestic ferret (Mustela putorius furo)

    PubMed Central

    Li, Ziyi; Sun, Xingshen; Chen, Juan; Leno, Gregory H.; Engelhardt, John F.

    2007-01-01

    Embryo transfer (ET) to recipient females is a foundational strategy for a number of assisted reproductive technologies, including cloning by somatic cell nuclear transfer. In an attempt to develop efficient ET in domestic ferrets, factors affecting development of transferred embryo were investigated. Unilateral and bilateral transfer of zygotes or blastocysts in the oviduct or uterus was evaluated in recipient nulliparous or primiparous females. Developing fetuses were collected from recipient animals 21 days post-copulation and examined. The percentage of fetal formation was different (P < 0.05) for unilateral and bilateral transfer of zygotes (71%) in nulliparous females with bilateral transfer (56%) in primiparous recipients. The percentage (90%) of fetal formation in nulliparous recipients following unilateral transfer of blastocysts was higher (P < 0.05) than that observed in primiparous recipients with bilateral ET (73%). Notably, the percentage of fetal formation was higher (P < 0.05) when blastocyts were transferred as compared to zygotes (90% versus 71%). Transuterine migration of embryos occurred following all unilateral transfers and also in approximately 50% of bilateral transfers with different number of embryos in each uterine horn. These data will help to facilitate the development of assisted reproductive strategies in the ferret and could lead to the use of this species for modeling human disease and for conservation of the endangered Mustelidae species such as black-footed ferret and European mink. PMID:16330092

  20. Factors affecting the efficiency of embryo transfer in the domestic ferret (Mustela putorius furo).

    PubMed

    Li, Ziyi; Sun, Xingshen; Chen, Juan; Leno, Gregory H; Engelhardt, John F

    2006-07-15

    Embryo transfer (ET) to recipient females is a foundational strategy for a number of assisted reproductive technologies, including cloning by somatic cell nuclear transfer. In an attempt to develop efficient ET in domestic ferrets, factors affecting development of transferred embryo were investigated. Unilateral and bilateral transfer of zygotes or blastocysts in the oviduct or uterus was evaluated in recipient nulliparous or primiparous females. Developing fetuses were collected from recipient animals 21 days post-copulation and examined. The percentage of fetal formation was different (P<0.05) for unilateral and bilateral transfer of zygotes (71%) in nulliparous females with bilateral transfer (56%) in primiparous recipients. The percentage (90%) of fetal formation in nulliparous recipients following unilateral transfer of blastocysts was higher (P<0.05) than that observed in primiparous recipients with bilateral ET (73%). Notably, the percentage of fetal formation was higher (P<0.05) when blastocyts were transferred as compared to zygotes (90% versus 71%). Transuterine migration of embryos occurred following all unilateral transfers and also in approximately 50% of bilateral transfers with different number of embryos in each uterine horn. These data will help to facilitate the development of assisted reproductive strategies in the ferret and could lead to the use of this species for modeling human disease and for conservation of the endangered Mustelidae species such as black-footed ferret and European mink. PMID:16330092

  1. Visualizing real-time influenza virus infection, transmission and protection in ferrets

    PubMed Central

    Karlsson, Erik A.; Meliopoulos, Victoria A.; Savage, Chandra; Livingston, Brandi; Mehle, Andrew; Schultz-Cherry, Stacey

    2015-01-01

    Influenza transmission efficiency in ferrets is vital for risk-assessment studies. However, the inability to monitor viral infection and transmission dynamics in real time only provides a glimpse into transmissibility. Here we exploit a replication-competent influenza reporter virus to investigate dynamics of infection/transmission in ferrets. Bioluminescent imaging of ferrets infected with A/California/04/2009 H1N1 virus (CA/09) encoding NanoLuc (NLuc) luciferase provides the first real-time snapshot of influenza infection/transmission. Luminescence in the respiratory tract and in less well-characterized extra-pulmonary sites is observed, and imaging identifies infections in animals that would have otherwise been missed by traditional methods. Finally, the reporter virus significantly increases the speed and sensitivity of virological and serological assays. Thus, bioluminescent imaging of influenza infections rapidly determines intra-host dissemination, inter-host transmission and viral load, revealing infection dynamics and pandemic potential of the virus. These results have important implications for antiviral drug susceptibility, vaccine efficacy, transmissibility and pathogenicity studies. PMID:25744559

  2. Variation of the ferret skull (Mustela putorius furo L.) in relation to stereotaxic landmarks.

    PubMed Central

    Lawes, I N; Andrews, P L

    1987-01-01

    The ferret skull was investigated to identify reliable extracranial landmarks for stereotaxy. The skulls of 56 ferrets of both sexes were measured in a stereotaxic apparatus. Neither body weight nor an index of skull length proved to be reliable predictors of intracranial location. Sutures fused too early in life for lambda and bregma to be useful as landmarks in adult ferrets. The position of extracranial features was used to predict the position of intracranial features. For rostral intracranial features, the supraorbital processes were found to be the best predictors. Although the occipital crest was not the best predictor for posterior structures, it was the most practical. Using these landmarks, the prediction of intracranial location could be improved by more than 30%. Sexual dimorphism was found for all features examined except those nearest the interaural line. Female skulls were significantly smaller than male skulls and had less prominent sagittal and occipital crests. Males showed a substantial variation in the structures surrounding the pituitary gland. Fitches were also found to differ from albinos in having a more marked development of the sagittal crest. Images Fig. 1 Fig. 2 PMID:3328744

  3. Implications of black-tailed prairie dog spatial dynamics to black-footed ferrets

    USGS Publications Warehouse

    Jachowski, D.S.; Millspaugh, J.J.; Biggins, D.E.; Livieri, T.M.; Matchett, M.R.

    2008-01-01

    The spatial dynamics of black-tailed prairie dog (Cynomys ludovicianus) colonies affect the utility of these environments for other wildlife, including the endangered black-footed ferret (Mustela nigripes). We used location data of active and inactive black-tailed prairie dog burrows to investigate colony structure, spatial distribution, and patch dynamics of two colonies at ferret recovery sites. We used kernel-based utilization distributions (UDs) of active and inactive burrows from two time periods (six and 11 years apart) as the basis for our analysis. Overall, the total extent of our prairie dog colonies changed little over time. However, within colonies, areas with high densities of active and inactive prairie dog burrows formed patches and the distribution of these patches changed in size, shape, and connectivity over time. At the Conata Basin site, high-density active burrow patches increased in total area covered while decreasing in connectivity as they shifted towards the perimeter of the colony over time. At the UL Bend site, we observed a similar but less pronounced shift over a longer period of time. At both sites, while at a large scale it appeared that prairie dogs were simply shifting areas of activity towards the perimeter of colonies and abandoning the center of colonies, we observed a dynamic interaction between areas of active and inactive burrows within colonies over time. Areas that previously contained inactive burrows tended to become active, and vice versa, leading us to hypothesize that there are shifts of activity areas within colonies over time as dictated by forage availability. The spatial dynamics we observed have important implications for techniques to estimate the suitability of ferret habitat and for the management of prairie dog colonies. First, fine-scale techniques for measuring prairie dog colonies that account for their patchy spatial distribution are needed to better assess ferret habitat suitability. Second, the shift of

  4. Impact of Adjuvants on the Immunogenicity and Efficacy of Split-Virion H7N9 Vaccine in Ferrets

    PubMed Central

    Wong, Sook-San; Kaplan, Bryan; Zanin, Mark; Debeauchamp, Jennifer; Kercher, Lisa; Crumpton, Jeri-Carol; Seiler, Patrick; Sun, Yilun; Tang, Li; Krauss, Scott; Webster, Robert; Webby, Richard J.

    2015-01-01

    Background. An effective vaccine is urgently needed against the H7N9 avian influenza virus. We evaluated the immunogenicity and protective efficacy of a split-virion H7N9 vaccine with or without the oil-in-water adjuvants in ferrets. Methods. Ferrets were vaccinated with 2 doses of unadjuvanted, MF59 or AS03-adjuvanted A/Shanghai/2/2013 (H7N9) vaccine, and the induction of antibodies to hemagglutinin (HA) or neuraminidase proteins was evaluated. Ferrets were then challenged with wild-type H7N9 virus to assess the vaccine's protective efficacy. The vaccine composition and integrity was also evaluated in vitro. Results. Adjuvanted vaccines stimulated robust serum antibody titers against HA and neuraminidase compared with the unadjuvanted vaccines. Although there was a difference in adjuvanticity between AS03 and MF59 at a lower dose (3.75 µg of HA), both adjuvants induced comparable antibody responses after 2 doses of 15 µg. On challenge, ferrets that received adjuvanted vaccines showed lower viral burden than the control or unadjuvanted vaccine group. In vitro examinations revealed that the vaccine contained visible split-virus particles and retained the native conformation of HA recognizable by polyclonal and monoclonal antibodies. Conclusions. The adjuvanted H7N9 vaccines demonstrated superior immunogenicity and protective efficacy against H7N9 infection in ferrets and hold potential as a vaccination regimen. PMID:25712975

  5. H7N9 Influenza Virus Is More Virulent in Ferrets than 2009 Pandemic H1N1 Influenza Virus.

    PubMed

    Yum, Jung; Ku, Keun Bon; Kim, Hyun Soo; Seo, Sang Heui

    2015-12-01

    The novel H7N9 influenza virus has been infecting humans in China since February 2013 and with a mortality rate of about 40%. This study compared the pathogenicity of the H7N9 and 2009 pandemic H1N1 influenza viruses in a ferret model, which shows similar symptoms to those of humans infected with influenza viruses. The H7N9 influenza virus caused a more severe disease than did the 2009 pandemic H1N1 influenza virus. All of the ferrets infected with the H7N9 influenza virus had died by 6 days after infection, while none of those infected with the 2009 pandemic H1N1 influenza virus died. Ferrets infected with the H7N9 influenza virus had higher viral titers in their lungs than did those infected with the 2009 pandemic H1N1 influenza virus. Histological findings indicated that hemorrhagic pneumonia was caused by infection with the H7N9 influenza virus, but not with the 2009 pandemic H1N1 influenza virus. In addition, the lung tissues of ferrets infected with the H7N9 influenza virus contained higher levels of chemokines than did those of ferrets infected with the 2009 pandemic H1N1 influenza virus. This study suggests that close monitoring is needed to prevent human infection by the lethal H7N9 influenza virus.

  6. Mouse adaptation of influenza B virus increases replication in the upper respiratory tract and results in droplet transmissibility in ferrets.

    PubMed

    Kim, Eun-Ha; Park, Su-Jin; Kwon, Hyeok-Il; Kim, Se Mi; Kim, Young-il; Song, Min-Suk; Choi, Eun-Ji; Pascua, Philippe Noriel Q; Choi, Young-Ki

    2015-01-01

    To investigate the molecular changes that allow influenza B viruses to adapt to new mammalian hosts, influenza B/Florida/04/2006 was serially passaged in BALB/c mice until highly virulent. The viral factors underlying this transition were then investigated in mice and ferrets. Five viruses, including the wild-type virus (P0), three intermediate viruses (P5, P9, and P12), and a lethal mouse-adapted virus (P17 (MA)), harbored one to five amino acid substitutions in the hemagglutinin, M, NP, and PA segments suggesting that these mutations enhance virulence. The P17 (MA) virus replicated significantly more efficiently than the P0 virus both in vitro and in vivo (P < 0.0001), and was highly virulent (MLD50: 10(5.25)TCID50) while the P0, P5, and P9 viruses did not kill any infected mice (MLD50 > 10(6.0)TCID50). Furthermore, the P17 (MA) virus grew to greater titers in the ferret upper respiratory tract compared with the P0 and intermediate viruses, and only the P17 (MA) virus was transmissible between ferrets via both direct and aerosol contact. To our knowledge, this is the first study to demonstrate ferret-to-ferret transmission of influenza B virus and to delineate factors that may affect its transmission. PMID:26526113

  7. Mouse adaptation of influenza B virus increases replication in the upper respiratory tract and results in droplet transmissibility in ferrets

    PubMed Central

    Kim, Eun-Ha; Park, Su-Jin; Kwon, Hyeok-Il; Kim, Se Mi; Kim, Young-il; Song, Min-Suk; Choi, Eun-Ji; Pascua, Philippe Noriel Q.; Choi, Young-Ki

    2015-01-01

    To investigate the molecular changes that allow influenza B viruses to adapt to new mammalian hosts, influenza B/Florida/04/2006 was serially passaged in BALB/c mice until highly virulent. The viral factors underlying this transition were then investigated in mice and ferrets. Five viruses, including the wild-type virus (P0), three intermediate viruses (P5, P9, and P12), and a lethal mouse-adapted virus (P17 (MA)), harbored one to five amino acid substitutions in the hemagglutinin, M, NP, and PA segments suggesting that these mutations enhance virulence. The P17 (MA) virus replicated significantly more efficiently than the P0 virus both in vitro and in vivo (P < 0.0001), and was highly virulent (MLD50: 105.25TCID50) while the P0, P5, and P9 viruses did not kill any infected mice (MLD50 > 106.0TCID50). Furthermore, the P17 (MA) virus grew to greater titers in the ferret upper respiratory tract compared with the P0 and intermediate viruses, and only the P17 (MA) virus was transmissible between ferrets via both direct and aerosol contact. To our knowledge, this is the first study to demonstrate ferret-to-ferret transmission of influenza B virus and to delineate factors that may affect its transmission. PMID:26526113

  8. Neutralizing inhibitors in the airways of naïve ferrets do not play a major role in modulating the virulence of H3 subtype influenza A viruses.

    PubMed

    Job, Emma R; Pizzolla, Angela; Nebl, Thomas; Short, Kirsty R; Deng, Yi-Mo; Carolan, Louise; Laurie, Karen L; Brooks, Andrew G; Reading, Patrick C

    2016-07-01

    Many insights regarding the pathogenesis of human influenza A virus (IAV) infections have come from studies in mice and ferrets. Surfactant protein (SP)-D is the major neutralizing inhibitor of IAV in mouse airway fluids and SP-D-resistant IAV mutants show enhanced virus replication and virulence in mice. Herein, we demonstrate that sialylated glycoproteins, rather than SP-D, represent the major neutralizing inhibitors against H3 subtype viruses in airway fluids from naïve ferrets. Moreover, while resistance to neutralizing inhibitors is a critical factor in modulating virus replication and disease in the mouse model, it does not appear to be so in the ferret model, as H3 mutants resistant to either SP-D or sialylated glycoproteins in ferret airway fluids did not show enhanced virulence in ferrets. These data have important implications for our understanding of pathogenesis and immunity to human IAV infections in these two widely used animal models of infection. PMID:27110707

  9. Prenatal and neonatal testosterone exposure interact to affect differentiation of sexual behavior and partner preference in female ferrets.

    PubMed

    Baum, M J; Erskine, M S; Kornberg, E; Weaver, C E

    1990-02-01

    Implanting testosterone (T) subcutaneously over Postnatal Days 5-20 masculinized sexual behavior, reduced proceptive responsiveness, and shifted sexual preference more readily in male than in female ferrets gonadectomized on Day 5. This enhanced sensitivity of males to neonatal T was best duplicated in females exposed transplacentally to T over Embryonic Days (E) 27-39 (41-day gestation) and injected at birth with T (2.5 micrograms sc in oil: 10% ethanol). Extended exposure of male ferrets to high levels of T, beginning shortly after the onset of testicular steroidogenesis (E25) and continuing for several hours after birth (E41) normally sensitizes their brains to the subsequent organizational effects on coital performance and sexual motivation of the relatively low levels of T that circulate in male ferrets during the first 3 postnatal weeks.

  10. Efficacy of Oseltamivir Therapy in Ferrets Inoculated with Different Clades of H5N1 Influenza Virus▿

    PubMed Central

    Govorkova, Elena A.; Ilyushina, Natalia A.; Boltz, David A.; Douglas, Alan; Yilmaz, Neziha; Webster, Robert G.

    2007-01-01

    Highly pathogenic H5N1 influenza viruses have infected an increasing number of humans in Asia, with high mortality rates and the emergence of multiple distinguishable clades. It is not known whether antiviral drugs that are effective against contemporary human influenza viruses will be effective against systemically replicating viruses, such as these pathogens. Therefore, we evaluated the use of the neuraminidase (NA) inhibitor oseltamivir for early postexposure prophylaxis and for treatment in ferrets exposed to representatives of two clades of H5N1 virus with markedly different pathogenicities in ferrets. Ferrets were protected from lethal infection with the A/Vietnam/1203/04 (H5N1) virus by oseltamivir (5 mg/kg of body weight/day) given 4 h after virus inoculation, but higher daily doses (25 mg/kg) were required for treatment when it was initiated 24 h after virus inoculation. For the treatment of ferrets inoculated with the less pathogenic A/Turkey/15/06 (H5N1) virus, 10 mg/kg/day of oseltamivir was sufficient to reduce the lethargy of the animals, significantly inhibit inflammation in the upper respiratory tract, and block virus spread to the internal organs. Importantly, all ferrets that survived the initial infection were rechallenged with homologous virus after 21 days and were completely protected from infection. Direct sequencing of the NA or HA1 gene segments in viruses isolated from ferret after treatment showed no amino acid substitutions known to cause drug resistance in conserved residues. Thus, early oseltamivir treatment is crucial for protection against highly pathogenic H5N1 viruses and the higher dose may be needed for the treatment of more virulent viruses. PMID:17296744

  11. Severity of Clinical Disease and Pathology in Ferrets Experimentally Infected with Influenza Viruses Is Influenced by Inoculum Volume

    PubMed Central

    Moore, Ian N.; Lamirande, Elaine W.; Paskel, Myeisha; Donahue, Danielle; Qin, Jing

    2014-01-01

    ABSTRACT Ferrets are a valuable model for influenza virus pathogenesis, virus transmission, and antiviral therapy studies. However, the contributions of the volume of inoculum administered and the ferret's respiratory tract anatomy to disease outcome have not been explored. We noted variations in clinical disease outcomes and the volume of inoculum administered and investigated these differences by administering two influenza viruses (A/California/07/2009 [H1N1 pandemic] and A/Minnesota/11/2010 [H3N2 variant]) to ferrets intranasally at a dose of 106 50% tissue culture infective doses in a range of inoculum volumes (0.2, 0.5, or 1.0 ml) and followed viral replication, clinical disease, and pathology over 6 days. Clinical illness and respiratory tract pathology were the most severe and most consistent when the viruses were administered in a volume of 1.0 ml. Using a modified micro-computed tomography imaging method and examining gross specimens, we found that the right main-stem bronchus was consistently larger in diameter than the left main-stem bronchus, though the latter was longer and straighter. These anatomic features likely influence the distribution of the inoculum in the lower respiratory tract. A 1.0-ml volume of inoculum is optimal for delivery of virus to the lower respiratory tract of ferrets, particularly when evaluation of clinical disease is desired. Furthermore, we highlight important anatomical features of the ferret lung that influence the kinetics of viral replication, clinical disease severity, and lung pathology. IMPORTANCE Ferrets are a valuable model for influenza virus pathogenesis, virus transmission, and antiviral therapy studies. Clinical disease in ferrets is an important parameter in evaluating the virulence of novel influenza viruses, and findings are extrapolated to virulence in humans. Therefore, it is highly desirable that the data from different laboratories be accurate and reproducible. We have found that, even when the same virus

  12. Effects of developmental alcohol and valproic acid exposure on play behavior of ferrets.

    PubMed

    Krahe, Thomas E; Filgueiras, Claudio C; Medina, Alexandre E

    2016-08-01

    Exposure to alcohol and valproic acid (VPA) during pregnancy can lead to fetal alcohol spectrum disorders and fetal valproate syndrome, respectively. Altered social behavior is a hallmark of both these conditions and there is ample evidence showing that developmental exposure to alcohol and VPA affect social behavior in rodents. However, results from rodent models are somewhat difficult to translate to humans owing to the substantial differences in brain development, morphology, and connectivity. Since the cortex folding pattern is closely related to its specialization and that social behavior is strongly influenced by cortical structures, here we studied the effects of developmental alcohol and VPA exposure on the play behavior of the ferret, a gyrencephalic animal known for its playful nature. Animals were injected with alcohol (3.5g/kg, i.p.), VPA (200mg/kg, i.p.) or saline (i.p) every other day during the brain growth spurt period, between postnatal days 10 and 30. The play behavior of pairs of the same experimental group was evaluated 3 weeks later. Both treatments induced significant behavioral differences compared to controls. Alcohol and VPA exposed ferrets played less than saline treated ones, but while animals from the alcohol group displayed a delay in start playing with each other, VPA treated ones spent most of the time close to one another without playing. These findings not only extend previous results on the effects of developmental exposure to alcohol and VPA on social behavior, but make the ferret a great model to study the underlying mechanisms of social interaction. PMID:27208641

  13. Avian influenza h6 viruses productively infect and cause illness in mice and ferrets.

    PubMed

    Gillim-Ross, Laura; Santos, Celia; Chen, Zhongying; Aspelund, Amy; Yang, Chin-Fen; Ye, Dan; Jin, Hong; Kemble, George; Subbarao, Kanta

    2008-11-01

    Influenza pandemic preparedness has focused on influenza virus H5 and H7 subtypes. However, it is not possible to predict with certainty which subtype of avian influenza virus will cause the next pandemic, and it is prudent to include other avian influenza virus subtypes in pandemic preparedness efforts. An H6 influenza virus was identified as a potential progenitor of the H5N1 viruses that emerged in Hong Kong in 1997. This virus continues to circulate in the bird population in Asia, and other H6 viruses are prevalent in birds in North America and Asia. The high rate of reassortment observed in influenza viruses and the prevalence of H6 viruses in birds suggest that this subtype may pose a pandemic risk. Very little is known about the replicative capacity, immunogenicity, and correlates of protective immunity for low-pathogenicity H6 influenza viruses in mammals. We evaluated the antigenic and genetic relatedness of 14 H6 influenza viruses and their abilities to replicate and induce a cross-reactive immune response in two animal models: mice and ferrets. The different H6 viruses replicated to different levels in the respiratory tracts of mice and ferrets, causing varied degrees of morbidity and mortality in these two models. H6 virus infection induced similar patterns of neutralizing antibody responses in mice and ferrets; however, species-specific differences in the cross-reactivity of the antibody responses were observed. Overall, cross-reactivity of neutralizing antibodies in H6 virus-infected mice did not correlate well with protection against heterologous wild-type H6 viruses. However, we have identified an H6 virus that induces protective immunity against viruses in the North American and Eurasian lineages.

  14. Pathogenicity and Transmissibility of North American Triple Reassortant Swine Influenza A Viruses in Ferrets

    PubMed Central

    Barman, Subrata; Krylov, Petr S.; Fabrizio, Thomas P.; Franks, John; Turner, Jasmine C.; Seiler, Patrick; Wang, David; Rehg, Jerold E.; Erickson, Gene A.; Gramer, Marie; Webster, Robert G.; Webby, Richard J.

    2012-01-01

    North American triple reassortant swine (TRS) influenza A viruses have caused sporadic human infections since 2005, but human-to-human transmission has not been documented. These viruses have six gene segments (PB2, PB1, PA, HA, NP, and NS) closely related to those of the 2009 H1N1 pandemic viruses. Therefore, understanding of these viruses' pathogenicity and transmissibility may help to identify determinants of virulence of the 2009 H1N1 pandemic viruses and to elucidate potential human health threats posed by the TRS viruses. Here we evaluated in a ferret model the pathogenicity and transmissibility of three groups of North American TRS viruses containing swine-like and/or human-like HA and NA gene segments. The study was designed only to detect informative and significant patterns in the transmissibility and pathogenicity of these three groups of viruses. We observed that irrespective of their HA and NA lineages, the TRS viruses were moderately pathogenic in ferrets and grew efficiently in both the upper and lower respiratory tracts. All North American TRS viruses studied were transmitted between ferrets via direct contact. However, their transmissibility by respiratory droplets was related to their HA and NA lineages: TRS viruses with human-like HA and NA were transmitted most efficiently, those with swine-like HA and NA were transmitted minimally or not transmitted, and those with swine-like HA and human-like NA (N2) showed intermediate transmissibility. We conclude that the lineages of HA and NA may play a crucial role in the respiratory droplet transmissibility of these viruses. These findings have important implications for pandemic planning and warrant confirmation. PMID:22829764

  15. Regulation of brain androgen receptor immunoreactivity by androgen in prepubertal male ferrets.

    PubMed

    Kashon, M L; Hayes, M J; Shek, P P; Sisk, C L

    1995-05-01

    During pubertal maturation, there is an increase in the number of androgen receptor-immunoreactive (AR-IR) cells in the preoptic area (POA), arcuate nucleus (ARC), medial amygdala (mAMY), and ventromedial hypothalamic nucleus (VMH) of the male ferret brain. In contrast, the number of AR-IR cells in the bed nucleus of the stria terminalis (BNST) or lateral septum (ISEP) does not change with pubertal development. This experiment tested the hypothesis that the pubertal increase in AR-IR cells in certain brain regions is the result of the pubertal increase in circulating androgens. Prepubertal male ferrets were left intact or were castrated and treated daily (10 days) with s.c. injections of either oil, testosterone (T; 5 mg/kg), dihydrotestosterone (DHT; 5 mg/kg), or estradiol (E; 10 micrograms/kg). Brains were processed for AR immunocytochemistry, and the number of immunopositive cells was quantified in POA, ARC, mAMY, VMH, BNST, and ISEP. Overall, castration reduced the number of AR-IR cells below that seen in intact animals, and E administration did not restore AR-IR cell number. Treatment of castrates with androgens restored numbers of AR-IR cells to those of intact animals in the BNST, ISEP, and VMH. However, AR-IR cell numbers were significantly greater in androgen-treated castrates than in intact animals in POA, mAMY, and ARC. These data show that AR-IR cells in prepubertal male ferrets are sensitive to circulating levels of androgens, supporting the hypothesis that the pubertal rise in T is responsible for the pubertal increase in the number of AR-IR cells in the POA, mAMY, and ARC. PMID:7626721

  16. Quantitative MRI and DTI Abnormalities During the Acute Period Following CCI in the Ferret

    PubMed Central

    Hutchinson, Elizabeth B.; Schwerin, Susan C.; Radomski, Kryslaine L.; Irfanoglu, Mustafa O.; Juliano, Sharon L.; Pierpaoli, Carlo M.

    2016-01-01

    Abstract During the acute time period following traumatic brain injury (TBI), noninvasive brain imaging tools such as magnetic resonance imaging (MRI) can provide important information about the clinical and pathological features of the injury and may help predict long-term outcomes. In addition to standard imaging approaches, several quantitative MRI techniques including relaxometry and diffusion MRI have been identified as promising reporters of cellular alterations after TBI and may provide greater sensitivity and specificity for identifying brain abnormalities especially in mild TBI. However, for these imaging tools to be useful, it is crucial to define their relationship with the neurophysiological response to brain injury. Recently, a model of controlled cortical impact (CCI) has been developed in the ferret which has many advantages compared with rodent models (e.g., gyrencephalic cortex and high white matter volume). The objective of this study was to evaluate quantitative MRI metrics in the ferret CCI model, including T2 values and diffusion tensor imaging (DTI) metrics, during the acute time period. Longitudinal quantitative comparisons of in vivo MRI and DTI metrics were evaluated to identify abnormalities and characterize their spatial patterns in the ferret brain. Ex vivo MRI and DTI maps were then compared with histological staining for glial and neuronal abnormalities. The main findings of this article describe T2, diffusivity, and anisotropy markers of tissue change during the acute time period following mild TBI, and ex vivo analyses suggest that MRI and DTI markers are sensitive to subtle cellular alterations in this model. This was confirmed by comparison with immunohistochemistry, also showing altered markers in regions of MRI and DTI change. PMID:27294688

  17. The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus

    PubMed Central

    Cross, Robert W.; Mire, Chad E.; Borisevich, Viktoriya; Geisbert, Joan B.; Fenton, Karla A.; Geisbert, Thomas W.

    2016-01-01

    Small-animal models have been developed for several Filoviridae species; however, serial adaptation was required to produce lethal infection. These adapted viruses have sequence changes in several genes, including those that modulate the host immune response. Nonhuman primate models do not require adaptation of filoviruses. Here, we describe lethal models of disease for Bundibugyo, Sudan, and Zaire species of Ebolavirus in the domestic ferret, using wild-type nonadapted viruses. Pathologic features were consistent with disease in primates. Of particular importance, this is the only known small-animal model developed for Bundibugyo and the only uniformly lethal animal model for Bundibugyo. PMID:27354371

  18. Recovery of the black-footed ferret: Progress and continuing challenges- Proceedings of the Symposium on the Status of the Black-footed Ferret and Its Habitat, Fort Collins, Colorado, January 28-29, 2004

    USGS Publications Warehouse

    Roelle, James E.; Miller, Brian J.; Godbey, Jerry L.; Biggins, Dean E.

    2006-01-01

    The black-footed ferret (Mustela nigripes) is a member of the weasel family (Mustelidae) and is closely related to the Siberian polecat (M. eversmannii) of Asian steppes and the European polecat (M. putorius). Compared to its relatives, the black-footed ferret is an extreme specialist, depending on the prairie dogs (Cynomys spp.) of North American grasslands for food and using prairie dog burrows for shelter. The black-footed ferret’s close association with prairie dogs was an important factor in its decline. Prairie dogs were regarded as an agricultural pest as human settlement progressed westward, and they became important hosts for plague as that disease colonized eastward from its sources of introduction on the west coast. Prairie dog numbers were dramatically reduced by poisoning, cropland conversions, and plague during the first half of the 20th century, and black-footed ferret populations declined precipitously. The black-footed ferret was included on the first lists of endangered species, and its status was precarious by the time the Endangered Species Act of 1973 was passed. Its rebound from a low point of 10 known individuals in spring of 1985 (Biggins and others, 2006) is impressive, but the species is not yet “recovered” in either the biological or legal sense (for further details, see Lockhart and others, this volume).

  19. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    SciTech Connect

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-11-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted.

  20. A proposal to conserve black-footed ferrets and the prairie dog ecosystem

    USGS Publications Warehouse

    Miller, Brian; Wemmer, Christen; Biggins, Dean; Reading, Richard P.

    1990-01-01

    Prairie dogs (Cynomys spp.) have been poisoned throughout this century because of grazing competition with livestock. Recent evidence showed these early claims were exaggerated, but animal control was already entrenched in government policy. As a result, ongoing government subsidized poisoning has reduced prairie dogs to about 2% of their former distribution. The reduction of prairie dogs diminished species diversity in the arid grasslands of North America, including the potential extinction of the black-footed ferret (Mustela nigripes). Cost-benefit analysis revealed that poisoning costs more than any grazing benefits accrued. This analysis did not consider the long-term costs of reversing ecosystem degradation, the intangible value of biological diversity as a public benefit, or the depletion of biotic resources as a loss of actual or potential wealth. The government presently finances the poisoning policy and the preservation of endangered species like the black-footed ferret, two apparently conflicting programs. We, therefore, propose an integrated management plan that considers both interests. We propose that federal monies allocated to the poisoning program be converted into a rebate for ranchers who manage livestock while preserving the prairie dog community. This would redirect funds and personnel already allocated to prairie dog eradication to an incentive for ranchers who manage for livestock and wildlife. Livestock interests and grassland biotic diversity would both benefit.

  1. Peripheral Leukocyte Migration in Ferrets in Response to Infection with Seasonal Influenza Virus

    PubMed Central

    Kim, Jin Hyang; York, Ian A.

    2016-01-01

    In order to better understand inflammation associated with influenza virus infection, we measured cell trafficking, via flow cytometry, to various tissues in the ferret model following infection with an A(H3N2) human seasonal influenza virus (A/Perth/16/2009). Changes in immune cells were observed in the blood, bronchoalveolar lavage fluid, and spleen, as well as lymph nodes associated with the site of infection or distant from the respiratory system. Nevertheless clinical symptoms were mild, with circulating leukocytes exhibiting rapid, dynamic, and profound changes in response to infection. Each of the biological compartments examined responded differently to influenza infection. Two days after infection, when infected ferrets showed peak fever, a marked, transient lymphopenia and granulocytosis were apparent in all infected animals. Both draining and distal lymph nodes demonstrated significant accumulation of T cells, B cells, and granulocytes at days 2 and 5 post-infection. CD8+ T cells significantly increased in spleen at days 2 and 5 post-infection; CD4+ T cells, B cells and granulocytes significantly increased at day 5. We interpret our findings as showing that lymphocytes exit the peripheral blood and differentially home to lymph nodes and tissues based on cell type and proximity to the site of infection. Monitoring leukocyte homing and trafficking will aid in providing a more detailed view of the inflammatory impact of influenza virus infection. PMID:27315117

  2. Dorso-Lateral Frontal Cortex of the Ferret Encodes Perceptual Difficulty during Visual Discrimination

    PubMed Central

    Zhou, Zhe Charles; Yu, Chunxiu; Sellers, Kristin K.; Fröhlich, Flavio

    2016-01-01

    Visual discrimination requires sensory processing followed by a perceptual decision. Despite a growing understanding of visual areas in this behavior, it is unclear what role top-down signals from prefrontal cortex play, in particular as a function of perceptual difficulty. To address this gap, we investigated how neurons in dorso-lateral frontal cortex (dl-FC) of freely-moving ferrets encode task variables in a two-alternative forced choice visual discrimination task with high- and low-contrast visual input. About two-thirds of all recorded neurons in dl-FC were modulated by at least one of the two task variables, task difficulty and target location. More neurons in dl-FC preferred the hard trials; no such preference bias was found for target location. In individual neurons, this preference for specific task types was limited to brief epochs. Finally, optogenetic stimulation confirmed the functional role of the activity in dl-FC before target touch; suppression of activity in pyramidal neurons with the ArchT silencing opsin resulted in a decrease in reaction time to touch the target but not to retrieve reward. In conclusion, dl-FC activity is differentially recruited for high perceptual difficulty in the freely-moving ferret and the resulting signal may provide top-down behavioral inhibition. PMID:27025995

  3. A proposal to conserve black-footed ferrets and the prairie dog ecosystem

    NASA Astrophysics Data System (ADS)

    Miller, Brian; Wemmer, Christen; Biggins, Dean; Reading, Richard

    1990-11-01

    Prairie dogs ( Cynomys spp.) have been poisoned throughout this century because of grazing competition with livestock. Recent evidence showed these early claims were exaggerated, but animal control was already entrenched in government policy. As a result, ongoing government subsidized poisoning has reduced prairie dogs to about 2% of their former distribution. The reduction of prairie dogs diminished species diversity in the arid grasslands of North America, including the potential extinction of the black-footed ferret ( Mustela nigripes). Cost-benefit analysis revealed that poisoning costs more than any grazing benefits accrued. This analysis did not consider the long-term costs of reversing ecosystem degradation, the intangible value of biological diversity as a public benefit, or the depletion of biotic resources as a loss of actual or potential wealth. The government presently finances the poisoning policy and the preservation of endangered species like the black-footed ferret, two apparently conflicting programs. We, therefore, propose an integrated management plan that considers both interests. We propose that federal monies allocated to the poisoning program be converted into a rebate for ranchers who manage livestock while preserving the prairie dog community. This would redirect funds and personnel already allocated to prairie dog eradication to an incentive for ranchers who manage for livestock and wildlife. Livestock interests and grassland biotic diversity would both benefit.

  4. Peripheral Leukocyte Migration in Ferrets in Response to Infection with Seasonal Influenza Virus.

    PubMed

    Music, Nedzad; Reber, Adrian J; Kim, Jin Hyang; York, Ian A

    2016-01-01

    In order to better understand inflammation associated with influenza virus infection, we measured cell trafficking, via flow cytometry, to various tissues in the ferret model following infection with an A(H3N2) human seasonal influenza virus (A/Perth/16/2009). Changes in immune cells were observed in the blood, bronchoalveolar lavage fluid, and spleen, as well as lymph nodes associated with the site of infection or distant from the respiratory system. Nevertheless clinical symptoms were mild, with circulating leukocytes exhibiting rapid, dynamic, and profound changes in response to infection. Each of the biological compartments examined responded differently to influenza infection. Two days after infection, when infected ferrets showed peak fever, a marked, transient lymphopenia and granulocytosis were apparent in all infected animals. Both draining and distal lymph nodes demonstrated significant accumulation of T cells, B cells, and granulocytes at days 2 and 5 post-infection. CD8+ T cells significantly increased in spleen at days 2 and 5 post-infection; CD4+ T cells, B cells and granulocytes significantly increased at day 5. We interpret our findings as showing that lymphocytes exit the peripheral blood and differentially home to lymph nodes and tissues based on cell type and proximity to the site of infection. Monitoring leukocyte homing and trafficking will aid in providing a more detailed view of the inflammatory impact of influenza virus infection. PMID:27315117

  5. Diabetic Ketoacidosis with Concurrent Pancreatitis, Pancreatic β Islet Cell Tumor, and Adrenal Disease in an Obese Ferret (Mustela putorius furo)

    PubMed Central

    Phair, Kristen A; Carpenter, James W; Schermerhorn, Thomas; Ganta, Chanran K; DeBey, Brad M

    2011-01-01

    A 5.5-y-old spayed female ferret (Mustela putorius furo) with a history of adrenal disease, respiratory disease, and chronic obesity was evaluated for progressive lethargy and ataxia, diminished appetite, and possible polyuria and polydipsia. Physical examination revealed obesity, lethargy, tachypnea, dyspnea, a pendulous abdomen, significant weakness and ataxia of the hindlimbs, prolonged skin tenting, and mild tail-tip alopecia. Clinicopathologic analysis revealed severe hyperglycemia, azotemia, an increased anion gap, glucosuria, ketonuria, proteinuria, and hematuria. Abdominal ultrasonography showed hyperechoic hepatomegaly, bilateral adrenomegaly, splenic nodules, mild peritoneal effusion, and thickened and mildly hypoechoic limbs of the pancreas with surrounding hyperechoic mesentery. Fine-needle aspirates of the liver were highly suggestive of hepatic lipidosis. In light of a diagnosis of concurrent diabetic ketoacidosis and pancreatitis, the ferret was treated with fluid therapy, regular and long-acting insulin administration, and pain medication. However, electrolyte derangements, metabolic acidosis, dyspnea, and the clinical appearance of the ferret progressively worsened despite treatment, and euthanasia was elected. Necropsy revealed severe hepatic lipidosis, severe suppurative pancreatitis and vacuolar degeneration of pancreatic islet cells, a pancreatic β islet cell tumor, bilateral adrenal cortical adenomas, and myocardial fibrosis. To our knowledge, this case represents the first report of concurrent diabetes mellitus, pancreatitis, pancreatic β islet cell tumor (insulinoma), and adrenal disease in a domestic ferret. The simultaneous existence of 3 endocrine diseases, pancreatitis, and their associated complications is a unique and clinically challenging situation. PMID:21838985

  6. The effects of compensated cardiac hypertrophy on dihydropyridine and ryanodine receptors in rat, ferret and guinea-pig hearts.

    PubMed

    Rannou, F; Sainte-Beuve, C; Oliviero, P; Do, E; Trouvé, P; Charlemagne, D

    1995-05-01

    The number of dihydropyridine and ryanodine receptors (DHP-R and RyR) has been measured in control and hypertrophied ventricles from rats, guinea pigs and ferrets to determine whether these two channels contribute to the alterations in excitation-contraction coupling (ECC), and in Ca2+ transient during compensated cardiac hypertrophy. We found that ventricular hypertrophy did not change the density of DHP-R. Mild hypertrophy did not alter the density of RyR in the rat but decreased it in the guinea-pig and in the ferret (30% and 36%, respectively). Severe hypertrophy decreased the density of RyR by 20% in the rat and by 34% in the guinea-pig. Therefore, the decrease is greater in ferret and guinea-pig hearts than in rat heart. We conclude that the sarcoplasmic reticulum (SR) Ca2+ release channels but not the L-type Ca2+ channels could contribute to the slowing of intracellular Ca2+ movements and to the reduced velocity of shortening of the hypertrophied hearts. We suggest that, in the guinea pig and ferret hearts which express only the beta myosin heavy chain (MHC) isoform, the reduced velocity of shortening during hypertrophy is related to the decrease in RyR density, whereas in the rat, it is regulated primarily via a shift in the MHC isoform, except in severe hypertrophy in which the moderate decrease in RyR would also be involved. PMID:7473781

  7. Combined alpha-tocopherol and ascorbic acid protects against smoke-induced lung squamous metaplasia in ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many epidemiological studies show the benefit of fruits and vegetables on reducing risk of lung cancer, the leading cause of cancer death in the United States. Previously, we demonstrated that cigarette smoke exposure (SM)-induced lung lesions in ferrets were prevented by a combination of carotene,...

  8. Sequential Infection in Ferrets with Antigenically Distinct Seasonal H1N1 Influenza Viruses Boosts Hemagglutinin Stalk-Specific Antibodies

    PubMed Central

    Kirchenbaum, Greg A.; Carter, Donald M.

    2015-01-01

    ABSTRACT Broadly reactive antibodies targeting the conserved hemagglutinin (HA) stalk region are elicited following sequential infection or vaccination with influenza viruses belonging to divergent subtypes and/or expressing antigenically distinct HA globular head domains. Here, we demonstrate, through the use of novel chimeric HA proteins and competitive binding assays, that sequential infection of ferrets with antigenically distinct seasonal H1N1 (sH1N1) influenza virus isolates induced an HA stalk-specific antibody response. Additionally, stalk-specific antibody titers were boosted following sequential infection with antigenically distinct sH1N1 isolates in spite of preexisting, cross-reactive, HA-specific antibody titers. Despite a decline in stalk-specific serum antibody titers, sequential sH1N1 influenza virus-infected ferrets were protected from challenge with a novel H1N1 influenza virus (A/California/07/2009), and these ferrets poorly transmitted the virus to naive contacts. Collectively, these findings indicate that HA stalk-specific antibodies are commonly elicited in ferrets following sequential infection with antigenically distinct sH1N1 influenza virus isolates lacking HA receptor-binding site cross-reactivity and can protect ferrets against a pathogenic novel H1N1 virus. IMPORTANCE The influenza virus hemagglutinin (HA) is a major target of the humoral immune response following infection and/or seasonal vaccination. While antibodies targeting the receptor-binding pocket of HA possess strong neutralization capacities, these antibodies are largely strain specific and do not confer protection against antigenic drift variant or novel HA subtype-expressing viruses. In contrast, antibodies targeting the conserved stalk region of HA exhibit broader reactivity among viruses within and among influenza virus subtypes. Here, we show that sequential infection of ferrets with antigenically distinct seasonal H1N1 influenza viruses boosts the antibody responses

  9. Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines.

    PubMed

    Welter, J; Taylor, J; Tartaglia, J; Paoletti, E; Stephensen, C B

    2000-07-01

    Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log(10) inverse mean titer +/- standard deviation of 2.30 +/- 0.12 and 2.20 +/- 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 +/- 0.57 versus 0.40 +/- 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 +/- 0. 54 and 1.28 +/- 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 +/- 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 +/- 0.32; n = 8, P = 7 x 10(-6)). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1

  10. Vaccination against Canine Distemper Virus Infection in Infant Ferrets with and without Maternal Antibody Protection, Using Recombinant Attenuated Poxvirus Vaccines

    PubMed Central

    Welter, Janet; Taylor, Jill; Tartaglia, James; Paoletti, Enzo; Stephensen, Charles B.

    2000-01-01

    Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log10 inverse mean titer ± standard deviation of 2.30 ± 0.12 and 2.20 ± 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 ± 0.57 versus 0.40 ± 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 ± 0.54 and 1.28 ± 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 ± 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 ± 0.32; n = 8, P = 7 × 10−6). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1.63 ± 0

  11. Transmission of H7N9 Influenza Viruses with a Polymorphism at PB2 Residue 627 in Chickens and Ferrets

    PubMed Central

    Luk, Geraldine S. M.; Leung, Connie Y. H.; Sia, Sin Fun; Choy, Ka-Tim; Zhou, Jie; Ho, Candy C. K.; Cheung, Peter P. H.; Lee, Elaine F.; Wai, Chris K. L.; Li, Pamela C. H.; Ip, Sin-Ming; Poon, Leo L. M.; Lindsley, William G.

    2015-01-01

    ABSTRACT Poultry exposure is a major risk factor for human H7N9 zoonotic infections, for which the mode of transmission remains unclear. We studied the transmission of genetically related poultry and human H7N9 influenza viruses differing by four amino acids, including the host determinant PB2 residue 627. A/Silkie chicken/HK/1772/2014 (SCk1772) and A/HK/3263/14 (HK3263) replicated to comparable titers in chickens, with superior oropharyngeal over cloacal shedding; both viruses transmitted efficiently among chickens via direct contact but inefficiently via the airborne route. Interspecies transmission via the airborne route was observed for ferrets exposed to the SCk1772- or HK3263-infected chickens, while low numbers of copies of influenza viral genome were detected in the air, predominantly at particle sizes larger than 4 μm. In ferrets, the human isolate HK3263 replicated to higher titers and transmitted more efficiently via direct contact than SCk1772. We monitored “intrahost” and “interhost” adaptive changes at PB2 residue 627 during infection and transmission of the Sck1772 that carried E627 and HK3263 that carried V/K/E polymorphism at 60%, 20%, and 20%, respectively. For SCk1772, positive selection for K627 over E627 was observed in ferrets during the chicken-to-ferret or ferret-to-ferret transmission. For HK3263 that contained V/K/E polymorphism, mixed V627 and E627 genotypes were transmitted among chickens while either V627 or K627 was transmitted to ferrets with a narrow transmission bottleneck. Overall, our results suggest direct contact as the main mode for H7N9 transmission and identify the PB2-V627 genotype with uncompromised fitness and transmissibility in both avian and mammalian species. IMPORTANCE We studied the modes of H7N9 transmission, as this information is crucial for developing effective control measures for prevention. Using chicken (SCk1772) and human (HK3263) H7N9 isolates that differed by four amino acids, including the host

  12. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    PubMed

    Mann, Alex J; Noulin, Nicolas; Catchpole, Andrew; Stittelaar, Koert J; de Waal, Leon; Veldhuis Kroeze, Edwin J B; Hinchcliffe, Michael; Smith, Alan; Montomoli, Emanuele; Piccirella, Simona; Osterhaus, Albert D M E; Knight, Alastair; Oxford, John S; Lapini, Giulia; Cox, Rebecca; Lambkin-Williams, Rob

    2014-01-01

    We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments) or intranasally (CSN adjuvanted and placebo treatments only) with clade 1 HPAI A/Vietnam/1194/2004 (H5N1) virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant mortality and

  13. A Recombinant Hendra virus G Glycoprotein-Based Subunit Vaccine Protects Ferrets from Lethal Hendra virus Challenge

    PubMed Central

    Pallister, Jackie; Middleton, Deborah; Wang, Lin-Fa; Klein, Reuben; Haining, Jessica; Robinson, Rachel; Yamada, Manabu; White, John; Payne, Jean; Feng, Yan-Ru; Chan, Yee-Peng; Broder, Christopher C.

    2011-01-01

    The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5,000 TCID50 of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible. PMID:21689706

  14. Low Dose Influenza Virus Challenge in the Ferret Leads to Increased Virus Shedding and Greater Sensitivity to Oseltamivir

    PubMed Central

    Whittaker, Catherine J.; Bruce, Christine; Ryan, Kathryn A.; Bean, Thomas J.; Rayner, Emma; Pearson, Geoff; Taylor, Irene; Dowall, Stuart; Plank, Jenna; Newman, Edmund; Barclay, Wendy S.; Dimmock, Nigel J.; Easton, Andrew J.; Hallis, Bassam; Silman, Nigel J.; Carroll, Miles W.

    2014-01-01

    Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09) induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu) of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu) and low (102 pfu) doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines. PMID:24709834

  15. A recombinant Hendra virus G glycoprotein-based subunit vaccine protects ferrets from lethal Hendra virus challenge.

    PubMed

    Pallister, Jackie; Middleton, Deborah; Wang, Lin-Fa; Klein, Reuben; Haining, Jessica; Robinson, Rachel; Yamada, Manabu; White, John; Payne, Jean; Feng, Yan-Ru; Chan, Yee-Peng; Broder, Christopher C

    2011-08-01

    The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirrors the disease seen in humans and horses with induction of systemic vasculitis, including involvement of the pulmonary and central nervous systems. This model of HeV infection in the ferret was used to assess the immunogenicity and protective efficacy of a subunit vaccine based on a recombinant soluble version of the HeV attachment glycoprotein G (HeVsG), adjuvanted with CpG. We report that ferrets vaccinated with a 100 μg, 20 μg or 4 μg dose of HeVsG remained free of clinical signs of HeV infection following a challenge with 5000 TCID₅₀ of HeV. In addition, and of considerable importance, no evidence of virus or viral genome was detected in any tissues or body fluids in any ferret in the 100 and 20 μg groups, while genome was detected in the nasal washes only of one animal in the 4 μg group. Together, our findings indicate that 100 μg or 20 μg doses of HeVsG vaccine can completely prevent a productive HeV infection in the ferret, suggesting that vaccination to prevent the infection and shedding of HeV is possible.

  16. Sequential Seasonal H1N1 Influenza Virus Infections Protect Ferrets against Novel 2009 H1N1 Influenza Virus

    PubMed Central

    Carter, Donald M.; Bloom, Chalise E.; Nascimento, Eduardo J. M.; Marques, Ernesto T. A.; Craigo, Jodi K.; Cherry, Joshua L.; Lipman, David J.

    2013-01-01

    Individuals <60 years of age had the lowest incidence of infection, with ∼25% of these people having preexisting, cross-reactive antibodies to novel 2009 H1N1 influenza. Many people >60 years old also had preexisting antibodies to novel H1N1. These observations are puzzling because the seasonal H1N1 viruses circulating during the last 60 years were not antigenically similar to novel H1N1. We therefore hypothesized that a sequence of exposures to antigenically different seasonal H1N1 viruses can elicit an antibody response that protects against novel 2009 H1N1. Ferrets were preinfected with seasonal H1N1 viruses and assessed for cross-reactive antibodies to novel H1N1. Serum from infected ferrets was assayed for cross-reactivity to both seasonal and novel 2009 H1N1 strains. These results were compared to those of ferrets that were sequentially infected with H1N1 viruses isolated prior to 1957 or more-recently isolated viruses. Following seroconversion, ferrets were challenged with novel H1N1 influenza virus and assessed for viral titers in the nasal wash, morbidity, and mortality. There was no hemagglutination inhibition (HAI) cross-reactivity in ferrets infected with any single seasonal H1N1 influenza viruses, with limited protection to challenge. However, sequential H1N1 influenza infections reduced the incidence of disease and elicited cross-reactive antibodies to novel H1N1 isolates. The amount and duration of virus shedding and the frequency of transmission following novel H1N1 challenge were reduced. Exposure to multiple seasonal H1N1 influenza viruses, and not to any single H1N1 influenza virus, elicits a breadth of antibodies that neutralize novel H1N1 even though the host was never exposed to the novel H1N1 influenza viruses. PMID:23115287

  17. Effect of dietary vitamin E and prey supplementation on semen quality in male black-footed ferrets (Mustela nigripes).

    PubMed

    Santymire, Rachel M; Lavin, Shana R; Branvold-Faber, Heather; Kreeger, Julie; Marinari, Paul

    2015-07-15

    Over the recent years, the captive population of the endangered black-footed ferret (Mustela nigripes; ferret) has experienced a decline in normal sperm (NS) morphology (from 50% to 16%), which may be linked to inbreeding depression or it may have been a dietary change. We examined the role of dietary vitamin E, selenium (SE), and vitamin A on serum levels of vitamin E, SE, and vitamin A and semen quality. Ferrets (n = 55 males) were randomly assigned to one of five diet treatments (n = 11 per treatment): (1) horsemeat diet (control); (2) horsemeat diet + vitamin E (400 IU/kg Dry Matter) daily; (3) horsemeat diet + whole prey; (4) horsemeat diet + vitamin E daily + whole prey; and (5) beef diet. Both blood (prediet and postdiet change) and diets were analyzed for vitamin E, vitamin A, and SE concentrations. Electroejaculates were collected monthly and evaluated for sperm concentration, sperm motility index (includes percent motile and forward progression), and percent NS. Results reveal that the beef and horsemeat diets had comparable (P = 0.05) vitamin E and SE concentrations and all diets met most nutrient requirements for small carnivores; however, the horsemeat diet was excessive in vitamin A and the beef diet was deficient in vitamin A. Vitamin E supplementation increased (χ1(2)=25.83; P < 0.001) serum vitamin E. Ferrets fed the beef diet or prey had improved (H4 = 15.596; P = 0.004) sperm motility index than the horsemeat control group, and ferrets fed the horsemeat diet supplemented with vitamin E had the lowest (H4 = 18.408; P = 0.001) NS. In conclusion, the high levels of vitamin A in the horsemeat diet could compete with vitamin E as evidence by serum levels, which may reduce reproductive success in this endangered species. PMID:25890779

  18. Behavioral responses of predator-naïve dwarf hamsters (Phodopus campbelli) to odor cues of the European ferret fed with different prey species.

    PubMed

    Apfelbach, Raimund; Soini, Helena A; Vasilieva, Nina Y; Novotny, Milos V

    2015-07-01

    Many mammalian predators are able to identify their prey by odors and, vice versa, numerous prey species recognize predator odors as well. The present paper reports on the behavioral responses of predator-naïve dwarf hamsters (Phodopus campbelli) towards the urine odors of carnivorous ferrets, which were raised on either a chicken, mouse or hamster diet. Chemical composition from ferret urines of the different diet groups was analyzed, while quantitative differences in urinary volatile constituents were observed through capillary gas chromatography–mass spectrometry. In a Y-maze arrangement, hamsters were offered several two-choice odor discrimination tasks and their behavior was quantified. Hamsters were easily able to discriminate the urine odor of ferrets fed with mice against ferrets fed with hamsters. This is probably the first report indicating that a prey species can distinguish urine odors of even an unknown predator species that has been fed different prey species. The analytical data complemented behavioral assays.

  19. A single dose of whole inactivated H7N9 influenza vaccine confers protection from severe disease but not infection in ferrets

    PubMed Central

    Wong, Sook-San; Jeevan, Trushar; Kercher, Lisa; Yoon, Sun-Woo; Petkova, Atanaska-Marinova; Crumpton, Jeri-Carol; Franks, John; Debeauchamp, Jennifer; Rubrum, Adam; Seiler, Patrick; Krauss, Scott; Webster, Robert; Webby, Richard J.

    2014-01-01

    The H7N9 influenza virus caused significant mortality and morbidity in infected humans during an outbreak in China in 2013 stimulating vaccine development efforts. As previous H7-based vaccines have been poorly immunogenic in humans we sought to determine the immunogenic and protective properties of an inactivated whole virus vaccine derived from a 2013 H7N9 virus in ferrets. As whole virus vaccine preparations have been shown to be more immunogenic in humans, but less likely to be used, than split or surface antigen formulations, we vaccinated ferrets with a single dose of 15, 30, or 50 μg of the vaccine and subsequently challenged with wild-type A/Anhui/1/2013 (H7N9) either by direct instillation or by contact with infected animals. Although ferrets vaccinated with higher doses of vaccine had higher serum hemagglutinin inhibition (HI) titers, the titers were still low. During subsequent instillation challenge, however, ferrets vaccinated with 50 μg of vaccine showed no illness and shed significantly less virus than mock vaccinated controls. All vaccinated ferrets had lower virus loads in their lungs as compared to controls. In a separate study where unvaccinated-infected ferrets were placed in the same cage with vaccinated-uninfected ferrets, vaccination did not prevent infection in the contact ferrets, although they showed a trend of lower viral load. Overall, we conclude that inactivated whole-virus H7N9 vaccine was able to reduce the severity of infection and viral load, despite the lack of hemagglutinin-inhibiting antibodies. PMID:24950355

  20. MRI-based morphometric characterizations of sexual dimorphism of the cerebrum of ferrets (Mustela putorius).

    PubMed

    Sawada, Kazuhiko; Horiuchi-Hirose, Miwa; Saito, Shigeyoshi; Aoki, Ichio

    2013-12-01

    The present study aimed to characterize cerebral morphology in young adult ferrets and its sexual dimorphism using high-field MRI and MRI-based morphometry. Ex vivo short TR/TE (typical T1-weighted parameter setting for conventional MRI) and T2W (long TR/TE) MRI with high spatial resolution at 7-tesla could visualize major subcortical and archicortical structures, i.e., the caudate nucleus, lentiform nucleus, amygdala and hippocampus. In particular, laminar organization of the olfactory bulb was identifiable by short TR/TE-MRI. The primary and secondary sulci observable in the adult ferret were distinguishable on either short TR/TE- or T2W-MRI, and the cortical surface morphology was reproduced well by 3D-rendered images obtained by short TR/TE-MRI. The cerebrum had a significantly lower volume in females than in males, which was attributed to region-specific volume reduction in the cerebral cortex and subcortical white matter in females. A sexual difference was also detected, manifested by an overall reduction in normalized signal ratios of short TR/TE-MRI in all cerebral structures examined in females than in males. On the other hand, an alternating array of higher and lower short TR/TE-MRI intensity transverse zones throughout the cortex, which was reminiscent of the functional cortical areas, was revealed by maximum intensity projection (MIP) in 3D. The normalized signal ratio of short TR/TE-MRI, but not T2W-MRI in the cortex, was negatively correlated with the density of myelin-basic protein immunoreactive fibers (males, r=-0.440; females, r=-0.481). The present results suggest that sexual differences in the adult ferret cerebrum are characterized by reduced volumes of the cerebral cortex and subcortical white matter in females, and by overall reductions in physiochemical characteristics, as obtained by short TR/TE-MRI, in females. It should be noted that short TR/TE-MRI-based MIP delineated functional cortical areas related to myeloarchitecture in 3D. Such an

  1. Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

    PubMed

    Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

    1997-02-01

    Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other Morbillivirus infections, including measles, this model will be useful in testing new candidate Morbillivirus vaccines. PMID:8995676

  2. Canine distemper virus (CDV) infection of ferrets as a model for testing Morbillivirus vaccine strategies: NYVAC- and ALVAC-based CDV recombinants protect against symptomatic infection.

    PubMed Central

    Stephensen, C B; Welter, J; Thaker, S R; Taylor, J; Tartaglia, J; Paoletti, E

    1997-01-01

    Canine distemper virus (CDV) infection of ferrets causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system (CNS). We have tested candidate CDV vaccines incorporating the fusion (F) and hemagglutinin (HA) proteins in the highly attenuated NYVAC strain of vaccinia virus and in the ALVAC strain of canarypox virus, which does not productively replicate in mammalian hosts. Juvenile ferrets were vaccinated twice with these constructs, or with an attenuated live-virus vaccine, while controls received saline or the NYVAC and ALVAC vectors expressing rabies virus glycoprotein. Control animals did not develop neutralizing antibody and succumbed to distemper after developing fever, weight loss, leukocytopenia, decreased activity, conjunctivitis, an erythematous rash typical of distemper, CNS signs, and viremia in peripheral blood mononuclear cells (as measured by reverse transcription-PCR). All three CDV vaccines elicited neutralizing titers of at least 1:96. All vaccinated ferrets survived, and none developed viremia. Both recombinant vaccines also protected against the development of symptomatic distemper. However, ferrets receiving the live-virus vaccine lost weight, became lymphocytopenic, and developed the erythematous rash typical of CDV. These data show that ferrets are an excellent model for evaluating the ability of CDV vaccines to protect against symptomatic infection. Because the pathogenesis and clinical course of CDV infection of ferrets is quite similar to that of other Morbillivirus infections, including measles, this model will be useful in testing new candidate Morbillivirus vaccines. PMID:8995676

  3. Neurotransmitter chemistry of lissencephalic cortex induced in ferrets by fetal treatment with methylazoxymethanol acetate.

    PubMed

    Johnston, M V; Haddad, R; Carman-Young, A; Coyle, J T

    1982-07-01

    Treatment of pregnant ferrets with 15 mg/kg of methylazoxymethanol acetate (MAM) at 33 days of fetal gestation results in offspring with cortical hypoplasia and lissencephally. Neurochemical analysis of 5 areas of cortex from 8-week-old offspring of MAM- or vehicle-treated jills indicated an overall enrichment in markers for catecholaminergic (tyrosine hydroxylase, norepinephrine) and cholinergic (choline acetyltransferase, acetylcholine) terminals but minimal change in the concentration of GABAergic markers (glutamate decarboxylase, gamma-aminobutyric acid); however, there did not appear to be a direct, inverse relationship between the concentration of catecholaminergic and cholinergic markers and the degree of hypoplasia in cortical subareas unlike what has been found previously in the rat. PMID:6125249

  4. Ultrastructural development of the medial superior olive (MSO) in the ferret.

    PubMed

    Brunso-Bechtold, J K; Henkel, C K; Linville, C

    1992-10-22

    When ferrets are born, four weeks before the onset of hearing, few synapses are evident in the medial superior olive (MSO). The synapses present are immature and almost exclusively found in the neuropil. The MSO somata are virtually devoid of synaptic contacts but are contacted by fine glial processes that increasingly ensheathe the somata during the first postnatal week. By P12, somatic synaptogenesis in the MSO is evident. Initially the terminals contain vesicles of irregular shape, size, and distribution. The glial lamellae appear to withdraw as the synaptic contacts form but continue to cover the asynaptic portions of the cell surface. The lamellae frequently extend from ensheathing the soma to encapsulate the immature terminals. During the next two weeks, synaptic density and terminal encapsulation proceed until the somata is surrounded by encapsulated synaptic terminals as in the adult ferret MSO. While most immature terminals contain round vesicles, during the first postnatal week some terminals with nonround vesicles can be distinguished. The first distinction between types of nonround vesicle-containing terminals, i.e., pleiomorphic and ovoid, is in the second postnatal week. This distinction becomes increasingly clear and by the end of the first postnatal month, terminal types can be reliably categorized. These observations indicate that: (1) synapses are present in the MSO neuropil one month prior to the onset of hearing, (2) the major period of synaptogenesis begins approximately two weeks prior to the onset of hearing, and (3) glial lamellae ensheathe MSO somata prior to the onset of somatic synaptogenesis, withdraw as synapses form, and subsequently re-extend to encapsulate newly formed synapses.

  5. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    SciTech Connect

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R.

    2014-03-15

    Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ∼1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.

  6. Sexual dimorphism of sulcal morphology of the ferret cerebrum revealed by MRI-based sulcal surface morphometry.

    PubMed

    Sawada, Kazuhiko; Horiuchi-Hirose, Miwa; Saito, Shigeyoshi; Aoki, Ichio

    2015-01-01

    The present study quantitatively assessed sexual dimorphism of cortical convolution and sulcal morphology in young adult ferrets by MRI-based sulcal surface morphometry. Ex vivo T1-weighted (short TR/TE) MRI of the ferret cerebrum was acquired with high spatial resolution at 7-tesla. The degree of cortical convolution, evaluated quantitatively based on 3D MRI data by sulcation index (SI), was significantly greater in males (0.553 ± 0.036) than in females (0.502 ± 0.043) (p < 0.001). The rostrocaudal distribution of the cortical convolution revealed a greater convolution in the frontal region of the cortex in males than in females and by a posterior extension of the convolution in the temporo-parieto-occipital region of males. Although the cerebral width in the frontal region was not different between sexes, the rhinal fissure and rostral region of splenial sulcus were more infolded in males than in females. On the contrary, the cerebral width was greater in males in the temporo-parieto-occipital region, and male-prominent posterior extension of infolding was noted in the lateral sulcus, caudal suprasylvian sulcus, pesudosylvian sulcus, hippocampal sulcus, and the caudal region of splenial sulcus. Notably, the caudal descending region of lateral sulcus was clearly infolded in males, but obscured in females. The present results suggest a region-related sexual dimorphism of the sulcal infolding, which is reflected by local cortical expansion in the ferret cerebrum. In particular, male-favored sulcal infolding with expansion of the temporo-parieto-occipital neocortex may be relevant to the human cerebral cortex regarding visuo-spatial and emotion processing, which are known to differ between sexes. The present results will provide fundamental information assessing sex-related changes in the regional sulcal infolding, when ferrets with experimentally-induced gyrification abnormality will be used as models for male-prevalent or male-earlier-onset neurodevelopmental

  7. Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

    PubMed Central

    Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.; Lin, Liyong; Kennedy, Ann R.

    2014-01-01

    Purpose/Objectives(s) The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events (SPEs), as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials Ferrets were exposed to 0 – 2 Gray (Gy) of whole body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results The lethal dose of radiation to 50% of the population, known as the LD50, of ferrets was established at ~ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 post-irradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early times post-irradiation when coagulopathies were present and progressively becoming more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions The data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is solely due to the cell killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation induced death at relatively low doses in large mammals. PMID:24495588

  8. Sexual dimorphism of sulcal morphology of the ferret cerebrum revealed by MRI-based sulcal surface morphometry

    PubMed Central

    Sawada, Kazuhiko; Horiuchi-Hirose, Miwa; Saito, Shigeyoshi; Aoki, Ichio

    2015-01-01

    The present study quantitatively assessed sexual dimorphism of cortical convolution and sulcal morphology in young adult ferrets by MRI-based sulcal surface morphometry. Ex vivo T1-weighted (short TR/TE) MRI of the ferret cerebrum was acquired with high spatial resolution at 7-tesla. The degree of cortical convolution, evaluated quantitatively based on 3D MRI data by sulcation index (SI), was significantly greater in males (0.553 ± 0.036) than in females (0.502 ± 0.043) (p < 0.001). The rostrocaudal distribution of the cortical convolution revealed a greater convolution in the frontal region of the cortex in males than in females and by a posterior extension of the convolution in the temporo-parieto-occipital region of males. Although the cerebral width in the frontal region was not different between sexes, the rhinal fissure and rostral region of splenial sulcus were more infolded in males than in females. On the contrary, the cerebral width was greater in males in the temporo-parieto-occipital region, and male-prominent posterior extension of infolding was noted in the lateral sulcus, caudal suprasylvian sulcus, pesudosylvian sulcus, hippocampal sulcus, and the caudal region of splenial sulcus. Notably, the caudal descending region of lateral sulcus was clearly infolded in males, but obscured in females. The present results suggest a region-related sexual dimorphism of the sulcal infolding, which is reflected by local cortical expansion in the ferret cerebrum. In particular, male-favored sulcal infolding with expansion of the temporo-parieto-occipital neocortex may be relevant to the human cerebral cortex regarding visuo-spatial and emotion processing, which are known to differ between sexes. The present results will provide fundamental information assessing sex-related changes in the regional sulcal infolding, when ferrets with experimentally-induced gyrification abnormality will be used as models for male-prevalent or male-earlier-onset neurodevelopmental

  9. The central localization of the vagus nerve in the ferret (Mustela putorius furo) and the mink (Mustela vison).

    PubMed

    Ranson, R N; Butler, P J; Taylor, E W

    1993-05-01

    The location of vagal preganglionic neurones (VPN) has been determined in nine ferrets (Mustela putorius furo) and seven mink (M. vison) using neuronal tract-tracing techniques employing horseradish peroxidase (HRP) and wheat-germ agglutinin conjugated HRP (WGA-HRP) mixtures injected into the nodose ganglion of the vagus nerve. Labelled VPN were located ipsilaterally in the dorsal motor nucleus of the vagus (DmnX), nucleus ambiguus (nA), and reticular formation (rf) of the medulla oblongata. In four of the ferrets, labelled VPN were also identified in the nucleus dorsomedialis (ndm) and the nucleus of the spinal accessory nerve (nspa). In a single mink a few labelled cells were observed in the ndm but no labelled VPN were found in the nspa. Labelling of afferent components of the vagus nerve was seen in two ferrets and two mink with the best labelling obtained following an injection of an HRP/WGA-HRP mixture into the nodose ganglion. Labelled afferents were observed to cross the ipsilateral spinal trigeminal tract (SpV) before entering the tractus solitarius (TS) in regions separate from the motor axons which exit the medulla in separate fasicles. Sensory terminal fields were identified bilaterally in the nucleus of the tractus solitarius (nTS) in both species and bilaterally in the area postrema (ap) of the ferret; however, the contralateral labelling was sparse in comparison to the densely labelled ipsilateral nTS/ap. Maximal terminal labelling was seen in regions just rostral and caudal to obex in both species.

  10. A Road Map for 21st Century Genetic Restoration: Gene Pool Enrichment of the Black-Footed Ferret

    PubMed Central

    Ryder, Oliver A.; Santymire, Rachel M.; Engelhardt, John F.; Novak, Ben J.

    2015-01-01

    Interspecies somatic cell nuclear transfer (iSCNT) could benefit recovery programs of critically endangered species but must be weighed with the risks of failure. To weigh the risks and benefits, a decision-making process that evaluates progress is needed. Experiments that evaluate the efficiency and efficacy of blastocyst, fetal, and post-parturition development are necessary to determine the success or failure or species-specific iSCNT programs. Here, we use the black-footed ferret (Mustela nigripes) as a case study for evaluating this emerging biomedical technology as a tool for genetic restoration. The black-footed ferret has depleted genetic variation yet genome resource banks contain genetic material of individuals not currently represented in the extant lineage. Thus, genetic restoration of the species is in theory possible and could help reduce the persistent erosion of genetic diversity from drift. Extensive genetic, genomic, and reproductive science tools have previously been developed in black-footed ferrets and would aid in the process of developing an iSCNT protocol for this species. Nonetheless, developing reproductive cloning will require years of experiments and a coordinated effort among recovery partners. The information gained from a well-planned research effort with the goal of genetic restoration via reproductive cloning could establish a 21st century model for evaluating and implementing conservation breeding that would be applicable to other genetically impoverished species. PMID:26304983

  11. S-phase duration is the main target of cell cycle regulation in neural progenitors of developing ferret neocortex.

    PubMed

    Turrero García, Miguel; Chang, YoonJeung; Arai, Yoko; Huttner, Wieland B

    2016-02-15

    The evolutionary expansion of the neocortex primarily reflects increases in abundance and proliferative capacity of cortical progenitors and in the length of the neurogenic period during development. Cell cycle parameters of neocortical progenitors are an important determinant of cortical development. The ferret (Mustela putorius furo), a gyrencephalic mammal, has gained increasing importance as a model for studying corticogenesis. Here, we have studied the abundance, proliferation, and cell cycle parameters of different neural progenitor types, defined by their differential expression of the transcription factors Pax6 and Tbr2, in the various germinal zones of developing ferret neocortex. We focused our analyses on postnatal day 1, a late stage of cortical neurogenesis when upper-layer neurons are produced. Based on cumulative 5-ethynyl-2'-deoxyuridine (EdU) labeling as well as Ki67 and proliferating cell nuclear antigen (PCNA) immunofluorescence, we determined the duration of the various cell cycle phases of the different neocortical progenitor subpopulations. Ferret neocortical progenitors were found to exhibit longer cell cycles than those of rodents and little variation in the duration of G1 among distinct progenitor types, also in contrast to rodents. Remarkably, the main difference in cell cycle parameters among the various progenitor types was the duration of S-phase, which became shorter as progenitors progressively changed transcription factor expression from patterns characteristic of self-renewal to those of neuron production. Hence, S-phase duration emerges as major target of cell cycle regulation in cortical progenitors of this gyrencephalic mammal.

  12. PATHOLOGY AND MOLECULAR DETECTION OF RABIES VIRUS IN FERRET BADGERS ASSOCIATED WITH A RABIES OUTBREAK IN TAIWAN.

    PubMed

    Chiou, Hue-Ying; Jeng, Chian-Ren; Wang, Hurng-Yi; Inoue, Satoshi; Chan, Fang-Tse; Liao, Jiunn-Wang; Chiou, Ming-Tang; Pang, Victor Fei

    2016-01-01

    Until Rabies virus (RABV) infection in Taiwan ferret badgers (TWFB; Melogale moschata subaurantiaca) was diagnosed in mid-June 2013, Taiwan had been considered rabies free for >50 yr. Although rabies has also been reported in ferret badgers in China, the pathologic changes and distribution of viral antigens of ferret badger-associated rabies have not been described. We performed a comprehensive pathologic study and molecular detection of rabies virus in three necropsied rabid TWFBs and evaluated archival paraffin-embedded tissue blocks of six other TWFBs necropsied during 2004 and 2012. As in other RABV-infected species, the characteristic pathologic changes in TWFBs were nonsuppurative meningoencephalomyelitis, ganglionitis, and the formation of typical intracytoplasmic Negri bodies, with the brain stem most affected. There was also variable spongiform degeneration, primarily in the perikaryon of neurons and neuropil, in the cerebral cortex, thalamus, and brain stem. In nonnervous system tissues, representative lesions included adrenal necrosis and lymphocytic interstitial sialadenitis. Immunohistochemical staining and fluorescent antibody test demonstrated viral antigens in the perikaryon of the neurons and axonal or dendritic processes throughout the nervous tissue and in the macrophages in various tissues. Similar to raccoons (Procyon lotor) and skunks (Mephitidae), the nervous tissue of rabid TWFBs displayed widely dispersed lesions, RABV antigens, and large numbers of Negri bodies. We traced the earliest rabid TWFB case back to 2004. PMID:26560756

  13. A Road Map for 21st Century Genetic Restoration: Gene Pool Enrichment of the Black-Footed Ferret.

    PubMed

    Wisely, Samantha M; Ryder, Oliver A; Santymire, Rachel M; Engelhardt, John F; Novak, Ben J

    2015-01-01

    Interspecies somatic cell nuclear transfer (iSCNT) could benefit recovery programs of critically endangered species but must be weighed with the risks of failure. To weigh the risks and benefits, a decision-making process that evaluates progress is needed. Experiments that evaluate the efficiency and efficacy of blastocyst, fetal, and post-parturition development are necessary to determine the success or failure or species-specific iSCNT programs. Here, we use the black-footed ferret (Mustela nigripes) as a case study for evaluating this emerging biomedical technology as a tool for genetic restoration. The black-footed ferret has depleted genetic variation yet genome resource banks contain genetic material of individuals not currently represented in the extant lineage. Thus, genetic restoration of the species is in theory possible and could help reduce the persistent erosion of genetic diversity from drift. Extensive genetic, genomic, and reproductive science tools have previously been developed in black-footed ferrets and would aid in the process of developing an iSCNT protocol for this species. Nonetheless, developing reproductive cloning will require years of experiments and a coordinated effort among recovery partners. The information gained from a well-planned research effort with the goal of genetic restoration via reproductive cloning could establish a 21st century model for evaluating and implementing conservation breeding that would be applicable to other genetically impoverished species.

  14. Environmental Conditions Affect Exhalation of H3N2 Seasonal and Variant Influenza Viruses and Respiratory Droplet Transmission in Ferrets

    PubMed Central

    Gustin, Kortney M.; Belser, Jessica A.; Veguilla, Vic; Zeng, Hui; Katz, Jacqueline M.; Tumpey, Terrence M.; Maines, Taronna R.

    2015-01-01

    The seasonality of influenza virus infections in temperate climates and the role of environmental conditions like temperature and humidity in the transmission of influenza virus through the air are not well understood. Using ferrets housed at four different environmental conditions, we evaluated the respiratory droplet transmission of two influenza viruses (a seasonal H3N2 virus and an H3N2 variant virus, the etiologic virus of a swine to human summertime infection) and concurrently characterized the aerosol shedding profiles of infected animals. Comparisons were made among the different temperature and humidity conditions and between the two viruses to determine if the H3N2 variant virus exhibited enhanced capabilities that may have contributed to the infections occurring in the summer. We report here that although increased levels of H3N2 variant virus were found in ferret nasal wash and exhaled aerosol samples compared to the seasonal H3N2 virus, enhanced respiratory droplet transmission was not observed under any of the environmental settings. However, overall environmental conditions were shown to modulate the frequency of influenza virus transmission through the air. Transmission occurred most frequently at 23°C/30%RH, while the levels of infectious virus in aerosols exhaled by infected ferrets agree with these results. Improving our understanding of how environmental conditions affect influenza virus infectivity and transmission may reveal ways to better protect the public against influenza virus infections. PMID:25969995

  15. A Road Map for 21st Century Genetic Restoration: Gene Pool Enrichment of the Black-Footed Ferret.

    PubMed

    Wisely, Samantha M; Ryder, Oliver A; Santymire, Rachel M; Engelhardt, John F; Novak, Ben J

    2015-01-01

    Interspecies somatic cell nuclear transfer (iSCNT) could benefit recovery programs of critically endangered species but must be weighed with the risks of failure. To weigh the risks and benefits, a decision-making process that evaluates progress is needed. Experiments that evaluate the efficiency and efficacy of blastocyst, fetal, and post-parturition development are necessary to determine the success or failure or species-specific iSCNT programs. Here, we use the black-footed ferret (Mustela nigripes) as a case study for evaluating this emerging biomedical technology as a tool for genetic restoration. The black-footed ferret has depleted genetic variation yet genome resource banks contain genetic material of individuals not currently represented in the extant lineage. Thus, genetic restoration of the species is in theory possible and could help reduce the persistent erosion of genetic diversity from drift. Extensive genetic, genomic, and reproductive science tools have previously been developed in black-footed ferrets and would aid in the process of developing an iSCNT protocol for this species. Nonetheless, developing reproductive cloning will require years of experiments and a coordinated effort among recovery partners. The information gained from a well-planned research effort with the goal of genetic restoration via reproductive cloning could establish a 21st century model for evaluating and implementing conservation breeding that would be applicable to other genetically impoverished species. PMID:26304983

  16. PATHOLOGY AND MOLECULAR DETECTION OF RABIES VIRUS IN FERRET BADGERS ASSOCIATED WITH A RABIES OUTBREAK IN TAIWAN.

    PubMed

    Chiou, Hue-Ying; Jeng, Chian-Ren; Wang, Hurng-Yi; Inoue, Satoshi; Chan, Fang-Tse; Liao, Jiunn-Wang; Chiou, Ming-Tang; Pang, Victor Fei

    2016-01-01

    Until Rabies virus (RABV) infection in Taiwan ferret badgers (TWFB; Melogale moschata subaurantiaca) was diagnosed in mid-June 2013, Taiwan had been considered rabies free for >50 yr. Although rabies has also been reported in ferret badgers in China, the pathologic changes and distribution of viral antigens of ferret badger-associated rabies have not been described. We performed a comprehensive pathologic study and molecular detection of rabies virus in three necropsied rabid TWFBs and evaluated archival paraffin-embedded tissue blocks of six other TWFBs necropsied during 2004 and 2012. As in other RABV-infected species, the characteristic pathologic changes in TWFBs were nonsuppurative meningoencephalomyelitis, ganglionitis, and the formation of typical intracytoplasmic Negri bodies, with the brain stem most affected. There was also variable spongiform degeneration, primarily in the perikaryon of neurons and neuropil, in the cerebral cortex, thalamus, and brain stem. In nonnervous system tissues, representative lesions included adrenal necrosis and lymphocytic interstitial sialadenitis. Immunohistochemical staining and fluorescent antibody test demonstrated viral antigens in the perikaryon of the neurons and axonal or dendritic processes throughout the nervous tissue and in the macrophages in various tissues. Similar to raccoons (Procyon lotor) and skunks (Mephitidae), the nervous tissue of rabid TWFBs displayed widely dispersed lesions, RABV antigens, and large numbers of Negri bodies. We traced the earliest rabid TWFB case back to 2004.

  17. Disruption of neuroendocrine stress responses to acute ferret odor by medial, but not central amygdala lesions in rats

    PubMed Central

    Masini, Cher V.; Sasse, Sarah K.; Garcia, Robert J.; Nyhuis, Tara J.; Day, Heidi E.W.; Campeau, Serge

    2009-01-01

    Investigations of the neural pathways associated with responses to predators have implicated the medial amygdala (MeA) as an important region involved in defensive behaviors. To our knowledge, however, the involvement of the MeA in neuroendocrine responses to predator odor exposure has not been investigated. Therefore, the present study examined the effects of MeA disruption in rats exposed to ferret or control odor on hypothalamo-pituitary-adrenocortical (HPA) axis activation. Bilateral lesions of the MeA were made in Sprague- Dawley rats with the neurotoxin ibotenic acid (10 µg/µl; 0.3 µl /side). As a control for regional specificity, additional groups of rats were given lesions in the central amygdala (CeA). One week after recovery, the rats were exposed to ferret or strawberry control towels in small cages to examine HPA axis responses as determined by plasma corticosterone and adrenocorticotropin hormone (ACTH) levels. Rats with complete bilateral MeA but not CeA lesions displayed significantly less corticosterone and ACTH release compared to sham-operated control rats only in the ferret odor conditions. These results suggest that the MeA is an important structure involved in the HPA axis responses to predator odors, in support of previous studies investigating behavioral responses under similar conditions. PMID:19615352

  18. Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

    PubMed Central

    Stittelaar, Koert J.; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J.B.; Fraaij, Pieter L.A.; van Baalen, Carel A.; van Kampen, Jeroen J.A.; van der Vries, Erhard; Osterhaus, Albert D.M.E.; de Swart, Rik L.

    2016-01-01

    Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies. PMID:27314379

  19. Differential Pathological and Immune Responses in Newly Weaned Ferrets Are Associated with a Mild Clinical Outcome of Pandemic 2009 H1N1 Infection

    PubMed Central

    Huang, Stephen S. H.; Banner, David; Degousee, Norbert; Leon, Alberto J.; Xu, Louling; Paquette, Stephane G.; Kanagasabai, Thirumagal; Fang, Yuan; Rubino, Salvatore; Rubin, Barry; Kelvin, Alyson A.

    2012-01-01

    Young children are typically considered a high-risk group for disease associated with influenza virus infection. Interestingly, recent clinical reports suggested that young children were the smallest group of cases with severe pandemic 2009 H1N1 (H1N1pdm) influenza virus infection. Here we established a newly weaned ferret model for the investigation of H1N1pdm infection in young age groups compared to adults. We found that young ferrets had a significantly milder fever and less weight loss than adult ferrets, which paralleled the mild clinical symptoms in the younger humans. Although there was no significant difference in viral clearance, disease severity was associated with pulmonary pathology, where newly weaned ferrets had an earlier pathology improvement. We examined the immune responses associated with protection of the young age group during H1N1pdm infection. We found that interferon and regulatory interleukin-10 responses were more robust in the lungs of young ferrets. In contrast, myeloperoxidase and major histocompatibility complex responses were persistently higher in the adult lungs; as well, the numbers of inflammation-prone granulocytes were highly elevated in the adult peripheral blood. Importantly, we observed that H1N1pdm infection triggered formation of lung structures that resembled inducible bronchus-associated lymphoid tissues (iBALTs) in young ferrets which were associated with high levels of homeostatic chemokines CCL19 and CXCL13, but these were not seen in the adult ferrets with severe disease. These results may be extrapolated to a model of the mild disease seen in human children. Furthermore, these mechanistic analyses provide significant new insight into the developing immune system and effective strategies for intervention and vaccination against respiratory viruses. PMID:23055557

  20. Use of a GnRH vaccine, GonaCon, for prevention and treatment of adrenocortical disease (ACD) in domestic ferrets.

    PubMed

    Miller, Lowell A; Fagerstone, Kathleen A; Wagner, Robert A; Finkler, Mark

    2013-09-23

    Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets. PMID

  1. Airborne Transmission of Highly Pathogenic H7N1 Influenza Virus in Ferrets

    PubMed Central

    Finch, Courtney; Shao, Hongxia; Angel, Matthew; Chen, Hongjun; Capua, Ilaria; Cattoli, Giovanni; Monne, Isabella

    2014-01-01

    ABSTRACT Avian H7 influenza viruses are recognized as potential pandemic viruses, as personnel often become infected during poultry outbreaks. H7 infections in humans typically cause mild conjunctivitis; however, the H7N9 outbreak in the spring of 2013 has resulted in severe respiratory disease. To date, no H7 viruses have acquired the ability for sustained transmission among humans. Airborne transmission is considered a requirement for the emergence of pandemic influenza, and advanced knowledge of the molecular changes or signature required for transmission would allow early identification of pandemic vaccine seed stocks, screening and stockpiling of antiviral compounds, and eradication efforts focused on flocks harboring threatening viruses. Thus, we sought to determine if a highly pathogenic influenza A H7N1 (A/H7N1) virus with no history of human infection could become capable of airborne transmission among ferrets. We show that after 10 serial passages, A/H7N1 developed the ability to be transmitted to cohoused and airborne contact ferrets. Four amino acid mutations (PB2 T81I, NP V284M, and M1 R95K and Q211K) in the internal genes and a minimal amino acid mutation (K/R313R) in the stalk region of the hemagglutinin protein were associated with airborne transmission. Furthermore, transmission was not associated with loss of virulence. These findings highlight the importance of the internal genes in host adaptation and suggest that natural isolates carrying these mutations be further evaluated. Our results demonstrate that a highly pathogenic avian H7 virus can become capable of airborne transmission in a mammalian host, and they support ongoing surveillance and pandemic H7 vaccine development. IMPORTANCE The major findings of this report are that a highly pathogenic strain of H7N1 avian influenza virus can be adapted to become capable of airborne transmission in mammals without mutations altering receptor specificity. Changes in receptor specificity have been

  2. Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1)

    PubMed Central

    2010-01-01

    Background There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1) virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1) through intranasal verses inhalation routes was analyzed. Results Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1). The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 101, 102, 103, or 104 infectious virus particles per ferret. Conclusions Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1) is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation. PMID:20843329

  3. Vaccination with F1-V fusion protein protects black-footed ferrets (Mustela nigripes) against plague upon oral challenge with Yersinia pestis

    USGS Publications Warehouse

    Rocke, T.E.; Smith, S.; Marinari, P.; Kreeger, J.; Enama, J.T.; Powell, B.S.

    2008-01-01

    Previous studies have established that vaccination of black-footed ferrets (Mustela nigripes) with F1-V fusion protein by subcutaneous (SC) injection protects the animals against plague upon injection of the bacterium Yersinia pestis. This study demonstrates that the F1-V antigen can also protect ferrets against plague contracted via ingestion of a Y. pestis-infected mouse, a probable route for natural infection. Eight black-footed ferret kits were vaccinated with F1-V protein by SC injection at approximately 60 days-of-age. A booster vaccination was administered 3 mo later via SC injection. Four additional ferret kits received placebos. The animals were challenged 6 wk after the boost by feeding each one a Y. pestis-infected mouse. All eight vaccinates survived challenge, while the four controls succumbed to plague within 3 days after exposure. To determine the duration of antibody postvaccination, 18 additional black-footed ferret kits were vaccinated and boosted with F1-V by SC injection at 60 and 120 days-of-age. High titers to both F1 and V (mean reciprocal titers of 18,552 and 99,862, respectively) were found in all vaccinates up to 2 yr postvaccination, whereas seven control animals remained antibody negative throughout the same time period. ?? Wildlife Disease Association 2008.

  4. Safety, immunogencity, and efficacy of a cold-adapted A/Ann Arbor/6/60 (H2N2) vaccine in mice and ferrets

    SciTech Connect

    Chen, Grace L.; Lamirande, Elaine W.; Jin Hong; Kemble, George; Subbarao, Kanta

    2010-03-01

    We studied the attenuation, immunogenicity and efficacy of the cold-adapted A/Ann Arbor/6/60 (AA ca) (H2N2) virus in mice and ferrets to evaluate its use in the event of an H2 influenza pandemic. The AA ca virus was restricted in replication in the respiratory tract of mice and ferrets. In mice, 2 doses of vaccine elicited a > 4-fold rise in hemagglutination-inhibition (HAI) titer and resulted in complete inhibition of viral replication following lethal homologous wild-type virus challenge. In ferrets, a single dose of the vaccine elicited a > 4-fold rise in HAI titer and conferred complete protection against homologous wild-type virus challenge in the upper respiratory tract. In both mice and ferrets, the AA ca virus provided significant protection from challenge with heterologous H2 virus challenge in the respiratory tract. The AA ca vaccine is safe, immunogenic, and efficacious against homologous and heterologous challenge in mice and ferrets, supporting the evaluation of this vaccine in clinical trials.

  5. Lack of transmission of a human influenza virus with avian receptor specificity between ferrets is not due to decreased virus shedding but rather a lower infectivity in vivo.

    PubMed

    Roberts, Kim L; Shelton, Holly; Scull, Margaret; Pickles, Raymond; Barclay, Wendy S

    2011-08-01

    Influenza virus attaches to host cells by sialic acid (SA). Human influenza viruses show preferential affinity for α2,6-linked SA, whereas avian influenza viruses bind α2,3-linked SA. In this study, mutation of the haemagglutinin receptor-binding site of a human H3N2 influenza A virus to switch binding to α2,3-linked SA did not eliminate infection of ferrets but prevented transmission, even in a co-housed model. The mutant virus was shed from the noses of ferrets directly inoculated with virus in the same amounts and for the same length of time as wild-type virus. Mutant virus infection was localized to the same anatomical regions of the upper respiratory tract of directly inoculated animals. Interestingly, wild-type virus was more readily neutralized than the mutant virus in vitro by ferret nasal washes containing mucus. Moreover after inoculation of equal doses, the mutant virus grew poorly in ex vivo ferret nasal turbinate tissue compared with wild-type virus. The dose of mutant virus required to establish infection in the directly inoculated ferrets was 40-fold higher than for wild-type virus. It was concluded that minimum infectious dose is a predictor of virus transmissibility and it is suggested that, as virus passes from one host to another through stringent environmental conditions, viruses with a preference for α2,3-linked SA are unlikely to inoculate a new mammalian host in sufficient quantities to initiate a productive infection.

  6. Transneuronal tracing of neural pathways controlling an abdominal muscle, rectus abdominis, in the ferret.

    PubMed

    Billig, I; Foris, J M; Card, J P; Yates, B J

    1999-02-27

    Abdominal muscles participate in generating a large number of behaviors and reflex responses, including expiration, coughing, sneezing, vomiting, postural control, production of speech, straining, facilitation of venous return to the heart, and reaction to vestibular stimulation. However, the only premotor neurons that have been conclusively shown to influence abdominal motoneurons are located in nucleus retroambiguus, the expiratory region of the caudal ventral respiratory group. In the present study, the neural circuitry controlling the activity of one abdominal muscle, rectus abdominis, was mapped using the transneuronal tracer pseudorabies virus (PRV) in the ferret. Injections of PRV into rectus abdominis labeled large presumed motoneurons in the ventral horn of T12-L4, and smaller presumed interneurons that were scattered in laminae VII, VIII, IX, and X of T4-L4. In addition, neurons in several areas of the medulla and caudal pons, including the retroambigual nucleus, medial and ventromedial reticular formation, nucleus prepositus hypoglossi, vestibular nuclei, and raphe nuclei, were infected by transynaptic passage of PRV from rectus abdominis motoneurons. Thus, the multifunctional roles of abdominal muscles appear to be coordinated by premotor neurons located in both the spinal cord and several regions of the brainstem. PMID:10023028

  7. Modeling host responses in ferrets during A/California/07/2009 influenza infection

    PubMed Central

    Rowe, Thomas; León, Alberto J.; Crevar, Corey J.; Carter, Donald M.; Xu, Luoling; Ran, Longsi; Fang, Yuan; Cameron, Cheryl M.; Cameron, Mark J.; Banner, David; Ng, Derek CK; Ran, Ran; Weirback, Heather K.; Wiley, Clayton A.; Kelvin, David J.; Ross, Ted M.

    2010-01-01

    Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009. Interestingly, the drop in innate immune gene expression was replaced by a significant increase of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-influenza antibodies were first observed on day 7, commensurate with the viral clearance. We propose that lung pathology in humans occurs during the innate phase of host immunity and a delay or failure to switch to the adaptive phase may contribute to morbidity and mortality during severe 2009-H1N1 infections. PMID:20334888

  8. Eyedrop Vaccination Induced Systemic and Mucosal Immunity against Influenza Virus in Ferrets.

    PubMed

    Yoon, Sangchul; Kim, Eun-Do; Song, Min-Suk; Han, Soo Jung; Park, Tae Kwann; Choi, Kyoung Sub; Choi, Young-Ki; Seo, Kyoung Yul

    2016-01-01

    We investigated eyedrop vaccination (EDV) in pre-clinical development for immunological protection against influenza and for potential side effects involving ocular inflammation and the central nervous system (CNS). Live attenuated influenza EDV, CA07 (H1N1), PZ-4 (H1N2) and Uruguay (H3N2), induced both systemic and mucosal virus-specific antibody responses in ferrets. In addition, EDV resulted in a clinically significant protection against viral challenge, and suppression of viral replication in nasal secretion and lung tissue. Regarding safety, we found that administered EDV flow through the tear duct to reach the base of nasal cavity, and thus do not contact the olfactory bulb. All analyses for potential adverse effects due to EDV, including histological and functional examinations, did not reveal significant side effects. On the basis of these findings, we propose that EDV as effective, while being a safe administration route with minimum local side effects, CNS invasion, or visual function disturbance. PMID:27333331

  9. Development of contralateral and ipsilateral frequency representations in ferret primary auditory cortex.

    PubMed

    Mrsic-Flogel, Thomas D; Versnel, Huib; King, Andrew J

    2006-02-01

    Little is known about the maturation of functional maps in the primary auditory cortex (A1) after the onset of sensory experience. We used intrinsic signal imaging to examine the development of the tonotopic organization of ferret A1 with respect to contralateral and ipsilateral tone stimulation. Sound-evoked responses were recorded as early as postnatal day (P) 33, a few days after hearing onset. From P36 onwards, pure tone stimuli evoked restricted, tonotopically organized patches of activity. There was an age-dependent increase in the cortical area representing each octave, with a disproportionate expansion of cortical territory representing frequencies > 4 kHz after P60. Similar tonotopic maps were observed following stimulation of the contralateral and ipsilateral ears. During the first few weeks following hearing onset, no differences were found in the area of cortical activation or in the magnitude of the optical responses evoked by stimulation of each ear. In older animals, however, contralateral stimuli evoked stronger responses and activated a larger A1 area than ipsilateral stimuli. Our findings indicate that neither the tonotopic organization nor the representation of inputs from each ear reach maturity until approximately 1 month after hearing onset. These results have important implications for cortical signal processing in juvenile animals. PMID:16487158

  10. Single-unit Analysis of Somatosensory Processing in Core Auditory Cortex of Hearing Ferrets

    PubMed Central

    Meredith, M. Alex; Allman, Brian L.

    2014-01-01

    The recent findings in several species that primary auditory cortex processes non-auditory information have largely overlooked the possibility for somatosensory effects. Therefore, the present investigation examined the core auditory cortices (anterior – AAF, and primary auditory-- A1, fields) for tactile responsivity. Multiple single-unit recordings from anesthetized ferret cortex yielded histologically verified neurons (n=311) tested with electronically controlled auditory, visual and tactile stimuli and their combinations. Of the auditory neurons tested, a small proportion (17%) was influenced by visual cues, but a somewhat larger number (23%) was affected by tactile stimulation. Tactile effects rarely occurred alone and spiking responses were observed in bimodal auditory-tactile neurons. However, the broadest tactile effect that was observed, which occurred in all neuron types, was that of suppression of the response to a concurrent auditory cue. The presence of tactile effects in core auditory cortices was supported by a substantial anatomical projection from the rostral suprasylvian sulcal somatosensory area. Collectively, these results demonstrate that crossmodal effects in auditory cortex are not exclusively visual and that somatosensation plays a significant role in modulation of acoustic processing and indicate that crossmodal plasticity following deafness may unmask these existing non-auditory functions. PMID:25728185

  11. NS1-mediated delay of type I interferon induction contributes to influenza A virulence in ferrets.

    PubMed

    Meunier, Isabelle; von Messling, Veronika

    2011-07-01

    Interference of the influenza A virus non-structural protein NS1 with type I interferon (IFN) signalling has been characterized extensively in vitro. To assess the contribution of NS1 to the virulence of a specific strain, we generated recombinant USSR/90/77 viruses bearing the NS1 proteins of the attenuated strain PR/8/34 or the highly pathogenic strain 1918 'Spanish flu', all belonging to the H1N1 subtype. In vitro, the extent of interference with type I IFN production exerted by the different NS1 proteins correlated with the reported virulence of the respective strain. Infection of ferrets with the recombinant viruses revealed that the presence of the 1918 NS1 resulted in a slightly more severe disease with generally higher clinical scores and increased lung pathology. Analysis of mRNA from nasal wash cells revealed that viruses carrying the 1918 and, to a lesser extent, USSR/90/77 NS1 proteins caused a delay in upregulation of type I IFNs compared with the NS1 PR/8/34-expressing virus, demonstrating the importance of NS1 for early host-response control and virulence.

  12. Adaptive, behaviorally-gated, persistent encoding of task-relevant auditory information in ferret frontal cortex

    PubMed Central

    Fritz, Jonathan B.; David, Stephen V.; Radtke-Schuller, Susanne; Yin, Pingbo; Shamma, Shihab A.

    2010-01-01

    Top-down signals from frontal cortex (FC) are conjectured to play a critical role in cognitive control of sensory processing. To explore this interaction, we compared activity in ferret FC and primary auditory cortex (A1) during auditory and visual tasks requiring discrimination between classes of reference and target stimuli. FC responses were behaviorally-gated, selectively encoded the timing and invariant behavioral meaning of target stimuli, could be rapid in onset, and sometimes persisted for hours following behavior. This mirrors earlier findings in A1that attention triggered rapid, selective, persistent, task-related changes in spectrotemporal receptive fields. Simultaneously recorded local field potentials (LFPs) revealed behaviorally-gated changes in inter-areal coherence, selectively modulated between FC and focal regions of A1 responsive to target sounds. These results suggest that A1 and FC dynamically establish a functional connection during auditory behavior that shapes the flow of sensory information and maintains a persistent trace of recent task-relevant stimulus features. PMID:20622871

  13. Angiotensin II stimulates sodium-dependent proton extrusion in perfused ferret heart.

    PubMed

    Grace, A A; Metcalfe, J C; Weissberg, P L; Bethell, H W; Vandenberg, J I

    1996-06-01

    The Na+/H+ antiport and Na(+)-HCO3- coinflux carrier contribute to recovery from intracellular acidosis in cardiac tissue. The effects of angiotensin II (10(-12)-10(-6) M) on H+ fluxes after intracellular acid loading and during reperfusion after myocardial ischemia have been investigated in the isovolumic, Langendorff-perfused ferret heart. Intracellular pH (pHi) was estimated using 31P nuclear magnetic resonance (NMR) spectroscopy from the chemical shift of intracellular deoxyglucose-6-phosphate or inorganic phosphate. Angiotensin II produced concentration-dependent stimulation (maximum at 10(-6) M: 67%) of 5-(N-ethyl-N-isopropyl)amiloride (EIPA)-sensitive Na(+)-dependent of H+ efflux consistent with stimulation of the Na+/H+ antiport. Half-maximal stimulation of H+ efflux occurred at approximately 10(-9) M, which is close to the dissociation constant of the cardiac angiotensin AT1 receptor. Stimulation via this receptor was confirmed with the nonpeptide AT1 receptor blocker, GR-117289. Angiotensin II had less pronounced effects on HCO3(-)-dependent pHi recovery after acid loading with no effect on pHi recovery after intracellular alkalosis. During reperfusion, angiotensin II significantly increased H+ extrusion but impaired contractile recovery. The results support the hypothesis that angiotensin II facilitates H+ extrusion in the heart. This may help maintain physiological homeostasis, but the hypothesized obligated Na+ influx could exacerbate cellular dysfunction during reperfusion. PMID:8764151

  14. Eyedrop Vaccination Induced Systemic and Mucosal Immunity against Influenza Virus in Ferrets

    PubMed Central

    Song, Min-Suk; Han, Soo Jung; Park, Tae Kwann; Choi, Kyoung Sub; Choi, Young-Ki; Seo, Kyoung Yul

    2016-01-01

    We investigated eyedrop vaccination (EDV) in pre-clinical development for immunological protection against influenza and for potential side effects involving ocular inflammation and the central nervous system (CNS). Live attenuated influenza EDV, CA07 (H1N1), PZ-4 (H1N2) and Uruguay (H3N2), induced both systemic and mucosal virus-specific antibody responses in ferrets. In addition, EDV resulted in a clinically significant protection against viral challenge, and suppression of viral replication in nasal secretion and lung tissue. Regarding safety, we found that administered EDV flow through the tear duct to reach the base of nasal cavity, and thus do not contact the olfactory bulb. All analyses for potential adverse effects due to EDV, including histological and functional examinations, did not reveal significant side effects. On the basis of these findings, we propose that EDV as effective, while being a safe administration route with minimum local side effects, CNS invasion, or visual function disturbance. PMID:27333331

  15. Oseltamivir–Resistant Pandemic H1N1/2009 Influenza Virus Possesses Lower Transmissibility and Fitness in Ferrets

    PubMed Central

    Duan, Susu; Boltz, David A.; Seiler, Patrick; Li, Jiang; Bragstad, Karoline; Nielsen, Lars P.; Webby, Richard J.; Webster, Robert G.; Govorkova, Elena A.

    2010-01-01

    The neuraminidase (NA) inhibitor oseltamivir offers an important immediate option for the control of influenza, and its clinical use has increased substantially during the recent H1N1 pandemic. In view of the high prevalence of oseltamivir-resistant seasonal H1N1 influenza viruses in 2007–2008, there is an urgent need to characterize the transmissibility and fitness of oseltamivir-resistant H1N1/2009 viruses, although resistant variants have been isolated at a low rate. Here we studied the transmissibility of a closely matched pair of pandemic H1N1/2009 clinical isolates, one oseltamivir-sensitive and one resistant, in the ferret model. The resistant H275Y mutant was derived from a patient on oseltamivir prophylaxis and was the first oseltamivir-resistant isolate of the pandemic virus. Full genome sequencing revealed that the pair of viruses differed only at NA amino acid position 275. We found that the oseltamivir-resistant H1N1/2009 virus was not transmitted efficiently in ferrets via respiratory droplets (0/2), while it retained efficient transmission via direct contact (2/2). The sensitive H1N1/2009 virus was efficiently transmitted via both routes (2/2 and 1/2, respectively). The wild-type H1N1/2009 and the resistant mutant appeared to cause a similar disease course in ferrets without apparent attenuation of clinical signs. We compared viral fitness within the host by co-infecting a ferret with oseltamivir-sensitive and -resistant H1N1/2009 viruses and found that the resistant virus showed less growth capability (fitness). The NA of the resistant virus showed reduced substrate-binding affinity and catalytic activity in vitro and delayed initial growth in MDCK and MDCK-SIAT1 cells. These findings may in part explain its less efficient transmission. The fact that the oseltamivir-resistant H1N1/2009 virus retained efficient transmission through direct contact underlines the necessity of continuous monitoring of drug resistance and characterization of possible

  16. A traveling wave of lateral movement coordinates both turning and forward walking in the ferret.

    PubMed

    Kafkafi, N; Golani, I

    1998-06-01

    Relative phase was recently suggested as a key variable for the dynamical modeling of coordination in both quadruped locomotion and undulation swimming in fish. Relative phase analysis has not yet been applied, however, to the behavior of intact, freely moving animals, but only to simplified situations involving restrained animals and humans. In order to investigate relative phase under free movement conditions, we filmed free locomotion of ferrets (Mustella putorius) from below (through a glass floor) and measured the lateral bending along the head, torso, and tail, and the location of the four paws. We introduced an algorithm which extracts the phase (and thus also the relative phase) even when the movements were neither periodic nor symmetric. Our results show that relative phases between segments have preferred values, which are relatively independent of the amplitude, duration, and asymmetry of the movement. In particular, both walking and turning can be explained as modulations of a single pattern: a cephalo-caudal, traveling wave of lateral movement with a wavelength of approximately one length of the body. The relative phase between movements of adjacent segments is similar when the body is in S shape (i.e., when walking forward), or C shape (i.e., when turning). The movements of the paws in the horizontal plane can also be considered as part of this traveling wave. Our findings suggest that the concept of traveling waves of lateral bending, as found in the locomotion of undulating fish, can be generalized in two ways: (i) by considering the axis around which the movement is centered, it applies not only to forward locomotion, but also to turning: (ii) by incorporating the position of the paws, it applies also to the movement of quadrupeds. Our findings suggest that the relative phase, once it is generalized to asymmetric and quasi-periodic movement, is suitable for modeling coordination patterns under free movement conditions. PMID:9711818

  17. A Transient Metabolic Recovery from Early Life Glucose Intolerance in Cystic Fibrosis Ferrets Occurs During Pancreatic Remodeling.

    PubMed

    Yi, Yaling; Sun, Xingshen; Gibson-Corley, Katherine; Xie, Weiliang; Liang, Bo; He, Nan; Tyler, Scott R; Uc, Aliye; Philipson, Louis H; Wang, Kai; Hara, Manami; Ode, Katie Larson; Norris, Andrew W; Engelhardt, John F

    2016-05-01

    Cystic fibrosis (CF)-related diabetes in humans is intimately related to exocrine pancreatic insufficiency, yet little is known about how these 2 disease processes simultaneously evolve in CF. In this context, we examined CF ferrets during the evolution of exocrine pancreatic disease. At 1 month of age, CF ferrets experienced a glycemic crisis with spontaneous diabetic-level hyperglycemia. This occurred during a spike in pancreatic inflammation that was preceded by pancreatic fibrosis and loss of β-cell mass. Surprisingly, there was spontaneous normalization of glucose levels at 2-3 months, with intermediate hyperglycemia thereafter. Mixed meal tolerance was impaired at all ages, but glucose intolerance was not detected until 4 months. Insulin secretion in response to hyperglycemic clamp and to arginine was impaired. Insulin sensitivity, measured by euglycemic hyperinsulinemic clamp, was normal. Pancreatic inflammation rapidly diminished after 2 months of age during a period where β-cell mass rose and gene expression of islet hormones, peroxisome proliferator-activated receptor-γ, and adiponectin increased. We conclude that active CF exocrine pancreatic inflammation adversely affects β-cells but is followed by islet resurgence. We predict that very young humans with CF may experience a transient glycemic crisis and postulate that pancreatic inflammatory to adipogenic remodeling may facilitate islet adaptation in CF. PMID:26862997

  18. Vaccination as a potential means to prevent plague in black-footed ferrets:progress and continuing challenges

    USGS Publications Warehouse

    Rocke, T.E.; Nol, P.; Marinari, P.E.; Kreeger, J.S.; Smith, S.R.; Andrews, G.P.; Friedlander, A.W.

    2006-01-01

    received a placebo by the same route. Two weeks after the second immunization, mean antibody titers to Y. pestis F1 and V antigens were measured and found to be significantly higher in vaccinates than their preimmunization values (P < 0.0001) and significantly higher than the control values (P < 0.0001). Six months postimmunization, 16 vaccinates and eight controls were challenged with approximately 8,000 colony forming units of virulent plague by subcutaneous inoculation. Eleven of 16 vaccinates (69 percent) survived with no ill effects whereas all eight control animals died within 3a??6 days. Two months later, the 11 surviving vaccinates were challenged again by ingestion of a plague-infected mouse. None of the animals showed any ill effects and all survived. In contrast, seven control ferrets fed infected mice died within 2a??4 days, including one animal that did not actually ingest the mouse but was likely exposed to it. This study demonstrates that immunization of ferrets with the recombinant F1-V fusion protein can induce significant antibody responses and reduce their susceptibility to plague infection.

  19. New reassortant and enzootic European swine influenza viruses transmit efficiently through direct contact in the ferret model

    PubMed Central

    Fabrizio, Thomas P.; Yoon, Sun-Woo; Hansen, Mette Sif; Webby, Richard J.; Larsen, Lars E.

    2015-01-01

    The reverse zoonotic events that introduced the 2009 pandemic influenza virus into pigs have drastically increased the diversity of swine influenza viruses in Europe. The pandemic potential of these novel reassortments is still unclear, necessitating enhanced surveillance of European pigs with additional focus on risk assessment of these new viruses. In this study, four European swine influenza viruses were assessed for their zoonotic potential. Two of the four viruses were enzootic viruses of subtype H1N2 (with avian-like H1) and H3N2, and two were new reassortants, one with avian-like H1 and human-like N2 and one with 2009 pandemic H1 and swine-like N2. All viruses replicated to high titres in nasal wash and nasal turbinate samples from inoculated ferrets and transmitted efficiently by direct contact. Only the H3N2 virus transmitted to naïve ferrets via the airborne route. Growth kinetics using a differentiated human bronchial epithelial cell line showed that all four viruses were able to replicate to high titres. Further, the viruses revealed preferential binding to the 2,6-α-silalylated glycans and investigation of the antiviral susceptibility of the viruses revealed that all were sensitive to neuraminidase inhibitors. These findings suggested that these viruses have the potential to infect humans and further underline the need for continued surveillance as well as biological characterization of new influenza A viruses. PMID:25701826

  20. Virulence of a novel reassortant canine H3N2 influenza virus in ferret, dog and mouse models.

    PubMed

    Lyoo, Kwang-Soo; Na, Woonsung; Yeom, Minjoo; Jeong, Dae-Gwin; Kim, Chang-Ung; Kim, Jeong-Ki; Song, Daesub

    2016-07-01

    An outbreak of a canine influenza virus (CIV) H3N2 reassortant derived from pandemic (pdm) H1N1 and CIV H3N2 in companion animals has underscored the urgent need to monitor CIV infections for potential zoonotic transmission of influenza viruses to humans. In this study, we assessed the virulence of a novel CIV H3N2 reassortant, VC378, which was obtained from a dog that was coinfected with pdm H1N1 and CIV H3N2, in ferrets, dogs, and mice. Significantly enhanced virulence of VC378 was demonstrated in mice, although the transmissibility and pathogenicity of VC378 were similar to those of classical H3N2 in ferrets and dogs. This is notable because mice inoculated with an equivalent dose of classical CIV H3N2 showed no clinical signs and no lethality. We found that the PA and NS gene segments of VC378 were introduced from pdmH1N1, and these genes included the amino acid substitutions PA-P224S and NS-I123V, which were previously found to be associated with increased virulence in mice. Thus, we speculate that the natural reassortment between pdm H1N1 and CIV H3N2 can confer virulence and that continuous surveillance is needed to monitor the evolution of CIV in companion animals. PMID:27138550

  1. Glycosylations in demilunar and central acinar cells of the submandibular salivary gland of ferret investigated by lectin histochemistry.

    PubMed

    Triantafyllou, Asterios; Fletcher, David; Scott, John

    2004-09-01

    'Resting' submandibular salivary glands obtained post-mortem from mature ferrets of both sexes were examined here. The binding patterns of labelled lectins applied to paraffin sections of tissue slivers fixed in an aldehyde-HgCl2 mixture and the effects of pretreatment procedures on the results were assessed lightmicroscopically. Lectins with affinity for terminal GalNAc residues (DBA, SBA) bound preferentially to demilunar acinar cells which were also strongly reactive with Fuc-directed UEA I. In contrast, lectins with affinity for neuraminic acid (SNA, WGA) bound to central acinar cells where consistent binding of DBA and SNA occurred only after neuraminidase digestion, and variation in the binding of UEA I was seen. The reactivities corresponded with the distribution of secretory granules, but staining in Golgi-like areas occurred in central acinar cells with PNA lectin. The results suggest that glycosylations are more advanced in central than demilunar acinar cells of the ferret submandibular gland. Possibly demilunar and central acinar cells reflect phenotypic changes of a single secretory cell, the 'central' acinar phenotype being influenced by incorporation of neuraminic acid in glycoprotein side chains and by increased Golgi activity.

  2. New reassortant and enzootic European swine influenza viruses transmit efficiently through direct contact in the ferret model.

    PubMed

    Fobian, Kristina; Fabrizio, Thomas P; Yoon, Sun-Woo; Hansen, Mette Sif; Webby, Richard J; Larsen, Lars E

    2015-07-01

    The reverse zoonotic events that introduced the 2009 pandemic influenza virus into pigs have drastically increased the diversity of swine influenza viruses in Europe. The pandemic potential of these novel reassortments is still unclear, necessitating enhanced surveillance of European pigs with additional focus on risk assessment of these new viruses. In this study, four European swine influenza viruses were assessed for their zoonotic potential. Two of the four viruses were enzootic viruses of subtype H1N2 (with avian-like H1) and H3N2, and two were new reassortants, one with avian-like H1 and human-like N2 and one with 2009 pandemic H1 and swine-like N2. All viruses replicated to high titres in nasal wash and nasal turbinate samples from inoculated ferrets and transmitted efficiently by direct contact. Only the H3N2 virus transmitted to naïve ferrets via the airborne route. Growth kinetics using a differentiated human bronchial epithelial cell line showed that all four viruses were able to replicate to high titres. Further, the viruses revealed preferential binding to the 2,6-α-silalylated glycans and investigation of the antiviral susceptibility of the viruses revealed that all were sensitive to neuraminidase inhibitors. These findings suggested that these viruses have the potential to infect humans and further underline the need for continued surveillance as well as biological characterization of new influenza A viruses.

  3. Development of ferret as a human lung cancer model by injecting4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Development of new animal lung cancer models that are relevant to human lung carcinogenesis is important for lung cancer research. Previously we have shown the induction of lung tumor in ferrets (Mustela putorius furo) exposed to both tobacco smoke and a tobacco carcinogen (4-(N-methyl-N-nitrosamino...

  4. Comparison of the Levels of Infectious Virus in Respirable Aerosols Exhaled by Ferrets Infected with Influenza Viruses Exhibiting Diverse Transmissibility Phenotypes

    PubMed Central

    Gustin, Kortney M.; Katz, Jacqueline M.; Tumpey, Terrence M.

    2013-01-01

    Influenza viruses pose a major public health burden to communities around the world by causing respiratory infections that can be highly contagious and spread rapidly through the population. Despite extensive research on influenza viruses, the modes of transmission occurring most often among humans are not entirely clear. Contributing to this knowledge gap is the lack of an understanding of the levels of infectious virus present in respirable aerosols exhaled from infected hosts. Here, we used the ferret model to evaluate aerosol shedding patterns and measure the amount of infectious virus present in exhaled respirable aerosols. By comparing these parameters among a panel of human and avian influenza viruses exhibiting diverse respiratory droplet transmission efficiencies, we are able to report that ferrets infected by highly transmissible influenza viruses exhale a greater number of aerosol particles and more infectious virus within respirable aerosols than ferrets infected by influenza viruses that do not readily transmit. Our findings improve our understanding of the ferret transmission model and provide support for the potential for influenza virus aerosol transmission. PMID:23658443

  5. A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

    SciTech Connect

    Joseph, Tomy; McAuliffe, Josephine; Lu, Bin; Vogel, Leatrice; Swayne, David; Jin, Hong; Kemble, George; Subbarao, Kanta

    2008-08-15

    The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials.

  6. Experimental oral immunization of ferret badgers (Melogale moschata) with a recombinant canine adenovirus vaccine CAV-2-E3Δ-RGP and an attenuated rabies virus SRV9.

    PubMed

    Zhao, Jinghui; Liu, Ye; Zhang, Shoufeng; Fang, Lijun; Zhang, Fei; Hu, Rongliang

    2014-04-01

    Ferret badgers (Melogale moschata) are a major reservoir of rabies virus in southeastern China. Oral immunization has been shown to be a practical method for wildlife rabies management in Europe and North America. Two groups of 20 ferret badgers were given a single oral dose of a recombinant canine adenovirus-rabies vaccine, CAV-2-E3Δ-RGP, or an experimental attenuated rabies virus vaccine, SRV9. At 21 days, all ferret badgers had seroconverted, with serum virus-neutralizing antibodies ranging from 0.1 to 4.5 IU/mL. Titers were >0.50 IU/mL (an acceptable level) in 17/20 and 16/20 animals receiving CAV-2-E3Δ-RGP or SRV9, respectively. The serologic results indicate that the recombinant CAV-2-E3Δ-RGP is at least as effective as the attenuated rabies virus vaccine. Both may be considered for additional research as oral rabies vaccine candidates for ferret badgers.

  7. Tobacco carcinogen induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation.

    PubMed

    Aizawa, Koichi; Liu, Chun; Tang, Sanyuan; Veeramachaneni, Sudipta; Hu, Kang-Quan; Smith, Donald E; Wang, Xiang-Dong

    2016-09-01

    Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carcinoma (HCC). In the present study, we investigated whether the tobacco carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lesions in both lungs and livers of ferrets with or without lycopene intervention. Male ferrets (6 groups, n = 8-10) were treated either with NNK (50 mg/kg BW, i.p., once a month for four consecutive months) or saline with or without dietary lycopene supplementation (2.2 and 6.6 mg/kg BW/day, respectively) for 26 weeks. Results demonstrate that NNK exposure results in higher incidences of lung tumors, HCC and steatohepatitis (which is characterized by severe inflammatory cell infiltration with concurrent fat accumulation in liver, hepatocellular ballooning degeneration and increased NF-κB expression), as well as elevations in bilirubin and AST levels in ferrets. Lycopene supplementation at two doses prevented NNK-induced expressions of α7 nicotinic acetylcholine receptor in the lung and NF-κB and CYP2E1 in the liver and attenuated the NNK-induced mortality and pathological lesions in both the lungs and livers of ferrets. The present study provided strong experimental evidence that the tobacco carcinogen NNK can induce both HCC and steatohepatitis in the ferrets and can be a useful model for studying tobacco carcinogen-associated NAFLD and liver cancer. Furthermore, lycopene could provide potential benefits against smoke carcinogen-induced pulmonary and hepatic injury. PMID:27116542

  8. Plant-derived H7 VLP vaccine elicits protective immune response against H7N9 influenza virus in mice and ferrets.

    PubMed

    Pillet, S; Racine, T; Nfon, C; Di Lenardo, T Z; Babiuk, S; Ward, B J; Kobinger, G P; Landry, N

    2015-11-17

    In March 2013, the Chinese Centre for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A H7N9 virus. Infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. The risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. Here, we describe the rapid (19 days) development of a plant-derived VLP vaccine based on the hemagglutinin sequence of influenza H7N9 A/Hangzhou/1/2013. The immunogenicity of the H7 VLP vaccine was assessed in mice and ferrets after one or two intramuscular dose(s) with and without adjuvant (alum or GLA-SE™). In ferrets, we also measured H7-specific cell-mediated immunity. The mice and ferrets were then challenged with H7N9 A/Anhui/1/2013 influenza virus. A single immunization with the adjuvanted vaccine elicited a strong humoral response and protected mice against an otherwise lethal challenge. Two doses of unadjuvanted vaccine significantly increased humoral response and resulted in 100% protection with significant reduction of clinical signs leading to nearly asymptomatic infections. In ferrets, a single immunization with the alum-adjuvanted H7 VLP vaccine induced strong humoral and CMI responses with antigen-specific activation of CD3(+) T cells. Compared to animals injected with placebo, ferrets vaccinated with alum-adjuvanted vaccine displayed no weight loss during the challenge. Moreover, the vaccination significantly reduced the viral load in lungs and nasal washes 3 days after the infection. This candidate plant-made H7 vaccine therefore induced protective responses after either one adjuvanted or two unadjuvanted doses. Studies are currently ongoing to better characterize the immune response elicited by the plant-derived VLP vaccines. Regardless, these data are very promising for the rapid production of an immunogenic and protective vaccine against

  9. Isolation of differentially expressed cDNAs during ferret tracheal development: application of differential display PCR.

    PubMed

    Sehgal, A; Presente, A; Dudus, L; Engelhardt, J F

    1996-01-01

    The technique of differential display polymerase chain reaction (DD-PCR) was used to identify cDNA sequences, which are temporally expressed during ferret tracheal airway development. Such differentially expressed cDNAs may ultimately prove to be useful markers in elucidating mechanisms of epithelial differentiation and submucosal gland development in the airway. Using two sets of oligonucleotide primers 15 differentially amplified cDNAs were isolated by comparative reverse transcriptase (RT) PCR of 6-h and 3-day postnatal tracheal poly-A mRNA. In situ hybridization was used to assess the reliability of this method and confirm the differential mRNA expression patterns of cloned cDNAs. Results of in situ hybridization analysis demonstrated that 10 of the 15 cDNA sequences gave a temporally regulated pattern of expression, which was concordant with that of the differential display. Furthermore, sequence analysis of the 15 isolated cDNAs revealed that the majority of clones were amplified from two inverted decamer primers. These findings demonstrate the lack of poly-T priming in the differential display reaction, which suggests that this method may yield substantially more information regarding the coding sequence of cloned genes. In support of this observation, 6 of the 15 cDNA sequences contained one complete open reading frame. Although the majority of cDNAs demonstrated no homology to sequence data bases at the DNA or amino acid level, clone FT-4, which demonstrated a differential expression pattern limited to 3-day tracheal time points, was composed of a 10-amino acid repeat domain that was structurally similar to neuropeptide anthoRFamide and barley D hordein seed protein. A second interesting clone, FT-3, demonstrated an infrequent pattern of expression within a subset of epithelial cells limited to early developmental time points (6 h) and was dramatically reduced by 3 days postnatally. Several additional clones with no homologies to previously cloned genes

  10. Sedimentology of box cores from the Cap-Ferret Canyon area (Bay of Biscay)

    NASA Astrophysics Data System (ADS)

    Cremer, Michel; Weber, Olivier; Jouanneau, Jean-Marie

    1999-10-01

    Sedimentological and geochemical investigations of 45 box cores collected in various morphological settings of the Cap-Ferret Canyon (Bay of Biscay) are presented to document accurately present-day sedimentary processes on the eastern Atlantic continental slope. The magnitude and variations through time and space of the canyon's channelling or sinking effect on fine-grained particles behaviour in comparison with sediment flux across the continental margin was particularly considered and discussed: 1. All the parameters (grain-size, carbonate and water content, major and trace elements), measured both in surface sediment and downcore, demonstrate that the characteristics at the sediment interface vary with water depth and with the morphological setting. 2. Surface sediment is generally coarser-grained, more terrigenous and deposited at higher rate in the canyon than outside. The terrigenous particle supply must be preferentially directed and trapped within the canyon's depression due to present-day dynamic conditions. 3. The downcore gradients reflected in grain-size variations yield information on settling processes. The coarse-grained population has the characteristics of a winnowed sediment similar to those on the outer shelf, while the fine-grained population has grain-size spectra very similar to the present-day fine-grained suspensions. 4. The carbonate particles are partly derived from direct pelagic production (distinct grain-size distribution) and, like terrigenous grains, are partly reworked (similar downslope decrease in the coarse grained fraction). The relatively low CaCO 3 content observed in the canyon, and its downward increase up to values observed at shallower depths, may result from a channelling of terrigenous suspensions within the canyon. 5. At the present high sea-level stand, the canyon should become a trap for sediments without much gravity remobilisation, as indicated by a lack of sedimentary structures in box cores. However, a simple

  11. A Live Attenuated Equine H3N8 Influenza Vaccine Is Highly Immunogenic and Efficacious in Mice and Ferrets

    PubMed Central

    Baz, Mariana; Paskel, Myeisha; Matsuoka, Yumiko; Zengel, James; Cheng, Xing; Treanor, John J.; Jin, Hong

    2014-01-01

    ABSTRACT Equine influenza viruses (EIV) are responsible for rapidly spreading outbreaks of respiratory disease in horses. Although natural infections of humans with EIV have not been reported, experimental inoculation of humans with these viruses can lead to a productive infection and elicit a neutralizing antibody response. Moreover, EIV have crossed the species barrier to infect dogs, pigs, and camels and therefore may also pose a threat to humans. Based on serologic cross-reactivity of H3N8 EIV from different lineages and sublineages, A/equine/Georgia/1/1981 (eq/GA/81) was selected to produce a live attenuated candidate vaccine by reverse genetics with the hemagglutinin and neuraminidase genes of the eq/GA/81 wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 (H2N2) vaccine donor virus, which is the backbone of the licensed seasonal live attenuated influenza vaccine. In both mice and ferrets, intranasal administration of a single dose of the eq/GA/81 ca vaccine virus induced neutralizing antibodies and conferred complete protection from homologous wt virus challenge in the upper respiratory tract. One dose of the eq/GA/81 ca vaccine also induced neutralizing antibodies and conferred complete protection in mice and nearly complete protection in ferrets upon heterologous challenge with the H3N8 (eq/Newmarket/03) wt virus. These data support further evaluation of the eq/GA/81 ca vaccine in humans for use in the event of transmission of an equine H3N8 influenza virus to humans. IMPORTANCE Equine influenza viruses have crossed the species barrier to infect other mammals such as dogs, pigs, and camels and therefore may also pose a threat to humans. We believe that it is important to develop vaccines against equine influenza viruses in the event that an EIV evolves, adapts, and spreads in humans, causing disease. We generated a live attenuated H3N8 vaccine candidate and demonstrated that the vaccine was immunogenic and

  12. A cationic liposome-DNA complexes adjuvant (JVRS-100) enhances the immunogenicity and cross-protective efficacy of pre-pandemic influenza A (H5N1) vaccine in ferrets.

    PubMed

    Liu, Feng; Sun, Xiangjie; Fairman, Jeffery; Lewis, David B; Katz, Jacqueline M; Levine, Min; Tumpey, Terrence M; Lu, Xiuhua

    2016-05-01

    Influenza A (H5N1) viruses continue to pose a public health threat. As inactivated H5N1 vaccines are poorly immunogenic, adjuvants are needed to improve the immunogenicity of H5N1 vaccine in humans. Here, we investigated the immunogenicity and cross-protective efficacy in ferrets of a clade 2.2-derived vaccine with addition of JVRS-100, an adjuvant consisting of cationic liposome-DNA complexes (CLDC). After the first vaccination, significantly higher levels of hemagglutination-inhibition (HAI) and neutralizing antibody titers were detected in ferrets immunized with adjuvanted vaccine compared to unadjuvanted vaccine. Following a second dose of adjuvanted vaccine, HAI antibody titers of ≥ 40 were detected against viruses from multiple H5N1 clades. HAI antibodies against newly isolated H5N2 and H5N8 viruses were also augmented by JVRS-100. Ferrets were challenged with a heterologous H5N1 virus. All ferrets that received two doses of adjuvanted vaccine exhibited mild illness, significantly reduced nasal wash virus titers and protection from lethal challenge. In contrast, ferrets that received unadjuvanted vaccine showed greater weight loss, high viral titers and 3 of 6 animals succumbed to the lethal challenge. Our results indicate that the addition of JVRS-100 to H5N1 vaccine enhanced immunogenicity and cross-protection against lethal H5N1 virus disease in ferrets. JVRS-100 warrants further investigation as a potential adjuvant for influenza vaccines. PMID:26967975

  13. The "ferret out the lesbians" legend: Johnnie Phelps, General Eisenhower, and the power and politics of myth.

    PubMed

    Knaff, Donna

    2009-01-01

    The most famous lesbian story to come out of World War II was told by Women's Army Corps (WAC) soldier Nell "Johnnie" Phelps, who claimed to have been given an order by General Dwight D. Eisenhower to "ferret out the lesbians" in her WAC detachment. This article backgrounds her story with history of women in the WAC in World War II and recounts the narrative as it appears in transcripts of Phelps' oral history and in other publications featuring it. It analyzes the public discourse around Phelps' account and its disproval and examines the ways the story has been used for political, historical, community, and personal aims since the oral history was taken in 1982.

  14. H1N1, but Not H3N2, Influenza A Virus Infection Protects Ferrets from H5N1 Encephalitis

    PubMed Central

    Wang, Guoji; Carter, Donald M.; Crevar, Corey J.; Ross, Ted M.; Wiley, Clayton A.

    2014-01-01

    ABSTRACT Seasonal influenza causes substantial morbidity and mortality because of efficient human-to-human spread. Rarely, zoonotic strains of influenza virus spread to humans, where they have the potential to mediate new pandemics with high mortality. We studied systemic viral spread after intranasal infection with highly pathogenic avian influenza virus (H5N1 [A/Viet Nam/1203/2004]) in ferrets with or without prior pandemic H1N1pdm09 (A/Mexico/4108/2009) or H3N2 (A/Victoria/361/2011) infection. After intranasal challenge with H5N1 influenza virus, naive ferrets rapidly succumbed to systemic infection. Animals challenged with H5N1 influenza virus greater than 3 months after recovering from an initial H1N1pdm09 infection survived H5N1 virus challenge and cleared virus from the respiratory tract 4 days after infection. However, a prolonged low-level infection of hematopoietic elements in the small bowel lamina propria, liver, and spleen was present for greater than 2 weeks postinfection, raising the potential for reassortment of influenza genes in a host infected with multiple strains of influenza. Animals previously infected with an H3N2 influenza virus succumbed to systemic disease and encephalitis after H5N1 virus challenge. These results indicate prior infection with different seasonal influenza strains leads to radically different protection from H5N1 challenge and fatal encephalitis. IMPORTANCE Seasonal influenza is efficiently transmitted from human to human, causing substantial morbidity and mortality. Rarely, zoonotic strains of influenza virus spread to humans, where they have the potential to mediate new pandemics with high mortality. Infection of naive ferrets with H5N1 avian influenza virus causes a rapid and lethal systemic disease. We studied systemic H5N1 viral spread after infection of ferrets with or without prior exposure to either of two seasonal influenza virus strains, H1N1 and H3N2. Ferrets previously infected with H1N1 survive H5N1 challenge

  15. Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets.

    PubMed

    Yen, Hui-Ling; Liang, Chi-Hui; Wu, Chung-Yi; Forrest, Heather L; Ferguson, Angela; Choy, Ka-Tim; Jones, Jeremy; Wong, Diana Dik-Yan; Cheung, Peter Pak-Hang; Hsu, Che-Hsiung; Li, Olive T; Yuen, Kit M; Chan, Renee W Y; Poon, Leo L M; Chan, Michael C W; Nicholls, John M; Krauss, Scott; Wong, Chi-Huey; Guan, Yi; Webster, Robert G; Webby, Richard J; Peiris, Malik

    2011-08-23

    A novel reassortant derived from North American triple-reassortant (TRsw) and Eurasian swine (EAsw) influenza viruses acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. To identify molecular determinants that allowed efficient transmission of the pandemic H1N1 virus among humans, we evaluated the direct-contact and respiratory-droplet transmissibility in ferrets of representative swine influenza viruses of different lineages obtained through a 13-y surveillance program in southern China. Whereas all viruses studied were transmitted by direct contact with varying efficiency, respiratory-droplet transmissibility (albeit inefficient) was observed only in the TRsw-like A/swine/Hong Kong/915/04 (sw915) (H1N2) virus. The sw915 virus had acquired the M gene derived from EAsw and differed from the gene constellation of the pandemic H1N1 virus by the neuraminidase (NA) gene alone. Glycan array analysis showed that pandemic H1N1 virus A/HK/415742/09 (HK415742) and sw915 possess similar receptor-binding specificity and affinity for α2,6-linked sialosides. Sw915 titers in differentiated normal human bronchial epithelial cells and in ferret nasal washes were lower than those of HK415742. Introducing the NA from pandemic HK415742 into sw915 did not increase viral replication efficiency but increased respiratory-droplet transmissibility, despite a substantial amino acid difference between the two viruses. The NA of the pandemic HK415742 virus possessed significantly higher enzyme activity than that of sw915 or other swine influenza viruses. Our results suggest that a unique gene constellation and hemagglutinin-neuraminidase balance play a critical role in acquisition of efficient and sustained human-to-human transmissibility.

  16. Hemagglutinin–neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferrets

    PubMed Central

    Yen, Hui-Ling; Liang, Chi-Hui; Wu, Chung-Yi; Forrest, Heather L.; Ferguson, Angela; Choy, Ka-Tim; Jones, Jeremy; Wong, Diana Dik-Yan; Cheung, Peter Pak-Hang; Hsu, Che-Hsiung; Li, Olive T.; Yuen, Kit M.; Chan, Renee W. Y.; Poon, Leo L. M.; Chan, Michael C. W.; Nicholls, John M.; Krauss, Scott; Wong, Chi-Huey; Guan, Yi; Webster, Robert G.; Webby, Richard J.; Peiris, Malik

    2011-01-01

    A novel reassortant derived from North American triple-reassortant (TRsw) and Eurasian swine (EAsw) influenza viruses acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. To identify molecular determinants that allowed efficient transmission of the pandemic H1N1 virus among humans, we evaluated the direct-contact and respiratory-droplet transmissibility in ferrets of representative swine influenza viruses of different lineages obtained through a 13-y surveillance program in southern China. Whereas all viruses studied were transmitted by direct contact with varying efficiency, respiratory-droplet transmissibility (albeit inefficient) was observed only in the TRsw-like A/swine/Hong Kong/915/04 (sw915) (H1N2) virus. The sw915 virus had acquired the M gene derived from EAsw and differed from the gene constellation of the pandemic H1N1 virus by the neuraminidase (NA) gene alone. Glycan array analysis showed that pandemic H1N1 virus A/HK/415742/09 (HK415742) and sw915 possess similar receptor-binding specificity and affinity for α2,6-linked sialosides. Sw915 titers in differentiated normal human bronchial epithelial cells and in ferret nasal washes were lower than those of HK415742. Introducing the NA from pandemic HK415742 into sw915 did not increase viral replication efficiency but increased respiratory-droplet transmissibility, despite a substantial amino acid difference between the two viruses. The NA of the pandemic HK415742 virus possessed significantly higher enzyme activity than that of sw915 or other swine influenza viruses. Our results suggest that a unique gene constellation and hemagglutinin–neuraminidase balance play a critical role in acquisition of efficient and sustained human-to-human transmissibility. PMID:21825167

  17. Recombinant Canine Distemper Virus Strain Snyder Hill Expressing Green or Red Fluorescent Proteins Causes Meningoencephalitis in the Ferret

    PubMed Central

    Ludlow, M.; Nguyen, D. T.; Silin, D.; Lyubomska, O.; de Vries, R. D.; von Messling, V.; McQuaid, S.; De Swart, R. L.

    2012-01-01

    The propensity of canine distemper virus (CDV) to spread to the central nervous system is one of the primary features of distemper. Therefore, we developed a reverse genetics system based on the neurovirulent Snyder Hill (SH) strain of CDV (CDVSH) and show that this virus rapidly circumvents the blood-brain and blood-cerebrospinal fluid (CSF) barriers to spread into the subarachnoid space to induce dramatic viral meningoencephalitis. The use of recombinant CDVSH (rCDVSH) expressing enhanced green fluorescent protein (EGFP) or red fluorescent protein (dTomato) facilitated the sensitive pathological assessment of routes of virus spread in vivo. Infection of ferrets with these viruses led to the full spectrum of clinical signs typically associated with distemper in dogs during a rapid, fatal disease course of approximately 2 weeks. Comparison with the ferret-adapted CDV5804P and the prototypic wild-type CDVR252 showed that hematogenous infection of the choroid plexus is not a significant route of virus spread into the CSF. Instead, viral spread into the subarachnoid space in rCDVSH-infected animals was triggered by infection of vascular endothelial cells and the hematogenous spread of virus-infected leukocytes from meningeal blood vessels into the subarachnoid space. This resulted in widespread infection of cells of the pia and arachnoid mater of the leptomeninges over large areas of the cerebral hemispheres. The ability to sensitively assess the in vivo spread of a neurovirulent strain of CDV provides a novel model system to study the mechanisms of virus spread into the CSF and the pathogenesis of acute viral meningitis. PMID:22553334

  18. The effect of acidosis on the interval-force relation and mechanical restitution in ferret papillary muscle.

    PubMed

    McCall, E; Orchard, C H

    1991-01-01

    1. The effect of a respiratory acidosis on the interval-force relation and on mechanical restitution was investigated in ferret papillary muscles. 2. Acidosis (pH 6.85) decreased developed force over a range of stimulation frequencies (1.0.06 Hz); the percentage decrease was greatest at the lowest stimulation frequencies. Qualitatively similar effects of acidosis on developed force were observed in the presence of the sarcoplasmic reticulum (SR) inhibitor ryanodine. 3. Mechanical restitution curves were constructed by interpolating extra-systoles at different test intervals following a train of steady-state beats. Mechanical restitution in ferret papillary muscle was triphasic: an initial, rapid, exponential increase in force with test intervals to 2 s, a further increase with test intervals between 60 and 90 s and then a slow decline, with a plateau at about 30 min (0.33 Hz, 30 degrees C). 4. Acidosis slowed the initial phase of mechanical restitution. The degree of slowing depended on the steady-state stimulation frequency, being greatest at low frequencies. 5. Inhibition of the SR abolished the initial phase of mechanical restitution, suggesting that this phase depends on Ca2+ release from the SR. 6. The strength of the first contraction after the extra-systole varied inversely with the size of the extra-systole under all conditions studied. 7. It is concluded that acidosis may inhibit the SR by altering the time required for Ca2+ recycling between contractions. This effect may alter Ca2+ release from the SR during acidosis, and may underlie the mechanical alternans (the alternation of small and large contractions) that can occur during acidosis.

  19. An unidentified filarial species and its impact on fitness in wild populations of the black-footed ferret (Mustela nigripes).

    PubMed

    Wisely, Samantha M; Howard, JoGayle; Williams, Steven A; Bain, Odile; Santymire, Rachel M; Bardsley, Katherine D; Williams, Elizabeth S

    2008-01-01

    Disease can threaten the restoration of endangered species directly by substantially decreasing host survival or indirectly via incremental decreases in survival and reproduction. During a biomedical survey of reintroduced populations of the highly endangered black-footed ferret from 2002 to 2005, microfilariae discovered in the blood were putatively identified as Dirofilaria immitis, and widespread screening was initiated using a commercially available antigen-based ELISA test. A subset of animals (n = 16) was screened for D. immitis using a highly sensitive PCR-based assay. Microfilariae were also molecularly and morphologically characterized. Of 198 animals at six reintroduction sites, 12% had positive results using the ELISA test. No antigen-positive animals which were screened via PCR (n = 11) had positive PCR results, and all antigen-positive animals (n = 24) were asymptomatic. No significant differences were found in body mass of antigen-positive (male: 1223 +/- 82 g [mean +/- SD], female: 726 +/- 75 g) vs. antigen-negative (male: 1,198 +/- 119 g, female: 710 +/- 53 g) individuals (P = 0.4). Antigen prevalence was lower in juveniles (3%) than adults (12%; P = 0.03), and higher in in situ, captive-reared individuals (33%) than wild-born individuals (10%; P = 0.005). Morphologic analysis of microfilariae revealed they were neither D. immitis nor any other previously characterized North American species. PCR amplification of the 5S spacer region of rDNA revealed that the filarial sequence shared only 76% identity with D. immitis. This previously unidentified filarial sequence was present in all antigen positive animals (11 of 11 tested). It appears that black-footed ferrets were infected with a previously undescribed species of filaria whose antigen cross-reacted with the ELISA assay, although further analysis is needed to make a conclusive statement. Nonetheless, this previously undescribed filaria does not appear to threaten recovery for this highly

  20. Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

    PubMed Central

    Pascua, Philippe Noriel Q.; Song, Min-Suk; Lee, Jun Han; Baek, Yun Hee; Kwon, Hyeok-il; Park, Su-Jin; Choi, Eun Hye; Lim, Gyo-Jin; Lee, Ok-Jun; Kim, Si-Wook; Kim, Chul-Joong; Sung, Moon Hee; Kim, Myung Hee; Yoon, Sun-Woo; Govorkova, Elena A.; Webby, Richard J.; Webster, Robert G.; Choi, Young-Ki

    2012-01-01

    Efficient worldwide swine surveillance for influenza A viruses is urgently needed; the emergence of a novel reassortant pandemic H1N1 (pH1N1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. We used the ferret model to assess the pathogenicity and transmissibility of predominant Korean triple-reassortant swine (TRSw) H1N2 and H3N2 influenza viruses genetically related to North American strains. Although most of the TRSw viruses were moderately pathogenic, one [A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within 10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets. Although molecular analysis did not reveal known virulence markers, the Sw/1204 virus acquired mutations in hemagglutinin (HA) (Asp-225-Gly) and neuraminidase (NA) (Ser-315-Asn) proteins during the single ferret passage. The contact-Sw/1204 virus became more virulent in mice, replicated efficiently in vitro, extensively infected human lung tissues ex vivo, and maintained its ability to replicate and transmit in swine. Reverse-genetics studies further indicated that the HA225G and NA315N substitutions contributed substantially in altering virulence and transmissibility. These findings support the continuing threat of some field TRSw viruses to human and animal health, reviving concerns on the capacity of pigs to create future pandemic viruses. Apart from warranting continued and enhanced global surveillance, this study also provides evidence on the emerging roles of HA225G and NA315N as potential virulence markers in mammals. PMID:23019374

  1. Recombinant virus-like particles elicit protective immunity against avian influenza A(H7N9) virus infection in ferrets.

    PubMed

    Liu, Ye V; Massare, Michael J; Pearce, Melissa B; Sun, Xiangjie; Belser, Jessica A; Maines, Taronna R; Creager, Hannah M; Glenn, Gregory M; Pushko, Peter; Smith, Gale E; Tumpey, Terrence M

    2015-04-27

    In March 2013, diagnosis of the first reported case of human infection with a novel avian-origin influenza A(H7N9) virus occurred in eastern China. Most human cases have resulted in severe respiratory illness and, in some instances, death. Currently there are no licensed vaccines against H7N9 virus, which continues to cause sporadic human infections. Recombinant virus-like particles (VLPs) have been previously shown to be safe and effective vaccines for influenza. In this study, we evaluated the immunogenicity and protective efficacy of a H7N9 VLP vaccine in the ferret challenge model. Purified recombinant H7N9 VLPs morphologically resembled influenza virions and elicited high-titer serum hemagglutination inhibition (HI) and neutralizing antibodies specific for A/Anhui/1/2013 (H7N9) virus. H7N9 VLP-immunized ferrets subsequently challenged with homologous virus displayed reductions in fever, weight loss, and virus shedding compared to these parameters in unimmunized control ferrets. H7N9 VLP was also effective in protecting against lung and tracheal infection. The addition of either ISCOMATRIX or Matrix-M1 adjuvant improved immunogenicity and protection of the VLP vaccine against H7N9 virus. These results provide support for the development of a safe and effective human VLP vaccine with potent adjuvants against avian influenza H7N9 virus with pandemic potential. PMID:25772674

  2. Matrix-M Adjuvated Seasonal Virosomal Influenza Vaccine Induces Partial Protection in Mice and Ferrets against Avian H5 and H7 Challenge.

    PubMed

    Cox, Freek; Roos, Anna; Hafkemeijer, Nicole; Baart, Matthijs; Tolboom, Jeroen; Dekking, Liesbeth; Stittelaar, Koert; Goudsmit, Jaap; Radošević, Katarina; Saeland, Eirikur

    2015-01-01

    There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV) adjuvated with the saponin-based adjuvant Matrix-M (MM) can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak. PMID:26402787

  3. H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets.

    PubMed

    de Jonge, Jørgen; Isakova-Sivak, Irina; van Dijken, Harry; Spijkers, Sanne; Mouthaan, Justin; de Jong, Rineke; Smolonogina, Tatiana; Roholl, Paul; Rudenko, Larisa

    2016-05-01

    Avian influenza viruses continue to cross the species barrier, and if such viruses become transmissible among humans, it would pose a great threat to public health. Since its emergence in China in 2013, H7N9 has caused considerable morbidity and mortality. In the absence of a universal influenza vaccine, preparedness includes development of subtype-specific vaccines. In this study, we developed and evaluated in ferrets an intranasal live attenuated influenza vaccine (LAIV) against H7N9 based on the A/Leningrad/134/17/57 (H2N2) cold-adapted master donor virus. We demonstrate that the LAIV is attenuated and safe in ferrets and induces high hemagglutination- and neuraminidase-inhibiting and virus-neutralizing titers. The antibodies against hemagglutinin were also cross-reactive with divergent H7 strains. To assess efficacy, we used an intratracheal challenge ferret model in which an acute severe viral pneumonia is induced that closely resembles viral pneumonia observed in severe human cases. A single- and two-dose strategy provided complete protection against severe pneumonia and prevented virus replication. The protective effect of the two-dose strategy appeared better than the single dose only on the microscopic level in the lungs. We observed, however, an increased lymphocytic infiltration after challenge in single-vaccinated animals and hypothesize that this a side effect of the model. PMID:26796670

  4. Competitive Fitness of Influenza B Viruses Possessing E119A and H274Y Neuraminidase Inhibitor Resistance-Associated Substitutions in Ferrets.

    PubMed

    Pascua, Philippe Noriel Q; Marathe, Bindumadhav M; Burnham, Andrew J; Vogel, Peter; Webby, Richard J; Webster, Robert G; Govorkova, Elena A

    2016-01-01

    Neuraminidase (NA) inhibitors (NAIs) are the only antiviral drugs recommended for influenza treatment and prophylaxis. Although NAI-resistant influenza B viruses that could pose a threat to public health have been reported in the field, their fitness is poorly understood. We evaluated in ferrets the pathogenicity and relative fitness of reverse genetics (rg)-generated influenza B/Yamanashi/166/1998-like viruses containing E119A or H274Y NA substitutions (N2 numbering). Ferrets inoculated with NAI-susceptible rg-wild-type (rg-WT) or NAI-resistant (rg-E119A or rg-H274Y) viruses developed mild infections. Growth of rg-E119A virus in the nasal cavities was delayed, but the high titers at 3 days post-inoculation (dpi) were comparable to those of the rg-WT and rg-H274Y viruses (3.6-4.1 log10TCID50/mL). No virus persisted beyond 5 dpi and replication did not extend to the trachea or lungs. Positive virus antigen-staining of the nasal turbinate epithelium was intermittent with the rg-WT and rg-H274Y viruses; whereas antigen-staining for the rg-E119A virus was more diffuse. Virus populations in ferrets coinoculated with NAI-susceptible and -resistant viruses (1:1 mixture) remained heterogeneous at 5 dpi but were predominantly rg-WT (>70%). Although the E119A substitution was associated with delayed replication in ferrets, the H274Y substitution did not measurably affect viral growth properties. These data suggest that rg-H274Y has undiminished fitness in single virus inoculations, but neither rg-E119A nor rg-H274Y gained a fitness advantage over rg-WT in direct competition experiments without antiviral drug pressure. Taken together, our data suggest the following order of relative fitness in a ferret animal model: rg-WT > rg-H274Y > rg-E119A. PMID:27466813

  5. Plant-derived H7 VLP vaccine elicits protective immune response against H7N9 influenza virus in mice and ferrets.

    PubMed

    Pillet, S; Racine, T; Nfon, C; Di Lenardo, T Z; Babiuk, S; Ward, B J; Kobinger, G P; Landry, N

    2015-11-17

    In March 2013, the Chinese Centre for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A H7N9 virus. Infection with this virus often caused severe pneumonia and acute respiratory distress syndrome resulting in a case fatality rate >35%. The risk of pandemic highlighted, once again, the need for a more rapid and scalable vaccine response capability. Here, we describe the rapid (19 days) development of a plant-derived VLP vaccine based on the hemagglutinin sequence of influenza H7N9 A/Hangzhou/1/2013. The immunogenicity of the H7 VLP vaccine was assessed in mice and ferrets after one or two intramuscular dose(s) with and without adjuvant (alum or GLA-SE™). In ferrets, we also measured H7-specific cell-mediated immunity. The mice and ferrets were then challenged with H7N9 A/Anhui/1/2013 influenza virus. A single immunization with the adjuvanted vaccine elicited a strong humoral response and protected mice against an otherwise lethal challenge. Two doses of unadjuvanted vaccine significantly increased humoral response and resulted in 100% protection with significant reduction of clinical signs leading to nearly asymptomatic infections. In ferrets, a single immunization with the alum-adjuvanted H7 VLP vaccine induced strong humoral and CMI responses with antigen-specific activation of CD3(+) T cells. Compared to animals injected with placebo, ferrets vaccinated with alum-adjuvanted vaccine displayed no weight loss during the challenge. Moreover, the vaccination significantly reduced the viral load in lungs and nasal washes 3 days after the infection. This candidate plant-made H7 vaccine therefore induced protective responses after either one adjuvanted or two unadjuvanted doses. Studies are currently ongoing to better characterize the immune response elicited by the plant-derived VLP vaccines. Regardless, these data are very promising for the rapid production of an immunogenic and protective vaccine against

  6. Competitive Fitness of Influenza B Viruses Possessing E119A and H274Y Neuraminidase Inhibitor Resistance–Associated Substitutions in Ferrets

    PubMed Central

    Pascua, Philippe Noriel Q.; Marathe, Bindumadhav M.; Burnham, Andrew J.; Vogel, Peter; Webby, Richard J.; Webster, Robert G.; Govorkova, Elena A.

    2016-01-01

    Neuraminidase (NA) inhibitors (NAIs) are the only antiviral drugs recommended for influenza treatment and prophylaxis. Although NAI-resistant influenza B viruses that could pose a threat to public health have been reported in the field, their fitness is poorly understood. We evaluated in ferrets the pathogenicity and relative fitness of reverse genetics (rg)–generated influenza B/Yamanashi/166/1998-like viruses containing E119A or H274Y NA substitutions (N2 numbering). Ferrets inoculated with NAI-susceptible rg–wild-type (rg-WT) or NAI-resistant (rg-E119A or rg-H274Y) viruses developed mild infections. Growth of rg-E119A virus in the nasal cavities was delayed, but the high titers at 3 days post-inoculation (dpi) were comparable to those of the rg-WT and rg-H274Y viruses (3.6–4.1 log10TCID50/mL). No virus persisted beyond 5 dpi and replication did not extend to the trachea or lungs. Positive virus antigen-staining of the nasal turbinate epithelium was intermittent with the rg-WT and rg-H274Y viruses; whereas antigen-staining for the rg-E119A virus was more diffuse. Virus populations in ferrets coinoculated with NAI-susceptible and -resistant viruses (1:1 mixture) remained heterogeneous at 5 dpi but were predominantly rg-WT (>70%). Although the E119A substitution was associated with delayed replication in ferrets, the H274Y substitution did not measurably affect viral growth properties. These data suggest that rg-H274Y has undiminished fitness in single virus inoculations, but neither rg-E119A nor rg-H274Y gained a fitness advantage over rg-WT in direct competition experiments without antiviral drug pressure. Taken together, our data suggest the following order of relative fitness in a ferret animal model: rg-WT > rg-H274Y > rg-E119A. PMID:27466813

  7. Avian Influenza H7N9/13 and H7N7/13: a Comparative Virulence Study in Chickens, Pigeons, and Ferrets

    PubMed Central

    Kalthoff, Donata; Bogs, Jessica; Grund, Christian; Tauscher, Kerstin; Teifke, Jens P.; Starick, Elke; Harder, Timm

    2014-01-01

    ABSTRACT Human influenza cases caused by a novel avian H7N9 virus in China emphasize the zoonotic potential of that subtype. We compared the infectivity and pathogenicity of the novel H7N9 virus with those of a recent European avian H7N7 strain in chickens, pigeons, and ferrets. Neither virus induced signs of disease despite substantial replication in inoculated chickens and rapid transmission to contact chickens. Evidence of the replication of both viruses in pigeons, albeit at lower levels of RNA excretion, was also detected. No clear-cut differences between the two H7 isolates emerged regarding replication and antibody development in avian hosts. In ferrets, in contrast, greater replication of the avian H7N9 virus than of the H7N7 strain was observed with significant differences in viral presence, e.g., in nasal wash, lung, and cerebellum samples. Importantly, both viruses showed the potential to spread to the mammal brain. We conclude that efficient asymptomatic viral replication and shedding, as shown in chickens, facilitate the spread of H7 viruses that may harbor zoonotic potential. Biosafety measures are required for the handling of poultry infected with avian influenza viruses of the H7 subtype, independently of their pathogenicity for gallinaceous poultry. IMPORTANCE This study is important to the field since it provides data about the behavior of the novel H7N9 avian influenza virus in chickens, pigeons, and ferrets in comparison with that of a recent low-pathogenicity H7N7 strain isolated from poultry. We clearly show that chickens, but not pigeons, are highly permissive hosts of both H7 viruses, allowing high-titer replication and virus shedding without any relevant clinical signs. In the ferret model, the potential of both viruses to infect mammals could be demonstrated, including infection of the brain. However, the replication efficiency of the H7N9 virus in ferrets was higher than that of the H7N7 strain. In conclusion, valuable data for the risk

  8. Randomized Controlled Ferret Study to Assess the Direct Impact of 2008–09 Trivalent Inactivated Influenza Vaccine on A(H1N1)pdm09 Disease Risk

    PubMed Central

    Skowronski, Danuta M.; Hamelin, Marie-Eve; De Serres, Gaston; Janjua, Naveed Z.; Li, Guiyun; Sabaiduc, Suzana; Bouhy, Xavier; Couture, Christian; Leung, Anders; Kobasa, Darwyn; Embury-Hyatt, Carissa; de Bruin, Erwin; Balshaw, Robert; Lavigne, Sophie; Petric, Martin; Koopmans, Marion; Boivin, Guy

    2014-01-01

    During spring-summer 2009, several observational studies from Canada showed increased risk of medically-attended, laboratory-confirmed A(H1N1)pdm09 illness among prior recipients of 2008–09 trivalent inactivated influenza vaccine (TIV). Explanatory hypotheses included direct and indirect vaccine effects. In a randomized placebo-controlled ferret study, we tested whether prior receipt of 2008–09 TIV may have directly influenced A(H1N1)pdm09 illness. Thirty-two ferrets (16/group) received 0.5 mL intra-muscular injections of the Canadian-manufactured, commercially-available, non-adjuvanted, split 2008–09 Fluviral or PBS placebo on days 0 and 28. On day 49 all animals were challenged (Ch0) with A(H1N1)pdm09. Four ferrets per group were randomly selected for sacrifice at day 5 post-challenge (Ch+5) and the rest followed until Ch+14. Sera were tested for antibody to vaccine antigens and A(H1N1)pdm09 by hemagglutination inhibition (HI), microneutralization (MN), nucleoprotein-based ELISA and HA1-based microarray assays. Clinical characteristics and nasal virus titers were recorded pre-challenge then post-challenge until sacrifice when lung virus titers, cytokines and inflammatory scores were determined. Baseline characteristics were similar between the two groups of influenza-naïve animals. Antibody rise to vaccine antigens was evident by ELISA and HA1-based microarray but not by HI or MN assays; virus challenge raised antibody to A(H1N1)pdm09 by all assays in both groups. Beginning at Ch+2, vaccinated animals experienced greater loss of appetite and weight than placebo animals, reaching the greatest between-group difference in weight loss relative to baseline at Ch+5 (7.4% vs. 5.2%; p = 0.01). At Ch+5 vaccinated animals had higher lung virus titers (log-mean 4.96 vs. 4.23pfu/mL, respectively; p = 0.01), lung inflammatory scores (5.8 vs. 2.1, respectively; p = 0.051) and cytokine levels (p>0.05). At Ch+14, both groups had recovered. Findings in

  9. [Sequencing and analysis of complete genome of rabies viruses isolated from Chinese Ferret-Badger and dog in Zhejiang province].

    PubMed

    Lei, Yong-Liang; Wang, Xiao-Guang; Tao, Xiao-Yan; Li, Hao; Meng, Sheng-Li; Chen, Xiu-Ying; Liu, Fu-Ming; Ye, Bi-Feng; Tang, Qing

    2010-01-01

    Based on sequencing the full-length genomes of four Chinese Ferret-Badger and dog, we analyze the properties of rabies viruses genetic variation in molecular level, get the information about rabies viruses prevalence and variation in Zhejiang, and enrich the genome database of rabies viruses street strains isolated from China. Rabies viruses in suckling mice were isolated, overlapped fragments were amplified by RT-PCR and full-length genomes were assembled to analyze the nucleotide and deduced protein similarities and phylogenetic analyses from Chinese Ferret-Badger, dog, sika deer, vole, used vaccine strain were determined. The four full-length genomes were sequenced completely and had the same genetic structure with the length of 11, 923 nts or 11, 925 nts including 58 nts-Leader, 1353 nts-NP, 894 nts-PP, 609 nts-MP, 1575 nts-GP, 6386 nts-LP, and 2, 5, 5 nts- intergenic regions(IGRs), 423 nts-Pseudogene-like sequence (psi), 70 nts-Trailer. The four full-length genomes were in accordance with the properties of Rhabdoviridae Lyssa virus by BLAST and multi-sequence alignment. The nucleotide and amino acid sequences among Chinese strains had the highest similarity, especially among animals of the same species. Of the four full-length genomes, the similarity in amino acid level was dramatically higher than that in nucleotide level, so the nucleotide mutations happened in these four genomes were most synonymous mutations. Compared with the reference rabies viruses, the lengths of the five protein coding regions had no change, no recombination, only with a few point mutations. It was evident that the five proteins appeared to be stable. The variation sites and types of the four genomes were similar to the reference vaccine or street strains. And the four strains were genotype 1 according to the multi-sequence and phylogenetic analyses, which possessed the distinct district characteristics of China. Therefore, these four rabies viruses are likely to be street viruses

  10. Frequency-band signatures of visual responses to naturalistic input in ferret primary visual cortex during free viewing.

    PubMed

    Sellers, Kristin K; Bennett, Davis V; Fröhlich, Flavio

    2015-02-19

    Neuronal firing responses in visual cortex reflect the statistics of visual input and emerge from the interaction with endogenous network dynamics. Artificial visual stimuli presented to animals in which the network dynamics were constrained by anesthetic agents or trained behavioral tasks have provided fundamental understanding of how individual neurons in primary visual cortex respond to input. In contrast, very little is known about the mesoscale network dynamics and their relationship to microscopic spiking activity in the awake animal during free viewing of naturalistic visual input. To address this gap in knowledge, we recorded local field potential (LFP) and multiunit activity (MUA) simultaneously in all layers of primary visual cortex (V1) of awake, freely viewing ferrets presented with naturalistic visual input (nature movie clips). We found that naturalistic visual stimuli modulated the entire oscillation spectrum; low frequency oscillations were mostly suppressed whereas higher frequency oscillations were enhanced. In average across all cortical layers, stimulus-induced change in delta and alpha power negatively correlated with the MUA responses, whereas sensory-evoked increases in gamma power positively correlated with MUA responses. The time-course of the band-limited power in these frequency bands provided evidence for a model in which naturalistic visual input switched V1 between two distinct, endogenously present activity states defined by the power of low (delta, alpha) and high (gamma) frequency oscillatory activity. Therefore, the two mesoscale activity states delineated in this study may define the degree of engagement of the circuit with the processing of sensory input.

  11. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance.

    PubMed

    Frise, Rebecca; Bradley, Konrad; van Doremalen, Neeltje; Galiano, Monica; Elderfield, Ruth A; Stilwell, Peter; Ashcroft, Jonathan W; Fernandez-Alonso, Mirian; Miah, Shahjahan; Lackenby, Angie; Roberts, Kim L; Donnelly, Christl A; Barclay, Wendy S

    2016-07-19

    Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution.

  12. Frequency-Band Signatures of Visual Responses to Naturalistic Input in Ferret Primary Visual Cortex during Free Viewing

    PubMed Central

    Sellers, Kristin K.; Bennett, Davis V.; Frohlich, Flavio

    2015-01-01

    Neuronal firing responses reflect the statistics of visual input and emerge from the interaction with endogenous network dynamics. Artificial visual stimuli presented to animals in which the network dynamics were constrained by anesthetic agents or trained behavioral tasks have provided fundamental understanding of how individual neurons in primary visual cortex respond to input. In contrast, very little is known about the mesoscale network dynamics and their relationship to microscopic spiking activity in the awake animal during free viewing of naturalistic visual input. To address this gap in knowledge, we recorded local field potential (LFP) and multiunit activity (MUA) in all layers of primary visual cortex (V1) of awake, freely viewing ferrets presented with naturalistic visual input (nature movie clips). We found that naturalistic visual stimuli modulated the entire oscillation spectrum; low frequency oscillations were mostly suppressed whereas higher frequency oscillations were enhanced. In average across all cortical layers, stimulus-induced change in delta and alpha power negatively correlated with the MUA responses, whereas sensory-evoked increases in gamma power positively correlated with MUA responses. The time-course of the band-limited power in these frequency bands provided evidence for a model in which naturalistic visual input switched V1 between two distinct, endogenously present activity states defined by the power of low (delta, alpha) and high (gamma) frequency oscillatory activity. Therefore, the two mesoscale activity states delineated in this study may define the engagement of the circuit with processing sensory input at the level of spiking activity. PMID:25498982

  13. Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

    PubMed Central

    Frise, Rebecca; Bradley, Konrad; van Doremalen, Neeltje; Galiano, Monica; Elderfield, Ruth A.; Stilwell, Peter; Ashcroft, Jonathan W.; Fernandez-Alonso, Mirian; Miah, Shahjahan; Lackenby, Angie; Roberts, Kim L.; Donnelly, Christl A.; Barclay, Wendy S.

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution. PMID:27430528

  14. [Effect of the 5-HT3 receptor antagonist granisetron on estramustine phosphate sodium (Estracyt)-induced emesis in ferrets].

    PubMed

    Higashioka, Masaya; Yamaguchi, Emi; Takatori, Shingo; Tanaka, Mitsushi; Kyoi, Takashi

    2010-07-01

    Estracyt(R) is an antimitotic drug used for the treatment of prostate cancer, and its most common adverse effects are nausea and vomiting. In this study, we investigated the effect of a 5-HT3 receptor antagonist, granisetron, on emesis induced in ferrets by estramustine phosphate sodium (EMP), the active ingredient of Estracyt. To clarify the mechanism of action of EMP-induced emesis, we also investigated the effect of EMP on the release of serotonin (5-HT) in the isolated rat ileum. EMP (3 mg/kg, per os) induced 75.3+/-10.2 retching episodes and 7.5+/-1.3 vomiting episodes during a 2-h observation period. The latency to the first emetic response was 58.0+/-13.5 min. Granisetron (0.1 mg/kg, per os) administered 1 h before the administration of EMP reduced the number of EMP-induced retching and vomiting episodes to 1.3+/-1.3 and 1.0+/-1.0, respectively, and prolonged the latency by a factor of almost two. EMP (10-5 and 10-4 M) increased 5-HT release from isolated rat ileum, and 10 -7 M granisetron almost completely inhibited the increase induced by 10-4 M EMP. These results suggest that EMP induces nausea and vomiting via 5-HT release from the ileum, and that 5-HT3 receptor antagonists may be useful to prevent gastrointestinal adverse effects that occur during treatment with Estracyt.

  15. Mechanism of ischemic contracture in ferret hearts: relative roles of [Ca2+]i elevation and ATP depletion.

    PubMed

    Koretsune, Y; Marban, E

    1990-01-01

    When coronary perfusion is interrupted, the diastolic force generated by the myocardium first falls but eventually increases. The delayed rise in force, ischemic contracture, has been attributed either to ATP depletion or to elevation of the intracellular free calcium concentration ([Ca2+]i). To distinguish between these possibilities, we measured [Ca2+]i and ATP concentration [( ATP]) in ferret hearts using nuclear magnetic resonance (NMR) spectroscopy. Mean time-average [Ca2+]i and [ATP] equaled 0.25 microM and 2.7 mumol/g wet wt, respectively, under control perfusion conditions. [Ca2+]i increased and [ATP] fell during total global ischemia. Although [Ca2+]i exceeded the usual systolic levels of 1.7 microM within 20-25 min of ischemia and reached a steady level between 2 and 3 microM by 30-35 min, force only began to rise after 40 min. In contrast, the time required for [ATP] to fall to less than 10% of control levels coincided closely with the onset of contracture. Ischemia in the presence of iodoacetate, an inhibitor of glycolysis, led to a precipitous fall in [ATP] and a concomitant rise in force, both of which preceded any elevation of [Ca2+]i. Thus changes in [Ca2+]i are neither sufficient nor necessary for the initiation of ischemic contracture. We conclude that ATP depletion is primary and that the rise in resting force reflects the formation of rigor cross bridges.

  16. Supplementation of H1N1pdm09 split vaccine with heterologous tandem repeat M2e5x virus-like particles confers improved cross-protection in ferrets.

    PubMed

    Music, Nedzad; Reber, Adrian J; Kim, Min-Chul; York, Ian A; Kang, Sang-Moo

    2016-01-20

    Current influenza vaccines induce strain-specific immunity to the highly variable hemagglutinin (HA) protein. It is therefore a high priority to develop vaccines that induce broadly cross-protective immunity to different strains of influenza. Since influenza A M2 proteins are highly conserved among different strains, five tandem repeats of the extracellular peptide of M2 in a membrane-anchored form on virus-like particles (VLPs) have been suggested to be a promising candidate for universal influenza vaccine. In this study, ferrets were intramuscularly immunized with 2009 H1N1 split HA vaccine ("Split") alone, influenza split vaccine supplemented with M2e5x VLP ("Split+M2e5x"), M2e5x VLP alone ("M2e5x"), or mock immunized. Vaccine efficacy was measured serologically and by protection against a serologically distinct viral challenge. Ferrets immunized with Split+M2e5x induced HA strain specific and conserved M2e immunity. Supplementation of M2e5x VLP to split vaccination significantly increased the immunogenicity of split vaccine compared to split alone. The Split+M2e5x ferret group showed evidence of cross-reactive protection, including faster recovery from weight loss, and reduced inflammation, as inferred from changes in peripheral leukocyte subsets, compared to mock-immunized animals. In addition, ferrets immunized with Split+M2e5x shed lower viral nasal-wash titers than the other groups. Ferrets immunized with M2e5x alone also show some protective effects, while those immunized with split vaccine alone induced no protective effects compared to mock-immunized ferrets. These studies suggest that supplementation of split vaccine with M2e5x-VLP may provide broader and improved cross-protection than split vaccine alone. PMID:26709639

  17. Lower Respiratory Tract Infection of the Ferret by 2009 H1N1 Pandemic Influenza A Virus Triggers Biphasic, Systemic, and Local Recruitment of Neutrophils

    PubMed Central

    Camp, Jeremy V.; Bagci, Ulas; Chu, Yong-Kyu; Squier, Brendan; Fraig, Mostafa; Uriarte, Silvia M.; Guo, Haixun; Mollura, Daniel J.

    2015-01-01

    ABSTRACT Infection of the lower respiratory tract by influenza A viruses results in increases in inflammation and immune cell infiltration in the lung. The dynamic relationships among the lung microenvironments, the lung, and systemic host responses during infection remain poorly understood. Here we used extensive systematic histological analysis coupled with live imaging to gain access to these relationships in ferrets infected with the 2009 H1N1 pandemic influenza A virus (H1N1pdm virus). Neutrophil levels rose in the lungs of H1N1pdm virus-infected ferrets 6 h postinfection and became concentrated at areas of the H1N1pdm virus-infected bronchiolar epithelium by 1 day postinfection (dpi). In addition, neutrophil levels were increased throughout the alveolar spaces during the first 3 dpi and returned to baseline by 6 dpi. Histochemical staining revealed that neutrophil infiltration in the lungs occurred in two waves, at 1 and 3 dpi, and gene expression within microenvironments suggested two types of neutrophils. Specifically, CCL3 levels, but not CXCL8/interleukin 8 (IL-8) levels, were higher within discrete lung microenvironments and coincided with increased infiltration of neutrophils into the lung. We used live imaging of ferrets to monitor host responses within the lung over time with [18F]fluorodeoxyglucose (FDG). Sites in the H1N1pdm virus-infected ferret lung with high FDG uptake had high levels of proliferative epithelium. In summary, neutrophils invaded the H1N1pdm virus-infected ferret lung globally and focally at sites of infection. Increased neutrophil levels in microenvironments did not correlate with increased FDG uptake; hence, FDG uptake may reflect prior infection and inflammation of lungs that have experienced damage, as evidenced by bronchial regeneration of tissues in the lungs at sites with high FDG levels. IMPORTANCE Severe influenza disease is characterized by an acute infection of the lower airways that may progress rapidly to organ failure

  18. The genetic legacy of the 19th-century decline of the British polecat: evidence for extensive introgression from feral ferrets.

    PubMed

    Costa, M; Fernandes, C; Birks, J D S; Kitchener, A C; Santos-Reis, M; Bruford, M W

    2013-10-01

    In the 19th century, the British polecat suffered a demographic contraction, as a consequence of direct persecution, reaching its lowest population in the years that preceded the First World War. The polecat is now recovering and expanding throughout Britain, but introgressive hybridization with feral ferrets has been reported, which could be masking the true range of the polecat and introducing domestic genes into the species. We used a fragment of the mitochondrial DNA control region and 11 microsatellite loci to characterize the frequency and extent of hybridization and introgression between the two species and assess whether the 19th-century decline corresponded to a genetic bottleneck in the polecat. The proportion of admixture detected in the wild was high (31%) and hybrids were more frequently found outside Wales, suggesting that hybridization is more likely to occur along the eastern edge of the polecat's range expansion. The patterns observed in the mitochondrial and nuclear DNA data show that introgression was mediated by crosses between male polecats and female ferrets, whose offspring backcrossed with polecats. No first-generation (F1 ) hybrids were identified, and the broad range of observed admixture proportions agrees with a scenario of past extensive hybridization between the two species. Using several different methods to investigate demographic history, we did not find consistent evidence for a genetic bottleneck in the British polecat, a result that could be interpreted as a consequence of hybridization with ferrets. Our results highlight the importance of the Welsh polecat population for the conservation and restoration of the genetic identity of the British polecat.

  19. Evaluation of vaccines for H5N1 influenza virus in ferrets reveals the potential for protective single-shot immunization.

    PubMed

    Middleton, Deborah; Rockman, Steven; Pearse, Martin; Barr, Ian; Lowther, Sue; Klippel, Jessica; Ryan, David; Brown, Lorena

    2009-08-01

    As part of influenza pandemic preparedness, policy decisions need to be made about how best to utilize vaccines once they are manufactured. Since H5N1 avian influenza virus has the potential to initiate the next human pandemic, isolates of this subtype have been used for the production and testing of prepandemic vaccines. Clinical trials of such vaccines indicate that two injections of preparations containing adjuvant will be required to induce protective immunity. However, this is a working assumption based on classical serological measures only. Examined here are the dose of viral hemagglutinin (HA) and the number of inoculations required for two different H5N1 vaccines to achieve protection in ferrets after lethal H5N1 challenge. Ferrets inoculated twice with 30 microg of A/Vietnam/1194/2004 HA vaccine with AlPO4, or with doses as low as 3.8 microg of HA with Iscomatrix (ISCOMATRIX, referred to as Iscomatrix herein, is a registered trademark of CSL Limited) adjuvant, were completely protected against death and disease after H5N1 challenge, and the protection lasted at least 15 months. Cross-clade protection was also observed with both vaccines. Significantly, complete protection against death could be achieved with only a single inoculation of H5N1 vaccine containing as little as 15 microg of HA with AlPO4 or 3.8 microg of HA with Iscomatrix adjuvant. Ferrets vaccinated with the single-injection Iscomatrix vaccines showed fewer clinical manifestations of infection than those given AlPO4 vaccines and remained highly active. Our data provide the first indication that in the event of a future influenza pandemic, effective mass vaccination may be achievable with a low-dose "single-shot" vaccine and provide not only increased survival but also significant reduction in disease severity.

  20. Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets

    PubMed Central

    Rosendahl Huber, S. K.; Camps, M. G. M.; Jacobi, R. H. J.; Mouthaan, J.; van Dijken, H.; van Beek, J.; Ossendorp, F.; de Jonge, J.

    2015-01-01

    Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks. PMID:26046664

  1. Differential cortical laminar structure revealed by NeuN immunostaining and myeloarchitecture between sulcal and gyral regions independent of sexual dimorphisms in the ferret cerebrum.

    PubMed

    Horiuchi-Hirose, Miwa; Sawada, Kazuhiko

    2016-08-01

    The purpose of this study was to quantitatively clarify differences in laminar structure and myeloarchitecture of sulcal and gyral regions of the cerebral cortex of ferrets. Histological sections of cerebrum from male and female ferrets at postnatal day 90 were made at the coronal plane, and were immunostained with anti-NeuN or anti-myelin basic protein (MBP). Thickness was estimated in the entire depth or three strata, that is, layer I, outer (layers II-III) and inner (layers IV-VI) strata of the neocortex in representative five sulcal and seven gyral regions. As with the entire cortical depth, outer and inner strata were significantly thinner in the sulcal bottoms than in the gyral crowns, whereas layer I had about twofold greater thickness in the sulcal bottoms. However, thicknesses of the entire cortical depth and each cortical stratum were not statistically different among five sulcal regions or seven gyral regions examined. By MBP immunostaining, myelin fibers ran tangentially through the superficial regions of layer I in gyral crowns. Those fibers were relatively denser in gyri of frontal and temporal regions, and relatively sparse in gyri of parietal and occipital regions, although their density in any gyri was not different between sexes. These results show a differential laminar structure and myeloarchitecture between the sulcal and gyral regions of the ferret cerebral cortex present in both sexes. Myelination of layer I tangential fibers varied among primary gyri and was weaker in phylogenetically higher-order cortical gyri. Anat Rec, 299:1003-1011, 2016. © 2016 Wiley Periodicals, Inc.

  2. A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets, and monkeys.

    PubMed

    Min, Ji-Young; Vogel, Leatrice; Matsuoka, Yumiko; Lu, Bin; Swayne, David; Jin, Hong; Kemble, George; Subbarao, Kanta

    2010-11-01

    A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of highly pathogenic (HP) A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (H2N2) virus. The reassortant H7N7 NL/03 ca vaccine virus was temperature sensitive and attenuated in mice, ferrets, and African green monkeys (AGMs). Intranasal (i.n.) administration of a single dose of the H7N7 NL/03 ca vaccine virus fully protected mice from lethal challenge with homologous and heterologous H7 viruses from Eurasian and North American lineages. Two doses of the H7N7 NL/03 ca vaccine induced neutralizing antibodies in serum and provided complete protection from pulmonary replication of homologous and heterologous wild-type H7 challenge viruses in mice and ferrets. One dose of the H7N7 NL/03 ca vaccine elicited an antibody response in one of three AGMs that was completely protected from pulmonary replication of the homologous wild-type H7 challenge virus. The contribution of CD8(+) and/or CD4(+) T cells to the vaccine-induced protection of mice was evaluated by T-cell depletion; T lymphocytes were not essential for the vaccine-induced protection from lethal challenge with H7 wt viruses. Additionally, passively transferred neutralizing antibody induced by the H7N7 NL/03 ca virus protected mice from lethality following challenge with H7 wt viruses. The safety, immunogenicity, and efficacy of the H7N7 NL/03 ca vaccine virus in mice, ferrets, and AGMs support the evaluation of this vaccine virus in phase I clinical trials. PMID:20810733

  3. Intranasal vaccination with a plant-derived H5 HA vaccine protects mice and ferrets against highly pathogenic avian influenza virus challenge.

    PubMed

    Major, Diane; Chichester, Jessica A; Pathirana, Rishi D; Guilfoyle, Kate; Shoji, Yoko; Guzman, Carlos A; Yusibov, Vidadi; Cox, Rebecca J

    2015-01-01

    Highly pathogenic avian influenza H5N1 infection remains a public health threat and vaccination is the best measure of limiting the impact of a potential pandemic. Mucosal vaccines have the advantage of eliciting immune responses at the site of viral entry, thereby preventing infection as well as further viral transmission. In this study, we assessed the protective efficacy of hemagglutinin (HA) from the A/Indonesia/05/05 (H5N1) strain of influenza virus that was produced by transient expression in plants. The plant-derived vaccine, in combination with the mucosal adjuvant (3',5')-cyclic dimeric guanylic acid (c-di-GMP) was used for intranasal immunization of mice and ferrets, before challenge with a lethal dose of the A/Indonesia/05/05 (H5N1) virus. Mice vaccinated with 15 μg or 5 μg of adjuvanted HA survived the viral challenge, while all control mice died within 10 d of challenge. Vaccinated animals elicited serum hemagglutination inhibition, IgG and IgA antibody titers. In the ferret challenge study, all animals vaccinated with the adjuvanted plant vaccine survived the lethal viral challenge, while 50% of the control animals died. In both the mouse and ferret models, the vaccinated animals were better protected from weight loss and body temperature changes associated with H5N1 infection compared with the non-vaccinated controls. Furthermore, the systemic spread of the virus was lower in the vaccinated animals compared with the controls. Results presented here suggest that the plant-produced HA-based influenza vaccine adjuvanted with c-di-GMP is a promising vaccine/adjuvant combination for the development of new mucosal influenza vaccines. PMID:25714901

  4. Virus growth and antibody responses following respiratory tract infection of ferrets and mice with WT and P/V mutants of the paramyxovirus Simian Virus 5

    PubMed Central

    Capraro, Gerald A.; Johnson, John B.; Kock, Nancy D.; Parks, Griffith D.

    2008-01-01

    P/V gene substitutions convert the non-cytopathic paramyxovirus Simian Virus 5 (SV5), which is a poor inducer of host cell responses in human tissue culture cells, into a mutant (P/V-CPI–) that induces high levels of apoptosis, interferon (IFN)-beta, and proinflammatory cytokines. However, the effect of SV5-P/V gene mutations on virus growth and adaptive immune responses in animals has not been determined. Here, we used two distinct animal model systems to test the hypothesis that SV5-P/V mutants which are more potent activators of innate responses in tissue culture will also elicit higher antiviral antibody responses. In mouse cells, in vitro studies identified a panel of SV5-P/V mutants that ranged in their ability to limit IFN responses. Intranasal infection of mice with these WT and P/V mutant viruses elicited equivalent anti-SV5 IgG responses at all doses tested, and viral titers recovered from the respiratory tract were indistinguishable. In primary cultures of ferret lung fibroblasts, WT rSV5 and P/V-CPI– viruses had phenotypes similar to those established in human cell lines, including differential induction of IFN secretion, IFN signaling and apoptosis. Intranasal infection of ferrets with a low dose of WT rSV5 elicited ~500 fold higher anti-SV5 serum IgG responses compared to the P/V-CPI– mutant, and this correlated with overall higher viral titers for the WT virus in tracheal tissues. There was a dose-dependent increase in antibody response to infection of ferrets with P/V-CPI–, but not with WT rSV5. Together our data indicate that WT rSV5 and P/V mutants can elicit distinct innate and adaptive immunity phenotypes in the ferret animal model system, but not in the mouse system. We present a model for the effect of P/V gene substitutions on SV5 growth and immune responses in vivo. PMID:18456301

  5. Increased Acid Stability of the Hemagglutinin Protein Enhances H5N1 Influenza Virus Growth in the Upper Respiratory Tract but Is Insufficient for Transmission in Ferrets

    PubMed Central

    Zaraket, Hassan; Bridges, Olga A.; Duan, Susu; Baranovich, Tatiana; Yoon, Sun-Woo; Reed, Mark L.; Salomon, Rachelle; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    Influenza virus entry is mediated by the acidic-pH-induced activation of hemagglutinin (HA) protein. Here, we investigated how a decrease in the HA activation pH (an increase in acid stability) influences the properties of highly pathogenic H5N1 influenza virus in mammalian hosts. We generated isogenic A/Vietnam/1203/2004 (H5N1) (VN1203) viruses containing either wild-type HA protein (activation pH 6.0) or an HA2-K58I point mutation (K to I at position 58) (activation pH 5.5). The VN1203-HA2-K58I virus had replication kinetics similar to those of wild-type VN1203 in MDCK and normal human bronchial epithelial cells and yet had reduced growth in human alveolar A549 cells, which were found to have a higher endosomal pH than MDCK cells. Wild-type and HA2-K58I viruses promoted similar levels of morbidity and mortality in C57BL/6J mice and ferrets, and neither virus transmitted efficiently to naive contact cage-mate ferrets. The acid-stabilizing HA2-K58I mutation, which diminishes H5N1 replication and transmission in ducks, increased the virus load in the ferret nasal cavity early during infection while simultaneously reducing the virus load in the lungs. Overall, a single, acid-stabilizing mutation was found to enhance the growth of an H5N1 influenza virus in the mammalian upper respiratory tract, and yet it was insufficient to enable contact transmission in ferrets in the absence of additional mutations that confer α(2,6) receptor binding specificity and remove a critical N-linked glycosylation site. The information provided here on the contribution of HA acid stability to H5N1 influenza virus fitness and transmissibility in mammals in the background of a non-laboratory-adapted virus provides essential information for the surveillance and assessment of the pandemic potential of currently circulating H5N1 viruses. PMID:23824818

  6. Characterization of the Localized Immune Response in the Respiratory Tract of Ferrets following Infection with Influenza A and B Viruses

    PubMed Central

    Carolan, Louise A.; Rockman, Steve; Borg, Kathryn; Guarnaccia, Teagan; Reading, Patrick; Mosse, Jennifer; Kelso, Anne; Barr, Ian

    2015-01-01

    ABSTRACT The burden of infection with seasonal influenza viruses is significant. Each year is typically characterized by the dominance of one (sub)type or lineage of influenza A or B virus, respectively. The incidence of disease varies annually, and while this may be attributed to a particular virus strain or subtype, the impacts of prior immunity, population differences, and variations in clinical assessment are also important. To improve our understanding of the impacts of seasonal influenza viruses, we directly compared clinical symptoms, virus shedding, and expression of cytokines, chemokines, and immune mediators in the upper respiratory tract (URT) of ferrets infected with contemporary A(H1N1)pdm09, A(H3N2), or influenza B virus. Gene expression in the lower respiratory tract (LRT) was also assessed. Clinical symptoms were minimal. Overall cytokine/chemokine profiles in the URT were consistent in pattern and magnitude between animals infected with influenza A and B viruses, and peak expression levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p40, alpha interferon (IFN-α), IFN-β, and tumor necrosis factor alpha (TNF-α) mRNAs correlated with peak levels of viral shedding. MCP1 and IFN-γ were expressed after the virus peak. Granzymes A and B and IL-10 reached peak expression as the virus was cleared and seroconversion was detected. Cytokine/chemokine gene expression in the LRT following A(H1N1)pdm09 virus infection reflected the observations seen for the URT but was delayed 2 or 3 days, as was virus replication. These data indicate that disease severities and localized immune responses following infection with seasonal influenza A and B viruses are similar, suggesting that other factors are likely to modulate the incidence and impact of seasonal influenza. IMPORTANCE Both influenza A and B viruses cocirculate in the human population, and annual influenza seasons are typically dominated by an influenza A virus subtype or an influenza B virus lineage

  7. Permeability of ferret trachea in vitro to {sup 99m}{Tc}-DTPA and [{sup 14}C]antipyrine

    SciTech Connect

    Hanafi, Z.; Webber, S.E.; Widdicombe, J.G.

    1994-09-01

    Platelet-activating factor (PAF) and vasoactive drugs were tested on permeability of ferret trachea in vitro by measuring fluxes of {sup 99m}{Tc}-diethylenetriamine pentaacetic acid ({sup 99m}{Tc}-DTPA; hydrophilic) and [{sup 14}C]antipyrine ([{sup 14}C]AP; lipophilic) across the tracheal wall. Tracheae were bathed on both sides with Krebs-Henseleit buffer, with luminal buffer containing either {sup 99m}{Tc}-DTPA or [{sup 14}C]AP. Luminal and abluminal radioactivities, potential difference, and tracheal smooth muscle tone were measured. Baseline {sup 99m}{Tc}-DTPA and [{sup 14}C]AP permeability coefficients were - 4.7 {+-} 0.6 (SE) x 10{sup {minus}7} and -2.2 {+-} 0.1 x 10{sup {minus}5} cm/s, respectively. PAF (10 {mu}M) increased permeability to {sup 99m}{Tc}-DTPA to -35.3 {+-} 7.6 x 10{sup {minus}7} cm/s (P < 0.05), but permeability to [{sup 14}C]AP did not change, suggesting that paracellular but not transcellular transport was affected. Abluminal and luminal applications of methacholine (MCh, 20 {mu}M), phenylephrine (PE, 100 {mu}M), and albuterol (Alb, 100 {mu}M) caused no change in permeability to {sup 99m}{Tc}-DTPA before or after exposure to luminal PAF, but abluminal histamine (Hist, 10 {mu}M) significantly increased permeability. Abluminal Hist decreased permeability to [{sup 14}C]AP before and after exposure to PAF. MCh, PE, and Hist increased smooth muscle tone; Alb and PAF had no effect. Thus, only PAF and Hist altered permeability to {sup 99m}{Tc}-DTPA, and MCh, PE, and Hist changed smooth muscle tone. Tracheal permeability changes were greater for the hydrophilic than for the lipophilic agent. 37 refs., 11 figs., 1 tab.

  8. Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses

    PubMed Central

    Yang, Huanliang; Chen, Yan; Qiao, Chuanling; He, Xijun; Zhou, Hong; Sun, Yu; Yin, Hang; Meng, Shasha; Liu, Liping; Zhang, Qianyi; Kong, Huihui; Gu, Chunyang; Li, Chengjun; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2016-01-01

    Pigs are important intermediate hosts for generating novel influenza viruses. The Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses (SIVs) have circulated in pigs since 1979, and human cases associated with EAH1N1 SIVs have been reported in several countries. However, the biologic properties of EAH1N1 SIVs are largely unknown. Here, we performed extensive influenza surveillance in pigs in China and isolated 228 influenza viruses from 36,417 pigs. We found that 139 of the 228 strains from pigs in 10 provinces in China belong to the EAH1N1 lineage. These viruses formed five genotypes, with two distinct antigenic groups, represented by A/swine/Guangxi/18/2011 and A/swine/Guangdong/104/2013, both of which are antigenically and genetically distinct from the current human H1N1 viruses. Importantly, the EAH1N1 SIVs preferentially bound to human-type receptors, and 9 of the 10 tested viruses transmitted in ferrets by respiratory droplet. We found that 3.6% of children (≤10 y old), 0% of adults, and 13.4% of elderly adults (≥60 y old) had neutralization antibodies (titers ≥40 in children and ≥80 in adults) against the EAH1N1 A/swine/Guangxi/18/2011 virus, but none of them had such neutralization antibodies against the EAH1N1 A/swine/Guangdong/104/2013 virus. Our study shows the potential of EAH1N1 SIVs to transmit efficiently in humans and suggests that immediate action is needed to prevent the efficient transmission of EAH1N1 SIVs to humans. PMID:26711995

  9. The claustrum of the ferret: afferent and efferent connections to lower and higher order visual cortical areas

    PubMed Central

    Patzke, Nina; Innocenti, Giorgio M.; Manger, Paul R.

    2014-01-01

    The claustrum, a subcortical telencephalic structure, is known to be reciprocally interconnected to almost all cortical regions; however, a systematic analysis of claustrocortical connectivity with physiologically identified lower and higher order visual cortical areas has not been undertaken. In the current study we used biotinylated dextran amine to trace the connections of the ferret claustrum with lower (occipital areas 17, 18, 19 and 21) and higher (parietal and temporal areas posterior parietal caudal visual area (PPc), posterior parietal rostral visual area (PPr), 20a, 20b, anterior ectosylvian visual area (AEV)) order visual cortical areas. No connections between the claustrum and area 17 were observed. Occipital visual areas 18, 19 and 21 revealed a reciprocal connectivity mainly to the caudal part of the claustrum. After injection into parietal areas PPc and PPr labeled neurons and terminals were found throughout almost the entire rostrocaudal extent of the dorsal claustrum. Area 20b revealed reciprocal connections mainly to the caudal-ventral claustrum, although some labeled neurons and terminals were observed in the dorso-central claustrum. No projection from the claustrum to areas AEV and 20a could be observed, though projections from AEV and 20a to the claustrum were found. Only injections placed in areas PPr and AEV resulted in anterogradely labeled terminals in the contralateral claustrum. Our results suggest that lower order visual areas have clearly defined connectivity zones located in the caudal claustrum, whereas higher order visual areas, even if not sending and/or receiving projections from the entire claustrum, show a more widespread connectivity. PMID:24616671

  10. Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses.

    PubMed

    Yang, Huanliang; Chen, Yan; Qiao, Chuanling; He, Xijun; Zhou, Hong; Sun, Yu; Yin, Hang; Meng, Shasha; Liu, Liping; Zhang, Qianyi; Kong, Huihui; Gu, Chunyang; Li, Chengjun; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2016-01-12

    Pigs are important intermediate hosts for generating novel influenza viruses. The Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses (SIVs) have circulated in pigs since 1979, and human cases associated with EAH1N1 SIVs have been reported in several countries. However, the biologic properties of EAH1N1 SIVs are largely unknown. Here, we performed extensive influenza surveillance in pigs in China and isolated 228 influenza viruses from 36,417 pigs. We found that 139 of the 228 strains from pigs in 10 provinces in China belong to the EAH1N1 lineage. These viruses formed five genotypes, with two distinct antigenic groups, represented by A/swine/Guangxi/18/2011 and A/swine/Guangdong/104/2013, both of which are antigenically and genetically distinct from the current human H1N1 viruses. Importantly, the EAH1N1 SIVs preferentially bound to human-type receptors, and 9 of the 10 tested viruses transmitted in ferrets by respiratory droplet. We found that 3.6% of children (≤10 y old), 0% of adults, and 13.4% of elderly adults (≥60 y old) had neutralization antibodies (titers ≥40 in children and ≥80 in adults) against the EAH1N1 A/swine/Guangxi/18/2011 virus, but none of them had such neutralization antibodies against the EAH1N1 A/swine/Guangdong/104/2013 virus. Our study shows the potential of EAH1N1 SIVs to transmit efficiently in humans and suggests that immediate action is needed to prevent the efficient transmission of EAH1N1 SIVs to humans.

  11. Prevalence, genetics, and transmissibility in ferrets of Eurasian avian-like H1N1 swine influenza viruses.

    PubMed

    Yang, Huanliang; Chen, Yan; Qiao, Chuanling; He, Xijun; Zhou, Hong; Sun, Yu; Yin, Hang; Meng, Shasha; Liu, Liping; Zhang, Qianyi; Kong, Huihui; Gu, Chunyang; Li, Chengjun; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2016-01-12

    Pigs are important intermediate hosts for generating novel influenza viruses. The Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses (SIVs) have circulated in pigs since 1979, and human cases associated with EAH1N1 SIVs have been reported in several countries. However, the biologic properties of EAH1N1 SIVs are largely unknown. Here, we performed extensive influenza surveillance in pigs in China and isolated 228 influenza viruses from 36,417 pigs. We found that 139 of the 228 strains from pigs in 10 provinces in China belong to the EAH1N1 lineage. These viruses formed five genotypes, with two distinct antigenic groups, represented by A/swine/Guangxi/18/2011 and A/swine/Guangdong/104/2013, both of which are antigenically and genetically distinct from the current human H1N1 viruses. Importantly, the EAH1N1 SIVs preferentially bound to human-type receptors, and 9 of the 10 tested viruses transmitted in ferrets by respiratory droplet. We found that 3.6% of children (≤10 y old), 0% of adults, and 13.4% of elderly adults (≥60 y old) had neutralization antibodies (titers ≥40 in children and ≥80 in adults) against the EAH1N1 A/swine/Guangxi/18/2011 virus, but none of them had such neutralization antibodies against the EAH1N1 A/swine/Guangdong/104/2013 virus. Our study shows the potential of EAH1N1 SIVs to transmit efficiently in humans and suggests that immediate action is needed to prevent the efficient transmission of EAH1N1 SIVs to humans. PMID:26711995

  12. H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps.

    PubMed

    Xie, Hang; Wan, Xiu-Feng; Ye, Zhiping; Plant, Ewan P; Zhao, Yangqing; Xu, Yifei; Li, Xing; Finch, Courtney; Zhao, Nan; Kawano, Toshiaki; Zoueva, Olga; Chiang, Meng-Jung; Jing, Xianghong; Lin, Zhengshi; Zhang, Anding; Zhu, Yanhong

    2015-01-01

    The poor performance of 2014-15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009-10, 2010-11 and 2014-15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014-15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014-15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model.

  13. H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps

    NASA Astrophysics Data System (ADS)

    Xie, Hang; Wan, Xiu-Feng; Ye, Zhiping; Plant, Ewan P.; Zhao, Yangqing; Xu, Yifei; Li, Xing; Finch, Courtney; Zhao, Nan; Kawano, Toshiaki; Zoueva, Olga; Chiang, Meng-Jung; Jing, Xianghong; Lin, Zhengshi; Zhang, Anding; Zhu, Yanhong

    2015-10-01

    The poor performance of 2014-15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009-10, 2010-11 and 2014-15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014-15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014-15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model.

  14. H3N2 Mismatch of 2014–15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps

    PubMed Central

    Xie, Hang; Wan, Xiu-Feng; Ye, Zhiping; Plant, Ewan P.; Zhao, Yangqing; Xu, Yifei; Li, Xing; Finch, Courtney; Zhao, Nan; Kawano, Toshiaki; Zoueva, Olga; Chiang, Meng-Jung; Jing, Xianghong; Lin, Zhengshi; Zhang, Anding; Zhu, Yanhong

    2015-01-01

    The poor performance of 2014–15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009–10, 2010–11 and 2014–15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014–15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014–15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model. PMID:26472175

  15. H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps.

    PubMed

    Xie, Hang; Wan, Xiu-Feng; Ye, Zhiping; Plant, Ewan P; Zhao, Yangqing; Xu, Yifei; Li, Xing; Finch, Courtney; Zhao, Nan; Kawano, Toshiaki; Zoueva, Olga; Chiang, Meng-Jung; Jing, Xianghong; Lin, Zhengshi; Zhang, Anding; Zhu, Yanhong

    2015-01-01

    The poor performance of 2014-15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009-10, 2010-11 and 2014-15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014-15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014-15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model. PMID:26472175

  16. Comparison of a human portable glucometer and an automated chemistry analyzer for measurement of blood glucose concentration in pet ferrets (Mustela putorius furo).

    PubMed

    Summa, Noémie M; Eshar, David; Lee-Chow, Bridget; Larrat, Sylvain; Brown, Dorothy C

    2014-09-01

    This study compared blood glucose concentrations measured with a portable blood glucometer and a validated laboratory analyzer in venous blood samples of 20 pet ferrets (Mustela putorius furo). Correlation and agreement were evaluated with a Bland-Altman plot method and Lin's concordance correlation coefficient. Blood glucose concentrations measured with the laboratory analyzer and the glucometer ranged from 1.9 to 8.6 mmol/L and from 0.9 to 9.2 mmol/L, respectively. The glucometer had a poor agreement and correlation with the laboratory analyzer (bias, -0.13 mmol/L; level of agreement, -2.0 to 3.6 mmol/L, concordance correlation coefficient 0.665). The relative sensitivity and specificity of the portable blood glucometer for detection of hypoglycemia were 100% (95% CI: 66% to 100%) and 50% (95% CI: 20% to 80%), respectively. Positive and negative predictive values were 67% (95% CI: 39% to 87%) and 100% (95% CI: 46% to 100%), respectively. Based on these results, clinicians are advised to be cautious when considering the results from this handheld glucometer in pet ferrets, and blood glucose concentrations should be determined with a laboratory analyzer validated for this species.

  17. Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret

    PubMed Central

    Rao, Srinivas S.; Kong, Wing-Pui; Wei, Chih-Jen; Van Hoeven, Neal; Gorres, J. Patrick; Nason, Martha; Andersen, Hanne; Tumpey, Terrence M.; Nabel, Gary J.

    2010-01-01

    Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge. PMID:20352112

  18. The calcium-independent transient outward potassium current in isolated ferret right ventricular myocytes. I. Basic characterization and kinetic analysis

    PubMed Central

    1993-01-01

    Enzymatically isolated myocytes from ferret right ventricles (12-16 wk, male) were studied using the whole cell patch clamp technique. The macroscopic properties of a transient outward K+ current I(to) were quantified. I(to) is selective for K+, with a PNa/PK of 0.082. Activation of I(to) is a voltage-dependent process, with both activation and inactivation being independent of Na+ or Ca2+ influx. Steady-state inactivation is well described by a single Boltzmann relationship (V1/2 = -13.5 mV; k = 5.6 mV). Substantial inactivation can occur during a subthreshold depolarization without any measurable macroscopic current. Both development of and recovery from inactivation are well described by single exponential processes. Ensemble averages of single I(to) channel currents recorded in cell-attached patches reproduce macroscopic I(to) and indicate that inactivation is complete at depolarized potentials. The overall inactivation/recovery time constant curve has a bell-shaped potential dependence that peaks between -10 and -20 mV, with time constants (22 degrees C) ranging from 23 ms (-90 mV) to 304 ms (-10 mV). Steady-state activation displays a sigmoidal dependence on membrane potential, with a net aggregate half- activation potential of +22.5 mV. Activation kinetics (0 to +70 mV, 22 degrees C) are rapid, with I(to) peaking in approximately 5-15 ms at +50 mV. Experiments conducted at reduced temperatures (12 degrees C) demonstrate that activation occurs with a time delay. A nonlinear least- squares analysis indicates that three closed kinetic states are necessary and sufficient to model activation. Derived time constants of activation (22 degrees C) ranged from 10 ms (+10 mV) to 2 ms (+70 mV). Within the framework of Hodgkin-Huxley formalism, Ito gating can be described using an a3i formulation. PMID:8505627

  19. Estimation of systolic and diastolic free intracellular Ca2+ by titration of Ca2+ buffering in the ferret heart.

    PubMed

    Kirschenlohr, H L; Grace, A A; Vandenberg, J I; Metcalfe, J C; Smith, G A

    2000-03-01

    Spectroscopic Ca(2+)-indicators are thought to report values of free intracellular Ca(2+) concentration ([Ca(2+)](i)) that may differ from unperturbed values because they add to the buffering capacity of the tissue. To check this for the heart we have synthesized a new (19)F-labelled NMR Ca(2+) indicator, 1, 2-bis-[2-bis(carboxymethyl)amino-4,5-difluorophenoxy]ethane ('4, 5FBAPTA'), with a low affinity (K(d) 2950 nM). The new indicator and four previously described (19)F-NMR Ca(2+) indicators 1,2-bis-[2-(1 - carboxyethyl)(carboxymethyl)amino - 5 - fluorophenoxy]ethane ('DiMe-5FBAPTA'), 1, 2-bis-[2-(1-carboxyethyl)(carboxymethyl)amino-4-fluorophenoxy]ethane ('DiMe-4FBAPTA'), 1, 2-bis-[2-bis(carboxymethyl)amino-5-fluorophenoxy]ethane ('5FBAPTA') and 1, 2-bis-[2-bis(carboxymethyl)amino-5-fluoro-4-methylphenoxy]ethane ('MFBAPTA'), with dissociation constants for Ca(2+) ranging from 46 to 537 nM, have been used to measure [Ca(2+)](i), over the range from less than 100 nM to more than 3 microM, in Langendorff-perfused ferret hearts (30 degrees C, pH 7.4, paced at 1.0 Hz) by (19)F-NMR spectroscopy. Loading hearts with indicators resulted in buffering of the Ca(2+) transient. The measured end-diastolic and peak-systolic [Ca(2+)](i) were both positively correlated with indicator K(d). The positive correlations between indicator K(d) and the measured end-diastolic and peak-systolic [Ca(2+)](i) were used to estimate the unperturbed end-diastolic and peak-systolic [Ca(2+)](i) by extrapolation to K(d)=0 (diastolic) and to K(d)=infinity (systolic) respectively. The extrapolated values in the intact beating heart were 161 nM for end-diastolic [Ca(2+)](i) and 2650 nM for peak-systolic [Ca(2+)](i), which agree well with values determined from single cells and muscle strips.

  20. Estimation of systolic and diastolic free intracellular Ca2+ by titration of Ca2+ buffering in the ferret heart.

    PubMed Central

    Kirschenlohr, H L; Grace, A A; Vandenberg, J I; Metcalfe, J C; Smith, G A

    2000-01-01

    Spectroscopic Ca(2+)-indicators are thought to report values of free intracellular Ca(2+) concentration ([Ca(2+)](i)) that may differ from unperturbed values because they add to the buffering capacity of the tissue. To check this for the heart we have synthesized a new (19)F-labelled NMR Ca(2+) indicator, 1, 2-bis-[2-bis(carboxymethyl)amino-4,5-difluorophenoxy]ethane ('4, 5FBAPTA'), with a low affinity (K(d) 2950 nM). The new indicator and four previously described (19)F-NMR Ca(2+) indicators 1,2-bis-[2-(1 - carboxyethyl)(carboxymethyl)amino - 5 - fluorophenoxy]ethane ('DiMe-5FBAPTA'), 1, 2-bis-[2-(1-carboxyethyl)(carboxymethyl)amino-4-fluorophenoxy]ethane ('DiMe-4FBAPTA'), 1, 2-bis-[2-bis(carboxymethyl)amino-5-fluorophenoxy]ethane ('5FBAPTA') and 1, 2-bis-[2-bis(carboxymethyl)amino-5-fluoro-4-methylphenoxy]ethane ('MFBAPTA'), with dissociation constants for Ca(2+) ranging from 46 to 537 nM, have been used to measure [Ca(2+)](i), over the range from less than 100 nM to more than 3 microM, in Langendorff-perfused ferret hearts (30 degrees C, pH 7.4, paced at 1.0 Hz) by (19)F-NMR spectroscopy. Loading hearts with indicators resulted in buffering of the Ca(2+) transient. The measured end-diastolic and peak-systolic [Ca(2+)](i) were both positively correlated with indicator K(d). The positive correlations between indicator K(d) and the measured end-diastolic and peak-systolic [Ca(2+)](i) were used to estimate the unperturbed end-diastolic and peak-systolic [Ca(2+)](i) by extrapolation to K(d)=0 (diastolic) and to K(d)=infinity (systolic) respectively. The extrapolated values in the intact beating heart were 161 nM for end-diastolic [Ca(2+)](i) and 2650 nM for peak-systolic [Ca(2+)](i), which agree well with values determined from single cells and muscle strips. PMID:10677357

  1. Benthic foraminiferal thanatocoenoses from the Cap-Ferret Canyon area (NE Atlantic): A complex interplay between hydro-sedimentary and biological processes

    NASA Astrophysics Data System (ADS)

    Duros, P.; Jorissen, F. J.; Cesbron, F.; Zaragosi, S.; Schmidt, S.; Metzger, E.; Fontanier, C.

    2014-06-01

    Benthic foraminiferal thanatocoenoses from the Cap-Ferret Canyon area were studied in the >150-μm fraction of 4-5 cm deep sediment levels, at 13 stations. The shallowest station (151 m depth) is located at the shelf break, close to the canyon head. All other stations are located along two bathymetric transects: seven stations along the canyon axis between 300 and 3000 m depth, and five stations from 300 m to 2000 m depth along the southern flank of the canyon. The comparison between the live (Rose-Bengal-stained) and dead assemblages shows that biological (i.e. population dynamic) and taphonomic processes (i.e. test destruction, transport) generate important discrepancies between live and dead assemblages. An important question is, to what degree post-mortem transport and redeposition of foraminiferal tests contribute to the difference between living and dead assemblages? The composition of the thanatocoenoses (<1% of neritic species) indicates that there is no substantial transport of shells >150 μm from the inner continental shelf to the Cap-Ferret Canyon axis. However, transport of tests from outer shelf or upper canyon axis towards deeper sites occurs, as indicated by an increase of diversity indices of the dead fauna along the canyon axis. Moreover, some species (e.g., Cassidulina carinata) are observed in the living fauna restricted to the shallow sites, but occur in important amounts in the dead fauna at deeper stations, suggesting that these taxa have been transported from upper canyon stations toward deeper sites. Since Cap-Ferret Canyon is inactive in terms of massive sediment transport (i.e. gravity events), downslope transport of foraminiferal tests probably takes place in nepheloid layers. Downslope transports of foraminiferal tests may create important biases for the utilisation of paleoceanographic proxies using the assemblage characteristics and/or the geochemical composition of selected species. However, the study of dead assemblages along a

  2. Impact of prior seasonal H3N2 influenza vaccination or infection on protection and transmission of emerging variants of influenza A(H3N2)v virus in ferrets.

    PubMed

    Houser, Katherine V; Pearce, Melissa B; Katz, Jacqueline M; Tumpey, Terrence M

    2013-12-01

    Influenza H3N2 A viruses continue to circulate in swine and occasionally infect humans, resulting in outbreaks of variant influenza H3N2 [A(H3N2)v] virus. It has been previously demonstrated in ferrets that A(H3N2)v viruses transmit as efficiently as seasonal influenza viruses, raising concern over the pandemic potential of these viruses. However, A(H3N2)v viruses have not acquired the ability to transmit efficiently among humans, which may be due in part to existing cross-reactive immunity to A(H3N2)v viruses. Although current seasonal H3N2 and A(H3N2)v viruses are antigenically distinct from one another, historical H3N2 viruses have some antigenic similarity to A(H3N2)v viruses and previous exposure to these viruses may provide a measure of immune protection sufficient to dampen A(H3N2)v virus transmission. Here, we evaluated whether prior seasonal H3N2 influenza virus vaccination or infection affects virus replication and transmission of A(H3N2)v virus in the ferret animal model. We found that the seasonal trivalent inactivated influenza virus vaccine (TIV) or a monovalent vaccine prepared from an antigenically related 1992 seasonal influenza H3N2 (A/Beijing/32/1992) virus failed to substantially reduce A(H3N2)v (A/Indiana/08/2011) virus shedding and subsequent transmission to naive hosts. Conversely, ferrets primed by seasonal H3N2 virus infection displayed reduced A(H3N2)v virus shedding following challenge, which blunted transmission to naive ferrets. A higher level of specific IgG and IgA antibody titers detected among infected versus vaccinated ferrets was associated with the degree of protection offered by seasonal H3N2 virus infection. The data demonstrate in ferrets that the efficiency of A(H3N2)v transmission is disrupted by preexisting immunity induced by seasonal H3N2 virus infection.

  3. Comparative analyses of pandemic H1N1 and seasonal H1N1, H3N2, and influenza B infections depict distinct clinical pictures in ferrets.

    PubMed

    Huang, Stephen S H; Banner, David; Fang, Yuan; Ng, Derek C K; Kanagasabai, Thirumagal; Kelvin, David J; Kelvin, Alyson A

    2011-01-01

    Influenza A and B infections are a worldwide health concern to both humans and animals. High genetic evolution rates of the influenza virus allow the constant emergence of new strains and cause illness variation. Since human influenza infections are often complicated by secondary factors such as age and underlying medical conditions, strain or subtype specific clinical features are difficult to assess. Here we infected ferrets with 13 currently circulating influenza strains (including strains of pandemic 2009 H1N1 [H1N1pdm] and seasonal A/H1N1, A/H3N2, and B viruses). The clinical parameters were measured daily for 14 days in stable environmental conditions to compare clinical characteristics. We found that H1N1pdm strains had a more severe physiological impact than all season strains where pandemic A/California/07/2009 was the most clinically pathogenic pandemic strain. The most serious illness among seasonal A/H1N1 and A/H3N2 groups was caused by A/Solomon Islands/03/2006 and A/Perth/16/2009, respectively. Among the 13 studied strains, B/Hubei-Wujiagang/158/2009 presented the mildest clinical symptoms. We have also discovered that disease severity (by clinical illness and histopathology) correlated with influenza specific antibody response but not viral replication in the upper respiratory tract. H1N1pdm induced the highest and most rapid antibody response followed by seasonal A/H3N2, seasonal A/H1N1 and seasonal influenza B (with B/Hubei-Wujiagang/158/2009 inducing the weakest response). Our study is the first to compare the clinical features of multiple circulating influenza strains in ferrets. These findings will help to characterize the clinical pictures of specific influenza strains as well as give insights into the development and administration of appropriate influenza therapeutics.

  4. Enzymatic Formation of Apo-Carotenoids from the Xanthophyll Carotenoids Lutein, Zeaxanthin and β-Cryptoxanthin by Ferret Carotene-9’,10’-Monooxygenase

    PubMed Central

    Mein, Jonathan R.; Dolnikowski, Gregory G.; Ernst, Hansgeorg; Russell, Robert M.; Wang, Xiang-Dong

    2010-01-01

    Xanthophyll carotenoids, such as lutein, zeaxanthin and β-cryptoxanthin, may provide potential health benefits against chronic and degenerative diseases. Investigating pathways of xanthophyll metabolism are important to understanding their biological functions. Carotene-15,15’-monooxygenase (CMO1) has been shown to be involved in vitamin A formation, while recent studies suggest that carotene-9’,10’-monooxygenase (CMO2) may have a broader substrate specificity than previously recognized. In this in vitro study, we investigated baculovirus-generated recombinant ferret CMO2 cleavage activity towards the carotenoid substrates zeaxanthin, lutein and β-cryptoxanthin. Utilizing HPLC, LC-MS and GC-MS, we identified both volatile and non-volatile apocarotenoid products including 3-OH-β-ionone, 3-OH-α-ionone, β-ionone, 3-OH-α-apo-10’-carotenal, 3-OH-β-apo-10’-carotenal, and β-apo-10’-carotenal, indicating cleavage at both the 9,10 and 9’,10’ carbon-carbon double bond. Enzyme kinetic analysis indicated the xanthophylls zeaxanthin and lutein are preferentially cleaved over β-cryptoxanthin, indicating a key role of CMO2 in non-provitamin A carotenoid metabolism. Furthermore, incubation of 3-OH-β-apo-10’-carotenal with CMO2 lysate resulted in the formation of 3-OH-β-ionone. In the presence of NAD+, in vitro incubation of 3-OH-β-apo-10’-carotenal with ferret hepatic homogenates formed 3-OH-β-apo-10’-carotenoic acid. Since apo-carotenoids serve as important signaling molecules in a variety of biological processes, enzymatic cleavage of xanthophylls by mammalian CMO2 represents a new avenue of research regarding vertebrate carotenoid metabolism and biological function. PMID:21081106

  5. Experimental adaptation of an influenza H5 haemagglutinin (HA) confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets

    PubMed Central

    Imai, Masaki; Watanabe, Tokiko; Hatta, Masato; Das, Subash C.; Ozawa, Makoto; Shinya, Kyoko; Zhong, Gongxun; Hanson, Anthony; Katsura, Hiroaki; Watanabe, Shinji; Li, Chengjun; Kawakami, Eiryo; Yamada, Shinya; Kiso, Maki; Suzuki, Yasuo; Maher, Eileen A.; Neumann, Gabriele

    2012-01-01

    Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host range determinant since it mediates virus binding to host-specific cellular receptors1–3. Here, we therefore assessed the molecular changes in HA that would allow an H5 HA-possessing virus to transmit among mammals. We identified a reassortant virus with H5 HA possessing four mutations in a 2009 pandemic H1N1 virus backbone capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but it was not highly pathogenic and did not cause mortality. These results suggest that H5 HA can convert to an HA that supports efficient viral transmission in mammals. However, we do not know whether the four mutations in the H5 HA identified in this study would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral genes may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian-human reassortant viruses as tested here, may emerge. Our findings emphasize the need for pandemic preparedness for H5 HA-possessing viruses and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production, and distribution of effective countermeasures. PMID:22722205

  6. Comparison of the protection of ferrets against pandemic 2009 influenza A virus (H1N1) by 244 DI influenza virus and oseltamivir

    PubMed Central

    Dimmock, Nigel J.; Dove, Brian K.; Meng, Bo; Scott, Paul D.; Taylor, Irene; Cheung, Linda; Hallis, Bassam; Marriott, Anthony C.; Carroll, Miles W.; Easton, Andrew J.

    2012-01-01

    The main antivirals employed to combat seasonal and pandemic influenza are oseltamivir and zanamivir which act by inhibiting the virus-encoded neuraminidase. These have to be deployed close to the time of infection and antiviral resistance to the more widely used oseltamivir has arisen relatively rapidly. Defective interfering (DI) influenza virus is a natural antiviral that works in a different way to oseltamivir and zanamivir, and a cloned version (segment 1 244 DI RNA in a cloned A/PR/8/34 virus; 244/PR8) has proved effective in preclinical studies in mice. The active principle is the DI RNA, and this is thought to interact with all influenza A viruses by inhibiting RNA virus synthesis and packaging of the cognate virion RNA into nascent DI virus particles. We have compared the ability of DI virus and oseltamivir to protect ferrets from intranasal 2009 pandemic influenza virus A/California/04/09 (A/Cal, H1N1). Ferrets were treated with a single 2 μg intranasal dose of 244 DI RNA delivered as 244/PR8 virus, or a total of 25 mg/kg body weight of oseltamivir given as 10 oral doses over 5 days. Both DI virus and oseltamivir reduced day 2 infectivity and the influx of cells into nasal fluids, and permitted the development of adaptive immunity. However DI virus, but not oseltamivir, significantly reduced weight loss, facilitated better weight gain, reduced respiratory disease, and reduced infectivity on days 4 and 6. 244 DI RNA was amplified by A/Cal by >25,000-fold, consistent with the amelioration of clinical disease. Treatment with DI virus did not delay clearance or cause persistence of infectious virus or DI RNA. Thus in this system DI virus was overall more effective than oseltamivir in combatting pandemic A/California/04/09. PMID:23041142

  7. Heterogeneous pathological outcomes after experimental pH1N1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung.

    PubMed

    Vidaña, Beatriz; Martínez, Jorge; Martínez-Orellana, Pamela; García Migura, Lourdes; Montoya, María; Martorell, Jaime; Majó, Natàlia

    2014-01-01

    The swine-origin pandemic (p) H1N1 influenza A virus causes mild upper-respiratory tract disease in most human patients. However, some patients developed severe lower-respiratory tract infections with fatal consequences, and the cause of these infections remain unknown. Recently, it has been suggested that different populations have different degrees of susceptibility to pH1N1 strains due to host genetic variations that are associated with inappropriate immune responses against viral genetic characteristics. Here, we tested whether the pathologic patterns of influenza strains that produce different disease outcomes in humans could be reproduced in a ferret model. Our results revealed that the severities of infection did not correspond to particular viral isolate and were not associated with the clinical phenotypes of the corresponding patients. Severe pathological outcomes were associated with higher viral replication, especially in alveolar areas, and with an exacerbated innate cellular immune response that was characterised by substantial phagocytic and cytotoxic cell migration into the lungs. Moreover, detrimental innate cellular responses were linked to the up-regulation of several proinflammatory cytokines and chemokines and the down-regulation of IFNα in the lungs. Additionally, severe lung lesions were associated with greater up-regulations of pro-apoptotic markers and higher levels of apoptotic neutrophils and macrophages. In conclusion, this study confirmed that the clinicopathological outcomes of pH1N1 infection in ferrets were not only due to viral replication abilities but also depended on the hosts' capacities to mount efficient immune responses to control viral infection of the lung.

  8. Recent H1N1 viruses (A/USSR/90/77, A/Fiji/15899/83, A/Firenze/13/83) replicate poorly in ferret bronchial epithelium. Brief report.

    PubMed

    Sweet, C; Bird, R A; Coates, D M; Overton, H A; Smith, H

    1985-01-01

    Three recent wild-type H1N1 influenza virus isolates (A/USSR/90/77, A/Fiji/15899/83 and A/Firenze/13/83) replicated poorly in organ cultures of ferret bronchial tissue compared with the replication of an H3N2 wild-type virus (A/England/939/69). All four viruses replicated well in nasal turbinate tissue. Examination of one H1N1 virus (A/USSR/90/77) in vivo showed heavy infection in the upper respiratory tract of ferrets but little in the lower respiratory tract. These results raise the possibility that the mildness of human influenza arising from the H1N1 strains may be due to lack of capacity to attack the lower respiratory tract as well as the presence of antibody in previously exposed persons.

  9. Effects of 6-month daily supplementation with oral beta-carotene in combination or not with benzo[a]pyrene on cell-cycle markers in the lung of ferrets.

    PubMed

    Fuster, Antonia; Picó, Catalina; Sánchez, Juana; Oliver, Paula; Zingaretti, Maria Cristina; Murano, Incoronata; Morroni, Manrico; Hoeller, Ulrich; Goralczyk, Regina; Cinti, Saverio; Palou, Andreu

    2008-05-01

    Epidemiological studies have demonstrated that people who eat more fruits and vegetables (rich in carotenoids) and people who have higher serum beta-carotene (BC) levels have a lower risk of cancer, particularly lung cancer. However, the two main human intervention studies of BC supplementation (the ATBC and the CARET trials) revealed an increased risk of lung cancer among smokers and asbestos workers. Previous studies carried out in the ferret have reported that BC effects are related to dose. Here, we treated ferrets with two concentrations of oral BC (0.8 and 3.2 mg/kg body weight per day) for 6 months, using BC in a formulation also containing dl-alpha-tocopherol and ascorbyl palmitate. The effect of the smoke-derived carcinogenic agent benzo[a]pyrene (BP), with or without low-dose BC, was also analysed. We determined the protein levels and mRNA expression levels of activator protein 1 (c-Jun and c-Fos), c-Myc, cyclin D1, proliferating cellular nuclear antigen and retinoic acid receptor beta. We did not find higher levels of cell proliferation markers in the lung of ferrets treated with BC or signals of squamous metaplasia lesions either. On the other hand, although no evident signals of pulmonary carcinogenesis were observed in animals exposed to BP, BC supplementation in these animals may prevent against excess cell proliferation, since this reestablishes Jun protein and cyclin D1 mRNA levels in the lung of BP-exposed animals. In summary, these results show that the combination of BC with alpha-tocopherol and ascorbyl palmitate does not induce pro-oxidant effects in the lung of ferrets.

  10. Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not Exhibit Evidence of Original Antigenic Sin after Infection or Vaccination with the 2009 Pandemic H1N1 Influenza Virus

    PubMed Central

    O'Donnell, Christopher D.; Wright, Amber; Vogel, Leatrice; Boonnak, Kobporn; Treanor, John J.

    2014-01-01

    The hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus. PMID:24648486

  11. Profile of Antiemetic Activity of Netupitant Alone or in Combination with Palonosetron and Dexamethasone in Ferrets and Suncus murinus (House Musk Shrew)

    PubMed Central

    Rudd, John A.; Ngan, Man P.; Lu, Zengbing; Higgins, Guy A.; Giuliano, Claudio; Lovati, Emanuela; Pietra, Claudio

    2016-01-01

    Background and Aims: Chemotherapy-induced acute and delayed emesis involves the activation of multiple pathways, with 5-hydroxytryptamine (5-HT; serotonin) playing a major role in the initial response. Substance P tachykinin NK1 receptor antagonists can reduce emesis induced by disparate emetic challenges and therefore have a clinical utility as broad inhibitory anti-emetic drugs. In the present studies, we investigate the broad inhibitory anti-emetic profile of a relatively new NK1 receptor antagonist, netupitant, alone or in combination with the long acting 5-HT3 receptor antagonist, palonosetron, for a potential to reduce emesis in ferrets and shrews. Materials and Methods: Ferrets were pretreated with netupitant and/or palonosetron, and then administered apomorphine (0.125 mg/kg, s.c.), morphine (0.5 mg/kg, s.c.), ipecacuanha (1.2 mg/kg, p.o.), copper sulfate (100 mg/kg, intragastric), or cisplatin (5–10 mg/kg, i.p.); in other studies netupitant was administered to Suncus murinus before motion (4 cm horizontal displacement, 2 Hz for 10 min). Results: Netupitant (3 mg/kg, p.o.) abolished apomorphine-, morphine-, ipecacuanha- and copper sulfate-induced emesis. Lower doses of netupitant (0.03–0.3 mg/kg, p.o.) dose-dependently reduced cisplatin (10 mg/kg, i.p.)-induced emesis in an acute (8 h) model, and motion-induced emesis in S. murinus. In a ferret cisplatin (5 mg/kg, i.p.)-induced acute and delayed emesis model, netupitant administered once at 3 mg/kg, p.o., abolished the first 24 h response and reduced the 24–72 h response by 94.6%; the reduction was markedly superior to the effect of a three times per day administration of ondansetron (1 mg/kg, i.p.). A single administration of netupitant (1 mg/kg, p.o.) plus palonosetron (0.1 mg/kg, p.o.) combined with dexamethasone (1 mg/kg, i.p., once per day), also significantly antagonized cisplatin-induced acute and delayed emesis and was comparable with a once-daily regimen of ondansetron (1 mg/kg, p.o.) plus

  12. Profile of Antiemetic Activity of Netupitant Alone or in Combination with Palonosetron and Dexamethasone in Ferrets and Suncus murinus (House Musk Shrew)

    PubMed Central

    Rudd, John A.; Ngan, Man P.; Lu, Zengbing; Higgins, Guy A.; Giuliano, Claudio; Lovati, Emanuela; Pietra, Claudio

    2016-01-01

    Background and Aims: Chemotherapy-induced acute and delayed emesis involves the activation of multiple pathways, with 5-hydroxytryptamine (5-HT; serotonin) playing a major role in the initial response. Substance P tachykinin NK1 receptor antagonists can reduce emesis induced by disparate emetic challenges and therefore have a clinical utility as broad inhibitory anti-emetic drugs. In the present studies, we investigate the broad inhibitory anti-emetic profile of a relatively new NK1 receptor antagonist, netupitant, alone or in combination with the long acting 5-HT3 receptor antagonist, palonosetron, for a potential to reduce emesis in ferrets and shrews. Materials and Methods: Ferrets were pretreated with netupitant and/or palonosetron, and then administered apomorphine (0.125 mg/kg, s.c.), morphine (0.5 mg/kg, s.c.), ipecacuanha (1.2 mg/kg, p.o.), copper sulfate (100 mg/kg, intragastric), or cisplatin (5–10 mg/kg, i.p.); in other studies netupitant was administered to Suncus murinus before motion (4 cm horizontal displacement, 2 Hz for 10 min). Results: Netupitant (3 mg/kg, p.o.) abolished apomorphine-, morphine-, ipecacuanha- and copper sulfate-induced emesis. Lower doses of netupitant (0.03–0.3 mg/kg, p.o.) dose-dependently reduced cisplatin (10 mg/kg, i.p.)-induced emesis in an acute (8 h) model, and motion-induced emesis in S. murinus. In a ferret cisplatin (5 mg/kg, i.p.)-induced acute and delayed emesis model, netupitant administered once at 3 mg/kg, p.o., abolished the first 24 h response and reduced the 24–72 h response by 94.6%; the reduction was markedly superior to the effect of a three times per day administration of ondansetron (1 mg/kg, i.p.). A single administration of netupitant (1 mg/kg, p.o.) plus palonosetron (0.1 mg/kg, p.o.) combined with dexamethasone (1 mg/kg, i.p., once per day), also significantly antagonized cisplatin-induced acute and delayed emesis and was comparable with a once-daily regimen of ondansetron (1 mg/kg, p.o.) plus

  13. Predicting Disease Severity and Viral Spread of H5N1 Influenza Virus in Ferrets in the Context of Natural Exposure Routes

    PubMed Central

    Edenborough, Kathryn M.; Lowther, Suzanne; Laurie, Karen; Yamada, Manabu; Long, Fenella; Bingham, John; Payne, Jean; Harper, Jennifer; Haining, Jessica; Arkinstall, Rachel; Gilbertson, Brad; Middleton, Deborah

    2015-01-01

    ABSTRACT Although avian H5N1 influenza virus has yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the World Health Organization (WHO) has developed a risk categorization for different levels of exposure to environmental, poultry, or human sources of infection. While these take into account the infection source, they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this could affect the disease outcome. Knowledge of the kinetics and spread of virus after natural routes of exposure may further inform the risk of infection, as well as the likely disease severity. Using the ferret model of H5N1 infection, we compared the commonly used but artificial inoculation method that saturates the total respiratory tract (TRT) with virus to upper respiratory tract (URT) and oral routes of delivery, those likely to be encountered by humans in nature. We show that there was no statistically significant difference in survival rate with the different routes of infection, but the disease characteristics were somewhat different. Following URT infection, viral spread to systemic organs was comparatively delayed and more focal than after TRT infection. By both routes, severe disease was associated with early viremia and central nervous system infection. After oral exposure to the virus, mild infections were common suggesting consumption of virus-contaminated liquids may be associated with seroconversion in the absence of severe disease. IMPORTANCE Risks for human H5N1 infection include direct contact with infected birds and frequenting contaminated environments. We used H5N1 ferret infection models to show that breathing in the virus was more likely to produce clinical infection than swallowing contaminated

  14. Effect of varying the intensity and train frequency of forelimb and cerebellar mossy fiber conditioned stimuli on the latency of conditioned eye-blink responses in decerebrate ferrets.

    PubMed

    Svensson, P; Ivarsson, M; Hesslow, G

    1997-01-01

    To study the role of the mossy fiber afferents to the cerebellum in classical eye-blink conditioning, in particular the timing of the conditioned responses, we compared the effects of varying a peripheral conditioned stimulus with the effects of corresponding variations of direct stimulation of the mossy fibers. In one set of experiments, decerebrate ferrets were trained in a Pavlovian eye-blink conditioning paradigm with electrical forelimb train stimulation as conditioned stimulus and electrical periorbital stimulation as the unconditioned stimulus. When stable conditioning had been achieved, the effect of increasing the intensity or frequency of the forelimb stimulation was tested. By increasing the intensity from 1 to 2 mA, or the train frequency from 50 to 100 Hz, an immediate decrease was induced in both the onset latency and the latency to peak of the conditioned response. If the conditioned stimulus intensity/frequency was maintained at the higher level, the response latencies gradually returned to preshift values. In a second set of experiments, the forelimb stimulation was replaced by direct train stimulation of the middle cerebellar peduncle as conditioned stimulus. Varying the frequency of the stimulus train between 50 and 100 Hz had effects that were almost identical to those obtained when using a forelimb conditioned stimulus. The functional meaning of the latency effect is discussed. It is also suggested that the results support the view that the conditioned stimulus is transmitted through the mossy fibers and that the mechanism for timing the conditioned response is situated in the cerebellum.

  15. Intranasal vaccination with H5, H7 and H9 hemagglutinins co-localized in a virus-like particle protects ferrets from multiple avian influenza viruses.

    PubMed

    Tretyakova, Irina; Pearce, Melissa B; Florese, Ruth; Tumpey, Terrence M; Pushko, Peter

    2013-07-20

    Avian influenza H5, H7 and H9 viruses top the World Health Organization's (WHO) list of subtypes with the greatest pandemic potential. Here we describe a recombinant virus-like particle (VLP) that co-localizes hemagglutinin (HA) proteins derived from H5N1, H7N2, and H9N2 viruses as an experimental vaccine against these viruses. A baculovirus vector was configured to co-express the H5, H7, and H9 genes from A/Viet Nam/1203/2004 (H5N1), A/New York/107/2003 (H7N2) and A/Hong Kong/33982/2009 (H9N2) viruses, respectively, as well as neuraminidase (NA) and matrix (M1) genes from A/Puerto Rico/8/1934 (H1N1) virus. Co-expression of these genes in Sf9 cells resulted in production of triple-subtype VLPs containing HA molecules derived from the three influenza viruses. The triple-subtype VLPs exhibited hemagglutination and neuraminidase activities and morphologically resembled influenza virions. Intranasal vaccination of ferrets with the VLPs resulted in induction of serum antibody responses and efficient protection against experimental challenges with H5N1, H7N2, and H9N2 viruses.

  16. Sodium/calcium exchange modulates intracellular calcium overload during posthypoxic reoxygenation in mammalian working myocardium. Evidence from aequorin-loaded ferret ventricular muscles.

    PubMed Central

    Kihara, Y; Sasayama, S; Inoko, M; Morgan, J P

    1994-01-01

    We tested the hypothesis that the intracellular Ca2+ overload of ventricular myocardium during the period of posthypoxic reoxygenation is mediated by transsarcolemmal Ca2+ influx via Na+/Ca2+ exchange. In aequorin-loaded, ferret right ventricular papillary muscles, blockers of the sarcolemmal and the sarcoplasmic reticulum Ca2+ channels, slowed the Cai2+ transient, producing a convex ascent during membrane depolarization, followed by a concave descent during repolarization. The magnitude of the Cai2+ transient was affected by changes in the membrane potential, Nai+, Nao+, and Cao2+, and was blocked by Ni2+, or dichlorbenzamil. The calculated Na+/Ca2+ exchange current was in the reverse mode (Ca2+ influx) during the ascending phase of the Cai2+ transient, and was abruptly switched to the forward mode (Ca2+ efflux) at repolarization, matching the time course of the Cai2+ transient. During hypoxic superfusion, the Cai2+ transient was abbreviated, which was associated with a shorter action potential duration. In contrast, immediately after reoxygenation, the Cai2+ transient increased to a level greater than that of the control, even though the action potential remained abbreviated. This is the first demonstration on a beat-to-beat basis that, during reoxygenation, Ca2+ influx via Na+/Ca2+ exchange is augmented and transports a significant amount of Ca2+ into the ventricular myocardial cell. The activation of the exchanger at the time of reoxygenation appears to be mediated by Nai+ accumulation, which occurs during hypoxia. PMID:8132766

  17. Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model.

    PubMed

    Otte, Anna; Marriott, Anthony C; Dreier, Carola; Dove, Brian; Mooren, Kyra; Klingen, Thorsten R; Sauter, Martina; Thompson, Katy-Anne; Bennett, Allan; Klingel, Karin; van Riel, Debby; McHardy, Alice C; Carroll, Miles W; Gabriel, Gülsah

    2016-06-24

    There is increasing evidence that 2009 pandemic H1N1 influenza viruses have evolved after pandemic onset giving rise to severe epidemics in subsequent waves. However, it still remains unclear which viral determinants might have contributed to disease severity after pandemic initiation. Here, we show that distinct mutations in the 2009 pandemic H1N1 virus genome have occurred with increased frequency after pandemic declaration. Among those, a mutation in the viral hemagglutinin was identified that increases 2009 pandemic H1N1 virus binding to human-like α2,6-linked sialic acids. Moreover, these mutations conferred increased viral replication in the respiratory tract and elevated respiratory droplet transmission between ferrets. Thus, our data show that 2009 H1N1 influenza viruses have evolved after pandemic onset giving rise to novel virus variants that enhance viral replicative fitness and respiratory droplet transmission in a mammalian animal model. These findings might help to improve surveillance efforts to assess the pandemic risk by emerging influenza viruses.

  18. Evolution of 2009 H1N1 influenza viruses during the pandemic correlates with increased viral pathogenicity and transmissibility in the ferret model

    PubMed Central

    Otte, Anna; Marriott, Anthony C.; Dreier, Carola; Dove, Brian; Mooren, Kyra; Klingen, Thorsten R.; Sauter, Martina; Thompson, Katy-Anne; Bennett, Allan; Klingel, Karin; van Riel, Debby; McHardy, Alice C.; Carroll, Miles W.; Gabriel, Gülsah

    2016-01-01

    There is increasing evidence that 2009 pandemic H1N1 influenza viruses have evolved after pandemic onset giving rise to severe epidemics in subsequent waves. However, it still remains unclear which viral determinants might have contributed to disease severity after pandemic initiation. Here, we show that distinct mutations in the 2009 pandemic H1N1 virus genome have occurred with increased frequency after pandemic declaration. Among those, a mutation in the viral hemagglutinin was identified that increases 2009 pandemic H1N1 virus binding to human-like α2,6-linked sialic acids. Moreover, these mutations conferred increased viral replication in the respiratory tract and elevated respiratory droplet transmission between ferrets. Thus, our data show that 2009 H1N1 influenza viruses have evolved after pandemic onset giving rise to novel virus variants that enhance viral replicative fitness and respiratory droplet transmission in a mammalian animal model. These findings might help to improve surveillance efforts to assess the pandemic risk by emerging influenza viruses. PMID:27339001

  19. Three-dimensional fibre-type distribution in the paravertebral muscles of the domestic ferret (Mustela putorius f. furo) with relation to functional demands during locomotion.

    PubMed

    Moritz, Sabine; Fischer, Martin S; Schilling, Nadja

    2007-01-01

    We investigated the functional corollaries of a relatively long trunk with regard to trunk use during overground and underground locomotion and with regard to fibre-type distribution within the paravertebral musculature using the example of the domestic ferret. Fibre-type distribution was determined using enzyme histochemistry on serial cross-sections through the complete musculo-skeletal apparatus. Back posture and back movements were analysed using cineradiography. During overground locomotion, the back is bent into an arch, resulting in a back length comparable to normally proportioned small mammals. During underground locomotion, the back is held straight, resulting in greater rotational inertia and higher stabilisation requirements. This is reflected in the fibre-type distribution pattern, which differs clearly from that of all other mammals investigated so far. Instead of being separated into superficial, glycolytic and deep, oxidative parts, all the epaxial and the iliopsoas muscles consisted of 20-30% oxidative, 20-30% oxidative-glycolytic and 40-60% glycolytic fibres, with no or only minor differences between superficial and profound muscles or muscle regions. Only the quadratus lumborum muscle showed a fibre-type distribution comparable to other mammals, reflecting its primary function as an accessory muscle of respiration. We suggest that the observed pattern reflects the adaptation of the back muscles to the functional demands of a long trunk and the increased need to stabilise it during overground and especially underground locomotion. PMID:17512707

  20. Emergence of a sylvatic enzootic formosan ferret badger-associated rabies in Taiwan and the geographical separation of two phylogenetic groups of rabies viruses.

    PubMed

    Tsai, K J; Hsu, W C; Chuang, W C; Chang, J C; Tu, Y C; Tsai, H J; Liu, H F; Wang, F I; Lee, S H

    2016-01-01

    Taiwan had been declared rabies-free in humans and domestic animals for five decades until July 2013, when surprisingly, three Formosan ferret badgers (FB) were diagnosed with rabies. Since then, a variety of wild carnivores and other wildlife species have been found dead, neurologically ill, or exhibiting aggressive behaviors around the island. To determine the affected animal species, geographic areas, and environments, animal bodies were examined for rabies by direct fluorescent antibody test (FAT). The viral genomes from the brains of selected rabid animals were sequenced for the phylogeny of rabies viruses (RABV). Out of a total of 1016 wild carnivores, 276/831 (33.2%) Formosan FBs were FAT positive, with occasional biting incidents in 1 dog and suspected spillover in 1 house shrew. All other animals tested, including dogs, cats, bats, mice, house shrews, and squirrels, were rabies-negative. The rabies was badger-associated and confined to nine counties/cities in sylvatic environments. Phylogeny of nucleoprotein and glycoprotein genes from 59 Formosan FB-associated RABV revealed them to be clustered in two distinct groups, TWI and TWII, consistent with the geographic segregation into western and eastern Taiwan provided by the Central Mountain Range and into northern rabies-free and central-southern rabies-affected regions by a river bisecting western Taiwan. The unique features of geographic and genetic segregation, sylvatic enzooticity, and FB-association of RABV suggest a logical strategy for the control of rabies in this nation.

  1. Emergence of a sylvatic enzootic formosan ferret badger-associated rabies in Taiwan and the geographical separation of two phylogenetic groups of rabies viruses.

    PubMed

    Tsai, K J; Hsu, W C; Chuang, W C; Chang, J C; Tu, Y C; Tsai, H J; Liu, H F; Wang, F I; Lee, S H

    2016-01-01

    Taiwan had been declared rabies-free in humans and domestic animals for five decades until July 2013, when surprisingly, three Formosan ferret badgers (FB) were diagnosed with rabies. Since then, a variety of wild carnivores and other wildlife species have been found dead, neurologically ill, or exhibiting aggressive behaviors around the island. To determine the affected animal species, geographic areas, and environments, animal bodies were examined for rabies by direct fluorescent antibody test (FAT). The viral genomes from the brains of selected rabid animals were sequenced for the phylogeny of rabies viruses (RABV). Out of a total of 1016 wild carnivores, 276/831 (33.2%) Formosan FBs were FAT positive, with occasional biting incidents in 1 dog and suspected spillover in 1 house shrew. All other animals tested, including dogs, cats, bats, mice, house shrews, and squirrels, were rabies-negative. The rabies was badger-associated and confined to nine counties/cities in sylvatic environments. Phylogeny of nucleoprotein and glycoprotein genes from 59 Formosan FB-associated RABV revealed them to be clustered in two distinct groups, TWI and TWII, consistent with the geographic segregation into western and eastern Taiwan provided by the Central Mountain Range and into northern rabies-free and central-southern rabies-affected regions by a river bisecting western Taiwan. The unique features of geographic and genetic segregation, sylvatic enzooticity, and FB-association of RABV suggest a logical strategy for the control of rabies in this nation. PMID:26711025

  2. NB protein does not affect influenza B virus replication in vitro and is not required for replication in or transmission between ferrets.

    PubMed

    Elderfield, Ruth A; Koutsakos, Marios; Frise, Rebecca; Bradley, Konrad; Ashcroft, Jonathan; Miah, Shanhjahan; Lackenby, Angie; Barclay, Wendy S

    2016-03-01

    The influenza B virus encodes a unique protein, NB, a membrane protein whose function in the replication cycle is not, as yet, understood. We engineered a recombinant influenza B virus lacking NB expression, with no concomitant difference in expression or activity of viral neuraminidase (NA) protein, an important caveat since NA is encoded on the same segment and initiated from a start codon just 4 nt downstream of NB. Replication of the virus lacking NB was not different to wild-type virus with full-length NB in clonal immortalized or complex primary cell cultures. In the mouse model, virus lacking NB induced slightly lower IFN-α levels in infected lungs, but this did not affect virus titres or weight loss. In ferrets infected with a mixture of viruses that did or did not express NB, there was no fitness advantage for the virus that retained NB. Moreover, virus lacking NB protein was transmitted following respiratory droplet exposure of sentinel animals. These data suggest no role for NB in supporting replication or transmission in vivo in this animal model. The role of NB and the nature of selection to retain it in all natural influenza B viruses remain unclear. PMID:26703440

  3. The Homologous Tripartite Viral RNA Polymerase of A/Swine/Korea/CT1204/2009(H1N2) Influenza Virus Synergistically Drives Efficient Replication and Promotes Respiratory Droplet Transmission in Ferrets

    PubMed Central

    Pascua, Philippe Noriel Q.; Song, Min-Suk; Kwon, Hyeok-Il; Lim, Gyo-Jin; Kim, Eun-Ha; Park, Su-Jin; Lee, Ok-Jun; Kim, Chul-Joong; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    We previously reported that influenza A/swine/Korea/1204/2009(H1N2) virus was virulent and transmissible in ferrets in which the respiratory-droplet-transmissible virus (CT-Sw/1204) had acquired simultaneous hemagglutinin (HAD225G) and neuraminidase (NAS315N) mutations. Incorporating these mutations into the nonpathogenic A/swine/Korea/1130/2009(H1N2, Sw/1130) virus consequently altered pathogenicity and growth in animal models but could not establish efficient transmission or noticeable disease. We therefore exploited various reassortants of these two viruses to better understand and identify other viral factors responsible for pathogenicity, transmissibility, or both. We found that possession of the CT-Sw/1204 tripartite viral polymerase enhanced replicative ability and pathogenicity in mice more significantly than did expression of individual polymerase subunit proteins. In ferrets, homologous expression of viral RNA polymerase complex genes in the context of the mutant Sw/1130 carrying the HA225G and NA315N modifications induced optimal replication in the upper nasal and lower respiratory tracts and also promoted efficient aerosol transmission to respiratory droplet contact ferrets. These data show that the synergistic function of the tripartite polymerase gene complex of CT-Sw/1204 is critically important for virulence and transmission independent of the surface glycoproteins. Sequence comparison results reveal putative differences that are likely to be responsible for variation in disease. Our findings may help elucidate previously undefined viral factors that could expand the host range and disease severity induced by triple-reassortant swine viruses, including the A(H1N1)pdm09 virus, and therefore further justify the ongoing development of novel antiviral drugs targeting the viral polymerase complex subunits. PMID:23864624

  4. Evaluation of the attenuation, immunogenicity, and efficacy of a live virus vaccine generated by codon-pair bias de-optimization of the 2009 pandemic H1N1 influenza virus, in ferrets.

    PubMed

    Broadbent, Andrew J; Santos, Celia P; Anafu, Amanda; Wimmer, Eckard; Mueller, Steffen; Subbarao, Kanta

    2016-01-20

    Codon-pair bias de-optimization (CPBD) of viruses involves re-writing viral genes using statistically underrepresented codon pairs, without any changes to the amino acid sequence or codon usage. Previously, this technology has been used to attenuate the influenza A/Puerto Rico/8/34 (H1N1) virus. The de-optimized virus was immunogenic and protected inbred mice from challenge. In order to assess whether CPBD could be used to produce a live vaccine against a clinically relevant influenza virus, we generated an influenza A/California/07/2009 pandemic H1N1 (2009 pH1N1) virus with de-optimized HA and NA gene segments (2009 pH1N1-(HA+NA)(Min)), and evaluated viral replication and protein expression in MDCK cells, and attenuation, immunogenicity, and efficacy in outbred ferrets. The 2009 pH1N1-(HA+NA)(Min) virus grew to a similar titer as the 2009 pH1N1 wild type (wt) virus in MDCK cells (∼10(6)TCID50/ml), despite reduced HA and NA protein expression on western blot. In ferrets, intranasal inoculation of 2009 pH1N1-(HA+NA)(Min) virus at doses ranging from 10(3) to 10(5) TCID50 led to seroconversion in all animals and protection from challenge with the 2009 pH1N1 wt virus 28 days later. The 2009 pH1N1-(HA+NA)(Min) virus did not cause clinical illness in ferrets, but replicated to a similar titer as the wt virus in the upper and lower respiratory tract, suggesting that de-optimization of additional gene segments may be warranted for improved attenuation. Taken together, our data demonstrate the potential of using CPBD technology for the development of a live influenza virus vaccine if the level of attenuation is optimized. PMID:26655630

  5. A Single Dose of an Avian H3N8 Influenza Virus Vaccine Is Highly Immunogenic and Efficacious against a Recently Emerged Seal Influenza Virus in Mice and Ferrets

    PubMed Central

    Baz, Mariana; Paskel, Myeisha; Matsuoka, Yumiko; Zengel, James R.; Cheng, Xing; Treanor, John J.; Jin, Hong

    2015-01-01

    ABSTRACT H3N8 influenza viruses are a commonly found subtype in wild birds, usually causing mild or no disease in infected birds. However, they have crossed the species barrier and have been associated with outbreaks in dogs, pigs, donkeys, and seals and therefore pose a threat to humans. A live attenuated, cold-adapted (ca) H3N8 vaccine virus was generated by reverse genetics using the wild-type (wt) hemagglutinin (HA) and neuraminidase (NA) genes from the A/blue-winged teal/Texas/Sg-00079/2007 (H3N8) (tl/TX/079/07) wt virus and the six internal protein gene segments from the ca influenza A virus vaccine donor strain, A/Ann Arbor/6/60 ca (H2N2), the backbone of the licensed seasonal live attenuated influenza vaccine. One dose of the tl/TX/079/07 ca vaccine induced a robust neutralizing antibody response against the homologous (tl/TX/079/07) and two heterologous influenza viruses, including the recently emerged A/harbor seal/New Hampshire/179629/2011 (H3N8) and A/northern pintail/Alaska/44228-129/2006 (H3N8) viruses, and conferred robust protection against the homologous and heterologous influenza viruses. We also analyzed human sera against the tl/TX/079/07 H3N8 avian influenza virus and observed low but detectable antibody reactivity in elderly subjects, suggesting that older H3N2 influenza viruses confer some cross-reactive antibody. The latter observation was confirmed in a ferret study. The safety, immunogenicity, and efficacy of the tl/TX/079/07 ca vaccine in mice and ferrets support further evaluation of this vaccine in humans for use in the event of transmission of an H3N8 avian influenza virus to humans. The human and ferret serology data suggest that a single dose of the vaccine may be sufficient in older subjects. IMPORTANCE Although natural infection of humans with an avian H3N8 influenza virus has not yet been reported, this influenza virus subtype has already crossed the species barrier and productively infected mammals. Pandemic preparedness is an

  6. Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts.

    PubMed Central

    Kusuoka, H; Porterfield, J K; Weisman, H F; Weisfeldt, M L; Marban, E

    1987-01-01

    Contractile dysfunction in stunned myocardium could result from a decrease in the intracellular free [Ca2+] transient during each beat, a decrease in maximal Ca2+-activated force, or a shift in myofilament Ca2+ sensitivity. We measured developed pressure (DP) at several [Ca]0 (0.5-7.5 mM) in isovolumic Langendorff-perfused ferret hearts at 37 degrees C after 15 min of global ischemia (stunned group, n = 13) or in a nonischemic control group (n = 6). At all [Ca]0, DP was depressed in the stunned group (P less than 0.001). Maximal Ca2+-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was decreased after stunning (P less than 0.05). Normalization of the DP-[Ca]0 relationship by corresponding MCAP (Ca0 sensitivity) revealed a shift to higher [Ca]0 in stunned hearts. To test whether cellular Ca overload initiates stunning, we reperfused with low-[Ca]0 solution (0.1-0.5 mM; n = 8). DP and MCAP in the low-[Ca]0 group were comparable to control (P greater than 0.05), and higher than in the stunned group (P less than 0.05). Myocardial [ATP] observed by phosphorus NMR failed to correlate with functional recovery. In conclusion, contractile dysfunction in stunned myocardium is due to a decline in maximal force, and a shift in Ca0 sensitivity (which may reflect either decreased myofilament Ca2+ sensitivity or a decrease in the [Ca2+] transient). Our results also indicate that calcium entry upon reperfusion plays a major role in the pathogenesis of myocardial stunning. Images PMID:3818956

  7. Recombinant soluble, multimeric HA and NA exhibit distinctive types of protection against pandemic swine-origin 2009 A(H1N1) influenza virus infection in ferrets.

    PubMed

    Bosch, Berend Jan; Bodewes, Rogier; de Vries, Robert P; Kreijtz, Joost H C M; Bartelink, Willem; van Amerongen, Geert; Rimmelzwaan, Guus F; de Haan, Cornelis A M; Osterhaus, Albert D M E; Rottier, Peter J M

    2010-10-01

    The emergence and subsequent swift and global spread of the swine-origin influenza virus A(H1N1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. With this aim, we produced soluble, multimeric forms of the 2009 A(H1N1) HA (sHA(3)) and NA (sNA(4)) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. Immunization twice with 3.75-microg doses of these antigens elicited strong antibody responses, which were adjuvant dependent. Interestingly, coadministration of both antigens strongly enhanced the HA-specific but not the NA-specific responses. Distinct patterns of protection were observed upon challenge inoculation with the homologous H1N1 virus. Whereas vaccination with sHA(3) dramatically reduced virus replication (e.g., by lowering pulmonary titers by about 5 log(10) units), immunization with sNA(4) markedly decreased the clinical effects of infection, such as body weight loss and lung pathology. Clearly, optimal protection was achieved by the combination of the two antigens. Our observations demonstrate the great vaccine potential of multimeric HA and NA ectodomains, as these can be easily, rapidly, flexibly, and safely produced in high quantities. In particular, our study underscores the underrated importance of NA in influenza vaccination, which we found to profoundly and specifically contribute to protection by HA. Its inclusion in a vaccine is likely to reduce the HA dose required and to broaden the protective immunity.

  8. Acute alterations in the regulation of lipid metabolism after intravascular reexposure to a single bolus of homologous virus during influenza B infection in ferrets: possible model of epiphenomena associated with influenza.

    PubMed Central

    Kang, E. S.; Galloway, M. S.; Bean, W.; Cook, G. A.; Olson, G.

    1991-01-01

    Metabolic responses occurring 24 h following the secondary haematogenous dissemination of influenza B virus during convalescence from infection were examined in the ferret as a possible model for epiphenomena which can occur following infection with influenza. Among the major changes found were a further rise in the mean fasting serum free fatty acid (FFA) level to three times the control mean value and a 50% drop in the mean serum triglyceride (TG) concentration after the intravascular administration of a single bolus of virus compared to levels found in uninfected or convalescent animals. In adipose tissue, hormone-sensitive and lipoprotein lipase activities were increased six and three-fold, respectively, over mean control values, probably accounting for the changes that were observed in serum lipid concentrations. In the liver, total carnitine palmitoyltransferase (CPT) activity was affected only slightly and the total lipid content of the liver remained unchanged. These findings indicate that 24 h after the intravascular dissemination of homologous virus in a single bolus during convalescence from influenza B infection, major distortions in the regulation of lipid metabolism occur in the ferret. Loss of the synchronous regulation of the two adipose tissue lipases is a significant consequence leading to the mobilization of a large amount of FFA during fasting from both adipose tissue and the circulating plasma TG stores. PMID:1843259

  9. Development of a High-Yield Live Attenuated H7N9 Influenza Virus Vaccine That Provides Protection against Homologous and Heterologous H7 Wild-Type Viruses in Ferrets

    PubMed Central

    Baz, Mariana; Lu, Janine; Paskel, Myeisha; Santos, Celia; Subbarao, Kanta; Jin, Hong; Matsuoka, Yumiko

    2014-01-01

    ABSTRACT Live attenuated H7N9 influenza vaccine viruses that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the newly emerged wild-type (wt) A/Anhui/1/2013 (H7N9) and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (AA ca) were generated by reverse genetics. The reassortant virus containing the original wt A/Anhui/1/2013 HA and NA sequences replicated poorly in eggs. Multiple variants with amino acid substitutions in the HA head domain that improved viral growth were identified by viral passage in eggs and MDCK cells. The selected vaccine virus containing two amino acid changes (N133D/G198E) in the HA improved viral titer by more than 10-fold (reached a titer of 108.6 fluorescent focus units/ml) without affecting viral antigenicity. Introduction of these amino acid changes into an H7N9 PR8 reassortant virus also significantly improved viral titers and HA protein yield in eggs. The H7N9 ca vaccine virus was immunogenic in ferrets. A single dose of vaccine conferred complete protection of ferrets from homologous wt A/Anhui/1/2013 (H7N9) and nearly complete protection from heterologous wt A/Netherlands/219/2003 (H7N7) challenge infection. Therefore, this H7N9 live attenuated influenza vaccine (LAIV) candidate has been selected for vaccine manufacture and clinical evaluation to protect humans from wt H7N9 virus infection. IMPORTANCE In response to the recent avian H7N9 influenza virus infection in humans, we developed a live attenuated H7N9 influenza vaccine (LAIV) with two amino acid substitutions in the viral HA protein that improved vaccine yield by 10-fold in chicken embryonated eggs, the substrate for vaccine manufacture. The two amino acids also improved the antigen yield for inactivated H7N9 vaccines, demonstrating that this finding could great facilitate the efficiency of H7N9 vaccine manufacture. The candidate H7N9 LAIV was immunogenic and protected ferrets against homologous and heterologous

  10. Matrix M H5N1 Vaccine Induces Cross-H5 Clade Humoral Immune Responses in a Randomized Clinical Trial and Provides Protection from Highly Pathogenic Influenza Challenge in Ferrets

    PubMed Central

    Cox, Rebecca J.; Major, Diane; Pedersen, Gabriel; Pathirana, Rishi D.; Hoschler, Katja; Guilfoyle, Kate; Roseby, Sarah; Bredholt, Geir; Assmus, Jörg; Breakwell, Lucy; Campitelli, Laura; Sjursen, Haakon

    2015-01-01

    Background and Methods Highly pathogenic avian influenza (HPAI) viruses constitute a pandemic threat and the development of effective vaccines is a global priority. Sixty adults were recruited into a randomized clinical trial and were intramuscularly immunized with two virosomal vaccine H5N1 (NIBRG-14) doses (21 days apart) of 30μg HA alone or 1.5, 7.5 or 30μg HA adjuvanted with Matrix M. The kinetics and longevity of the serological responses against NIBRG-14 were determined by haemagglutination inhibition (HI), single radial haemolysis (SRH), microneutralization (MN) and ELISA assays. The cross-H5 clade responses in sera were determined by HI and the antibody-secreting (ASC) cell ELISPOT assays. The protective efficacy of the vaccine against homologous HPAI challenge was evaluated in ferrets. Results The serological responses against the homologous and cross-reactive strains generally peaked one week after the second dose, and formulation with Matrix M augmented the responses. The NIBRG-14-specific seroprotection rates fell significantly by six months and were low against cross-reactive strains although the adjuvant appeared to prolong the longevity of the protective responses in some subjects. By 12 months post-vaccination, nearly all vaccinees had NIBRG-14-specific antibody titres below the protective thresholds. The Matrix M adjuvant was shown to greatly improve ASC and serum IgG responses following vaccination. In a HPAI ferret challenge model, the vaccine protected the animals from febrile responses, severe weight loss and local and systemic spread of the virus. Conclusion Our findings show that the Matrix M-adjuvanted virosomal H5N1 vaccine is a promising pre-pandemic vaccine candidate. Trial Registration ClinicalTrials.gov NCT00868218 PMID:26147369

  11. Oligomeric Recombinant H5 HA1 Vaccine Produced in Bacteria Protects Ferrets from Homologous and Heterologous Wild-Type H5N1 Influenza Challenge and Controls Viral Loads Better than Subunit H5N1 Vaccine by Eliciting High-Affinity Antibodies

    PubMed Central

    Verma, Swati; Dimitrova, Milena; Munjal, Ashok; Fontana, Juan; Crevar, Corey J.; Carter, Donald M.; Ross, Ted M.

    2012-01-01

    Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission. PMID:22951833

  12. Contemporary Seasonal Influenza A (H1N1) Virus Infection Primes for a More Robust Response To Split Inactivated Pandemic Influenza A (H1N1) Virus Vaccination in Ferrets

    PubMed Central

    Ellebedy, Ali H.; Fabrizio, Thomas P.; Kayali, Ghazi; Oguin, Thomas H.; Brown, Scott A.; Rehg, Jerold; Thomas, Paul G.; Webby, Richard J.

    2010-01-01

    Human influenza pandemics occur when influenza viruses to which the population has little or no immunity emerge and acquire the ability to achieve human-to-human transmission. In April 2009, cases of a novel H1N1 influenza virus in children in the southwestern United States were reported. It was retrospectively shown that these cases represented the spread of this virus from an ongoing outbreak in Mexico. The emergence of the pandemic led to a number of national vaccination programs. Surprisingly, early human clinical trial data have shown that a single dose of nonadjuvanted pandemic influenza A (H1N1) 2009 monovalent inactivated vaccine (pMIV) has led to a seroprotective response in a majority of individuals, despite earlier studies showing a lack of cross-reactivity between seasonal and pandemic H1N1 viruses. Here we show that previous exposure to a contemporary seasonal H1N1 influenza virus and to a lesser degree a seasonal influenza virus trivalent inactivated vaccine is able to prime for a higher antibody response after a subsequent dose of pMIV in ferrets. The more protective response was partially dependent on the presence of CD8+ cells. Two doses of pMIV were also able to induce a detectable antibody response that provided protection from subsequent challenge. These data show that previous infection with seasonal H1N1 influenza viruses likely explains the requirement for only a single dose of pMIV in adults and that vaccination campaigns with the current pandemic influenza vaccines should reduce viral burden and disease severity in humans. PMID:20962210

  13. Ferreting Out the Identity of Gasoline Additives

    EPA Science Inventory

    Chemical dispersing agents for oil spills, hydraulic fracturing fluids for natural-gas production, and chemicals serving as gasoline additives share a common characteristic—for the most part, they are proprietary compounds. In the name of competitive advantage, companies carefull...

  14. Lagged cells in the inferior colliculus of the awake ferret

    PubMed Central

    Shechter, Barak; Marvit, Peter; Depireux, Didier A

    2010-01-01

    Neurons in primary auditory cortex (AI) encode complex features of the spectral content of sound, such as direction selectivity. Recent findings of temporal symmetry in AI predict a specific organization of the subcortical input into cortex that contributes to the emergence of direction selectivity. We demonstrate two sub-populations of neurons in the central nucleus of the inferior colliculus, which differ in their steady-state temporal response profile: lagged and non-lagged. The lagged cells (23%) are shifted in temporal phase with respect to non-lagged cells and are characterized by an “inhibition first” and delayed excitation in their spectro-temporal receptive fields. Non-lagged cells (77%) have a canonical “excitation first” response. However, we find no difference in the response onset latency to pure tone stimuli between the two sub-populations. Given the homogeneity of tonal response latency, we predict that these lagged cells receive inhibitory input mediated by cortical feedback projections. PMID:20092554

  15. Histamine modulates thalamocortical activity by activating a chloride conductance in ferret perigeniculate neurons.

    PubMed

    Lee, Kendall H; Broberger, Christian; Kim, Uhnoh; McCormick, David A

    2004-04-27

    In the mammalian central nervous system only gamma-aminobutyric acid (GABA) and glycine have been firmly linked to inhibition of neuronal activity through increases in membrane Cl(-) conductance, and these responses are mediated by ionotropic receptors. Iontophoretic application of histamine can also cause inhibitory responses in vivo, although the mechanisms of this inhibition are unknown and may involve pre- or postsynaptic factors. Here, we report that application of histamine to the GABAergic neurons of the thalamic perigeniculate nucleus (PGN), which is innervated by histaminergic fibers from the tuberomammillary nucleus of the hypothalamus, causes a slow membrane hyperpolarization toward a reversal potential of -73 mV through a relatively small increase in membrane conductance to Cl(-). This histaminergic action appears to be mediated by the H(2) subclass of histaminergic receptors and inhibits the single-spike activity of these PGN GABAergic neurons. Application of histamine to the PGN could halt the generation of spindle waves, indicating that increased activity in the tuberomammillary histaminergic system may play a functional role in dampening thalamic oscillations in the transition from sleep to arousal.

  16. Oscillatory Dynamics in the Frontoparietal Attention Network during Sustained Attention in the Ferret.

    PubMed

    Sellers, Kristin K; Yu, Chunxiu; Zhou, Zhe Charles; Stitt, Iain; Li, Yuhui; Radtke-Schuller, Susanne; Alagapan, Sankaraleengam; Fröhlich, Flavio

    2016-09-13

    Sustained attention requires the coordination of neural activity across multiple cortical areas in the frontoparietal network, in particular the prefrontal cortex (PFC) and posterior parietal cortex (PPC). Previous work has demonstrated that activity in these brain regions is coordinated by neuronal oscillations of the local field potential (LFP). However, the underlying coordination of activity in terms of organization of single unit (SU) spiking activity has remained poorly understood, particularly in the freely moving animal. We found that long-range functional connectivity between anatomically connected PFC and PPC was mediated by oscillations in the theta frequency band. SU activity in PFC was phase locked to theta oscillations in PPC, and spiking activity in PFC and PPC was locked to local high-gamma activity. Together, our results support a model in which frequency-specific synchronization mediates functional connectivity between and within PFC and PPC of the frontoparietal attention network in the freely moving animal. PMID:27626658

  17. Oscillatory Dynamics in the Frontoparietal Attention Network during Sustained Attention in the Ferret.

    PubMed

    Sellers, Kristin K; Yu, Chunxiu; Zhou, Zhe Charles; Stitt, Iain; Li, Yuhui; Radtke-Schuller, Susanne; Alagapan, Sankaraleengam; Fröhlich, Flavio

    2016-09-13

    Sustained attention requires the coordination of neural activity across multiple cortical areas in the frontoparietal network, in particular the prefrontal cortex (PFC) and posterior parietal cortex (PPC). Previous work has demonstrated that activity in these brain regions is coordinated by neuronal oscillations of the local field potential (LFP). However, the underlying coordination of activity in terms of organization of single unit (SU) spiking activity has remained poorly understood, particularly in the freely moving animal. We found that long-range functional connectivity between anatomically connected PFC and PPC was mediated by oscillations in the theta frequency band. SU activity in PFC was phase locked to theta oscillations in PPC, and spiking activity in PFC and PPC was locked to local high-gamma activity. Together, our results support a model in which frequency-specific synchronization mediates functional connectivity between and within PFC and PPC of the frontoparietal attention network in the freely moving animal.

  18. Influenza virus respiratory infection and transmission following ocular inoculation in ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of e...

  19. Seasonal trivalent inactivated influenza vaccine protects against 1918 Spanish influenza virus in ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The influenza H1N1 pandemic of 1918 was one of the worst medical disasters in human history. Recent studies have demonstrated that the hemagglutinin (HA) protein of the 1918 virus and 2009 H1N1 pandemic virus, the latter now a component of the seasonal trivalent inactivated influenza vaccine (TIV),...

  20. Small Mammals: Common Surgical Procedures of Rodents, Ferrets, Hedgehogs, and Sugar Gliders.

    PubMed

    Miwa, Yasutsugu; Sladky, Kurt K

    2016-01-01

    Small mammal surgical procedures are a part of clinical veterinary practice and are performed with regularity. Anesthetic and analgesic techniques are important components of any successful small mammal surgical procedure. Many basic surgical principles used in dogs and cats can be directly applied to small mammals, but tissues tend to be smaller and thinner, and hemostasis is critical with small patients due to risk of death with minimal blood loss. Common surgical procedures in small mammals include integumentary mass and abscess excision, reproductive procedures, gastrointestinal foreign body removal, urolith removal, prolapsed tissues associated with the gastrointestinal tract, intra-abdominal mass excision, and hepatic surgery. PMID:26611930

  1. Beta-Cryptoxanthin supplementation prevents cigarette smoke-induced lung inflammation, oxidative damage and squamous metaplasia in ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In epidemiologic studies, high intake of beta-cryptoxanthin has been associated with a decreased risk of lung cancer, particularly among current smokers. However, data are not available from well-controlled animal studies to examine the effects of beta-cryptoxanthin on cigarette smoke-induced lung ...

  2. Dynamics of Phase-Independent Spectro-Temporal Tuning in Primary Auditory Cortex of the Awake Ferret

    PubMed Central

    Depireux, D.A.; Dobbins, H.D.; Marvit, P.; Shechter, B.

    2012-01-01

    Tuning of cortical neurons is often measured as a static property, or during a steady-state regime, despite a number of studies suggesting that tuning depends on when it is meaured during a neuron’s response (e.g., onset vs. sustained vs. offset). We have previously shown that phase-locked tuning to feature transients evolves as a dynamic quantity from the onset of the sound. In this follow-up study, we examined the phase-indepenent tuning during feature transients. Based on previous results, we hypothesized phase-independent tuning should evolve on the same timescale as phase-locked tuning. We used stimuli of constant level, but alternating between flat spectro-temporal envelope and a modulated envelope with well defined spectral density and temporal periodicity This allowed the measure of changes in tuning to novel spectro-temporal content, as happens during running speech and other sounds with rapid transitions without a confounding change in sound level. For 95% of neurons, tuning changed significantly from the onset, over the course of the response. For a majority of these cells, the change occurred within the first 40 ms following a feature onset, often even around 10–20ms. This solidifies the idea that tuning can change rapidly from onset tuning to the sustained, steady-state tuning. PMID:22531376

  3. 78 FR 77485 - Endangered and Threatened Wildlife and Plants; Revised Recovery Plan for the Black-Footed Ferret

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-23

    ... recovery plan available for public comment and peer review from April 23, 2013, to June 24, 2013 (78 FR... North America wherever prairie dogs occurred. The species was listed as endangered in 1967 (32 FR 4001... Endangered Species Conservation Act of 1969 (35 FR 8491, June 2, 1970). On January 4, 1974, the...

  4. Stability of Spectro-Temporal Tuning over Several Seconds in Primary Auditory Cortex of the Awake Ferret

    PubMed Central

    B., Shechter; D.A., Depireux

    2007-01-01

    The steady-state spectro-temporal tuning of auditory cortical cells has been studied using a variety of broad-band stimuli that characterize neurons by their steady-state responses to long duration stimuli, lasting from about a second to several minutes. Central sensory stations are thought to adapt in their response to stimuli presented over extended periods of time. For instance, we have previously shown that auditory cortical neurons display a second order of adaptation, whereby the rate of their adaptation to the repeated presentation of fixed alternating stimuli decreases with each presentation. The auditory grating (or ripple) method of characterizing central auditory neurons, and its extensions, have proven very effective. But these stimuli are typically used with spectro-temporal content held fixed over time-scales of seconds, introducing the possibility of rapid adaptation while the receptive field is being measured, whereas the neural response used to compute a spectro-temporal receptive field (STRF) assumes stationarity in the neural input/output function. We demonstrate dynamic changes in some parameters during the measurement of the STRF over a period of seconds, even absent of a relevant behavioral task. Specifically, we find small but systematic changes in duration and breadth of tuning of STRFs when comparing the early (0.25 sec - 1.75 sec) and late (4.5 sec - 6 sec) segments of the responses to these stimuli. PMID:17693032

  5. A live attenuated cold adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The appearance of human infections caused by avian influenza A H7 subtype viruses underscore their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of ...

  6. Enzymatic formation of apo-carotenoids from the xanthophyll carotenoids lutein, zeaxanthin and b-cryptoxanthin by ferret carotene-9, 10-monooxygenase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Xanthophyll carotenoids, such as lutein, zeaxanthin and b-cryptoxanthin, may provide potential health benefits against chronic and degenerative diseases. Investigating pathways of xanthophyll metabolism are important to understanding their biological functions. Carotene-15,150-monooxygenase (CMO1) h...

  7. Experimental adaptation of an influenza H5HA strain confers respiratory droplet transmission to reassortant H5H/H1N1 virus strain in ferrets.

    PubMed

    Pasternak, Jacyr

    2012-01-01

    An evaluation of the role - if any - of censorship in scientific papers, based on the publishing of the article that shows it is possible to modify the genetics of the H5N1 aviary influenza virus, enhancing its transmission among mammals, which was followed by much ado and ethical discussion. PMID:23386026

  8. A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets and monkeys

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of HP A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (...

  9. Tobacco carcinogen (NNK) induces both lung cancer and non-alcoholic steatohepatitis and hepatocellular carcinomas in ferrets which can be attenuated by lycopene supplementation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early epidemiologic studies have reported that tobacco smoking, which is causally associated with liver cancer, is an independent risk factor for non-alcoholic fatty liver diseases (NAFLD). Lycopene from tomatoes has been shown to be a potential preventive agent against NAFLD and hepatocellular carc...

  10. Pathogenesis of H5N1 influenza virus infections in mice and ferret models differ between respiratory and digestive system exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background. Epidemiological, clinical and laboratory data suggests H5N1 influenza viruses are transmitted through and predominantly affect the respiratory system of mammals. Some data suggests digestive system involvement. However, direct evidence of alimentary transmission and infection in mammal...

  11. Spatial interactions between sympatric carnivores: asymmetric avoidance of an intraguild predator.

    PubMed

    Grassel, Shaun M; Rachlow, Janet L; Williams, Christopher J

    2015-07-01

    Interactions between intraguild species that act as both competitors and predator-prey can be especially complex. We studied patterns of space use by the black-footed ferret (Mustela nigripes), a prairie dog (Cynomys spp.) specialist, and the American badger (Taxidea taxus), a larger generalist carnivore that competes for prairie dogs and is known to kill ferrets. We expected that ferrets would spatially avoid badgers because of the risk of predation, that these patterns of avoidance might differ between sexes and age classes, and that the availability of food and space might influence these relationships. We used location data from 60 ferrets and 15 badgers to model the influence of extrinsic factors (prairie dog density and colony size) and intrinsic factors (sex, age) on patterns of space use by ferrets in relation to space use by different sex and age categories of badgers. We documented asymmetric patterns of avoidance of badgers by ferrets based on the sex of both species. Female ferrets avoided adult female badgers, but not male badgers, and male ferrets exhibited less avoidance than female ferrets. Additionally, avoidance decreased with increasing densities of prairie dogs. We suggest that intersexual differences in space use by badgers create varying distributions of predation risk that are perceived by the smaller carnivore (ferrets) and that females respond more sensitively than males to that risk. This work advances understanding about how competing species coexist and suggests that including information on both intrinsic and extrinsic factors might improve our understanding of behavioral interactions between sympatric species. PMID:26306165

  12. Spatial interactions between sympatric carnivores: asymmetric avoidance of an intraguild predator.

    PubMed

    Grassel, Shaun M; Rachlow, Janet L; Williams, Christopher J

    2015-07-01

    Interactions between intraguild species that act as both competitors and predator-prey can be especially complex. We studied patterns of space use by the black-footed ferret (Mustela nigripes), a prairie dog (Cynomys spp.) specialist, and the American badger (Taxidea taxus), a larger generalist carnivore that competes for prairie dogs and is known to kill ferrets. We expected that ferrets would spatially avoid badgers because of the risk of predation, that these patterns of avoidance might differ between sexes and age classes, and that the availability of food and space might influence these relationships. We used location data from 60 ferrets and 15 badgers to model the influence of extrinsic factors (prairie dog density and colony size) and intrinsic factors (sex, age) on patterns of space use by ferrets in relation to space use by different sex and age categories of badgers. We documented asymmetric patterns of avoidance of badgers by ferrets based on the sex of both species. Female ferrets avoided adult female badgers, but not male badgers, and male ferrets exhibited less avoidance than female ferrets. Additionally, avoidance decreased with increasing densities of prairie dogs. We suggest that intersexual differences in space use by badgers create varying distributions of predation risk that are perceived by the smaller carnivore (ferrets) and that females respond more sensitively than males to that risk. This work advances understanding about how competing species coexist and suggests that including information on both intrinsic and extrinsic factors might improve our understanding of behavioral interactions between sympatric species.

  13. Spatial interactions between sympatric carnivores: asymmetric avoidance of an intraguild predator

    PubMed Central

    Grassel, Shaun M; Rachlow, Janet L; Williams, Christopher J

    2015-01-01

    Interactions between intraguild species that act as both competitors and predator–prey can be especially complex. We studied patterns of space use by the black-footed ferret (Mustela nigripes), a prairie dog (Cynomys spp.) specialist, and the American badger (Taxidea taxus), a larger generalist carnivore that competes for prairie dogs and is known to kill ferrets. We expected that ferrets would spatially avoid badgers because of the risk of predation, that these patterns of avoidance might differ between sexes and age classes, and that the availability of food and space might influence these relationships. We used location data from 60 ferrets and 15 badgers to model the influence of extrinsic factors (prairie dog density and colony size) and intrinsic factors (sex, age) on patterns of space use by ferrets in relation to space use by different sex and age categories of badgers. We documented asymmetric patterns of avoidance of badgers by ferrets based on the sex of both species. Female ferrets avoided adult female badgers, but not male badgers, and male ferrets exhibited less avoidance than female ferrets. Additionally, avoidance decreased with increasing densities of prairie dogs. We suggest that intersexual differences in space use by badgers create varying distributions of predation risk that are perceived by the smaller carnivore (ferrets) and that females respond more sensitively than males to that risk. This work advances understanding about how competing species coexist and suggests that including information on both intrinsic and extrinsic factors might improve our understanding of behavioral interactions between sympatric species. PMID:26306165

  14. The effect of combined antioxidant supplementation (beta-carotene, ascorbic acid and alpha-tocopherol) on the expression of CMO1 and CMO2 in smoke-exposed ferrets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Contrary to the results of observational studies showing a beneficial effect of increased intakes of fruits and vegetables high in beta-carotene (BC) on lung cancer, intervention trials using high dose BC supplements in heavy smokers demonstrated either a harmful or no effect of BC on the relative r...

  15. Etologia aplicada al manejo de especies amenazadas: el caso del turon de patas negras (Mustela nigripes)

    USGS Publications Warehouse

    Vargas, A.; Biggins, D.; Miller, B.

    1999-01-01

    de esta especie de un modo más eficaz y rentable. Black-footed ferrets are considered one of the world's most endangered mammals. The last wild population was discovered in 1981 in Meteetsee, Wyoming, and, in 1985 it collapsed due to an epizootic of canine distemper in combination with sylvatic plague. Prior to the extinction of the last remnant population, 18 wild black-footed ferrets were captured to initiate captive propagation efforts. Captive breeding has been successful and, during the last 11 years, more than 2600 black-footed ferrets have been born in captive breeding centers. Since 1991, approximately 870 ferrets have been reintroduced in 5 areas located within the ferret's original geographic distribution, including sites in Wyoming, Montana, South Dakota, and Arizona. Scientific research has been, and continues to be, a critical tool to direct recovery efforts. Studies in applied ethology conducted on captive and reintroduced ferret populations have demonstrated that a naturalistic captive environment, particularly during early developmental periods, enhances the expression of behaviors necessary for survival in nature. Ferrets raised in a naturalistic environment develop better predatory skills, are able to recognize prairie dog burrows as a home and shelter from predators, and are more physically fit. Results from these studies have been adapted into management strategies to help implement a more cost-effective road to black-footed ferret recovery.

  16. Adenosine Deaminase Acts as a Natural Antagonist for Dipeptidyl Peptidase 4-Mediated Entry of the Middle East Respiratory Syndrome Coronavirus

    PubMed Central

    Raj, V. Stalin; Smits, Saskia L.; Provacia, Lisette B.; van den Brand, Judith M. A.; Wiersma, Lidewij; Ouwendijk, Werner J. D.; Bestebroer, Theo M.; Spronken, Monique I.; van Amerongen, Geert; Rottier, Peter J. M.; Fouchier, Ron A. M.; Bosch, Berend Jan; Osterhaus, Albert D.M.E.

    2014-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) replicates in cells of different species using dipeptidyl peptidase 4 (DPP4) as a functional receptor. Here we show the resistance of ferrets to MERS-CoV infection and inability of ferret DDP4 to bind MERS-CoV. Site-directed mutagenesis of amino acids variable in ferret DPP4 thus revealed the functional human DPP4 virus binding site. Adenosine deaminase (ADA), a DPP4 binding protein, competed for virus binding, acting as a natural antagonist for MERS-CoV infection. PMID:24257613

  17. Adenosine deaminase acts as a natural antagonist for dipeptidyl peptidase 4-mediated entry of the Middle East respiratory syndrome coronavirus.

    PubMed

    Raj, V Stalin; Smits, Saskia L; Provacia, Lisette B; van den Brand, Judith M A; Wiersma, Lidewij; Ouwendijk, Werner J D; Bestebroer, Theo M; Spronken, Monique I; van Amerongen, Geert; Rottier, Peter J M; Fouchier, Ron A M; Bosch, Berend Jan; Osterhaus, Albert D M E; Haagmans, Bart L

    2014-02-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) replicates in cells of different species using dipeptidyl peptidase 4 (DPP4) as a functional receptor. Here we show the resistance of ferrets to MERS-CoV infection and inability of ferret DDP4 to bind MERS-CoV. Site-directed mutagenesis of amino acids variable in ferret DPP4 thus revealed the functional human DPP4 virus binding site. Adenosine deaminase (ADA), a DPP4 binding protein, competed for virus binding, acting as a natural antagonist for MERS-CoV infection. PMID:24257613

  18. What Is the Rabies Risk for My Pet?

    MedlinePlus

    ... as having been exposed to rabies. Unvaccinated dogs, cats, and ferrets exposed to a rabid animal should ... on a case-by-case basis. Dogs and cats that are currently vaccinated are kept under observation ...

  19. Rabies: Diagnosis in Animals and Humans

    MedlinePlus

    ... a low probability of rabies such as dogs, cats, and ferrets, observation periods (10 days) may be ... 2008 Rabies in Domestic Animals, 1958-2008 Rabid Cats Reported in the United States, 2008 Rabid Dogs ...

  20. Rabies: Questions and Answers

    MedlinePlus

    ... my child? Rabies is not common in dogs, cats, ferrets, and live- stock in the United States ... rabies isn't common in U.S. dogs and cats anymore, is there anything to worry about? Unfortunately, ...

  1. 78 FR 71623 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ... July 2, 2013 (78 FR 39734), FDA published a 60-day notice requesting public comment on the proposed..., parrots, ferrets, and guinea pigs. Some animals of agricultural importance are also minor species....

  2. 75 FR 59721 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... pharmaceutical companies that sponsor new animal drugs. In the Federal Register of July 20, 2010 (75 FR 42094... the major species, for example, zoo animals, ornamental fish, parrots, ferrets, and guinea pigs....

  3. [Reproductive physiology of the European mink: progesterone profile during pregnancy].

    PubMed

    Amstislavskiĭ, S Ia; Zav'ialov, E L; Ternovskaia, Iu G; Gerlinskaia, L A

    2010-04-01

    Reproductive physiology of the European mink, an endangered mustelid species, has been so far scarcely investigated. This study confirms that in European mink embryo implantation occurs on the day 12 of pregnancy. Progesterone profile during pregnancy has been compared in European mink and domestic ferret. In both species, progesterone increases at peri-implantation period, i. e. on day 8 and day 12 after mating. However, toward the end of pregnancy, on day 40 after mating, progesterone concentration in faeces of the ferrets decreases and does not differ from the initial level. In contrast, increase of progesterone during first 12 days of pregnancy in European mink is not as rapid as in ferrets, but in this species, there is no visible decrease of progesterone at the end of pregnancy. Peak levels of progesterone in faeces (day 8, 12) are lower in European mink than in ferret.

  4. Ringworm

    MedlinePlus

    ... Cats Dogs Farm Animals Backyard Poultry Ferrets Fish Horses Reptiles and Amphibians Turtles Kept as Pets Small ... Everyone is Equal On the Back of a Horse Chickens in the City Diseases Cat-scratch disease ( ...

  5. Antigenic Maps of Influenza A(H3N2) Produced With Human Antisera Obtained After Primary Infection

    PubMed Central

    Fonville, Judith M.; Fraaij, Pieter L. A.; de Mutsert, Gerrie; Wilks, Samuel H.; van Beek, Ruud; Fouchier, Ron A. M.; Rimmelzwaan, Guus F.

    2016-01-01

    Background Antigenic characterization of influenza viruses is typically based on hemagglutination inhibition (HI) assay data for viral isolates tested against strain-specific postinfection ferret antisera. Here, similar virus characterizations were performed using serological data from humans with primary influenza A(H3N2) infection. Methods We screened sera collected between 1995 and 2011 from children between 9 and 24 months of age for influenza virus antibodies, performed HI tests for the positive sera against 23 influenza viruses isolated between 1989 and 2011, and measured HI titers of antisera against influenza A(H3N2) from 24 ferrets against the same panel of viruses. Results Of the 17 positive human sera, 6 had a high response, showing HI patterns that would be expected from primary infection antisera, while 11 sera had lower, more dispersed patterns of reactivity that are not easily explained. The antigenic map based on the high-response human HI data was similar to the map created using ferret data. Conclusions Although the overall structure of the ferret and human antigenic maps is similar, local differences in virus positions indicate that the human and ferret immune system might see antigenic properties of viruses differently. Further studies are needed to establish the degree of similarity between serological patterns in ferret and human data. PMID:26142433

  6. Pathogenesis and transmission of triple-reassortant swine H1N1 influenza viruses isolated before the 2009 H1N1 pandemic.

    PubMed

    Belser, Jessica A; Gustin, Kortney M; Maines, Taronna R; Blau, Dianna M; Zaki, Sherif R; Katz, Jacqueline M; Tumpey, Terrence M

    2011-02-01

    The 2009 H1N1 pandemic influenza virus represents the greatest incidence of human infection with an influenza virus of swine origin to date. Moreover, triple-reassortant swine (TRS) H1N1 viruses, which share similar host and lineage origins with 2009 H1N1 viruses, have been responsible for sporadic human cases since 2005. Similar to 2009 H1N1 viruses, TRS viruses are capable of causing severe disease in previously healthy individuals and frequently manifest with gastrointestinal symptoms; however, their ability to cause severe disease has not been extensively studied. Here, we evaluated the pathogenicity and transmissibility of two TRS viruses associated with disease in humans in the ferret model. TRS and 2009 H1N1 viruses exhibited comparable viral titers and histopathologies following virus infection and were similarly unable to transmit efficiently via respiratory droplets in the ferret model. Utilizing TRS and 2009 H1N1 viruses, we conducted extensive hematologic and blood serum analyses on infected ferrets to identify lymphohematopoietic parameters associated with mild to severe influenza virus infection. Following H1N1 or H5N1 influenza virus infection, ferrets were found to recapitulate several laboratory abnormalities previously documented with human disease, furthering the utility of the ferret model for the assessment of influenza virus pathogenicity.

  7. Transmission Routes for Nipah Virus from Malaysia and Bangladesh

    PubMed Central

    Clayton, Bronwyn A.; Middleton, Deborah; Bergfeld, Jemma; Haining, Jessica; Arkinstall, Rachel; Wang, Linfa

    2012-01-01

    Human infections with Nipah virus in Malaysia and Bangladesh are associated with markedly different patterns of transmission and pathogenicity. To compare the 2 strains, we conducted an in vivo study in which 2 groups of ferrets were oronasally exposed to either the Malaysia or Bangladesh strain of Nipah virus. Viral shedding and tissue tropism were compared between the 2 groups. Over the course of infection, significantly higher levels of viral RNA were recovered from oral secretions of ferrets infected with the Bangladesh strain. Higher levels of oral shedding of the Bangladesh strain of Nipah virus might be a key factor in onward transmission in outbreaks among humans. PMID:23171621

  8. Growth and Pathogenic Potential of Naturally Selected Reassortants after Coinfection with Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Viruses

    PubMed Central

    Song, Min-Suk; Baek, Yun Hee; Pascua, Philippe Noriel Q.; Kwon, Hyeok-il; Kim, Eun-Ha; Park, Su-Jin; Kim, Se Mi; Kim, Young-Il; Choi, Won-Suk; Kim, Eung-Gook; Kim, Chul-Joong

    2015-01-01

    Coinfection of ferrets with H5N1 and pH1N1 viruses resulted in two predominate genotypes in the lungs containing surface genes of highly pathogenic avian influenza H5N1 virus in the backbone of pandemic H1N1 2009 (pH1N1). Compared to parental strains, these reassortants exhibited increased growth and virulence in vitro and in mice but failed to be transmitted indirectly to naive contact ferrets. Thus, this demonstrates a possible natural reassortment following coinfection as well as the pathogenicity of the potential reassortants. PMID:26491154

  9. Growth and Pathogenic Potential of Naturally Selected Reassortants after Coinfection with Pandemic H1N1 and Highly Pathogenic Avian Influenza H5N1 Viruses.

    PubMed

    Song, Min-Suk; Baek, Yun Hee; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Kim, Eun-Ha; Park, Su-Jin; Kim, Se Mi; Kim, Young-Il; Choi, Won-Suk; Kim, Eung-Gook; Kim, Chul-Joong; Choi, Young Ki

    2016-01-01

    Coinfection of ferrets with H5N1 and pH1N1 viruses resulted in two predominate genotypes in the lungs containing surface genes of highly pathogenic avian influenza H5N1 virus in the backbone of pandemic H1N1 2009 (pH1N1). Compared to parental strains, these reassortants exhibited increased growth and virulence in vitro and in mice but failed to be transmitted indirectly to naive contact ferrets. Thus, this demonstrates a possible natural reassortment following coinfection as well as the pathogenicity of the potential reassortants. PMID:26491154

  10. Canine Distemper Virus Epithelial Cell Infection Is Required for Clinical Disease but Not for Immunosuppression

    PubMed Central

    Sawatsky, Bevan; Wong, Xiao-Xiang; Hinkelmann, Sarah; Cattaneo, Roberto

    2012-01-01

    To characterize the importance of infection of epithelial cells for morbillivirus pathogenesis, we took advantage of the severe disease caused by canine distemper virus (CDV) in ferrets. To obtain a CDV that was unable to enter epithelial cells but retained the ability to enter immune cells, we transferred to its attachment (H) protein two mutations shown to interfere with the interaction of measles virus H with its epithelial receptor, human nectin-4. As expected for an epithelial receptor (EpR)-blind CDV, this virus infected dog and ferret epithelial cells inefficiently and did not cause cell fusion or syncytium formation. On the other hand, the EpR-blind CDV replicated in cells expressing canine signaling lymphocyte activation molecule (SLAM), the morbillivirus immune cell receptor, with similar kinetics to those of wild-type CDV. While ferrets infected with wild-type CDV died within 12 days after infection, after developing severe rash and fever, animals infected with the EpR-blind virus showed no clinical signs of disease. Nevertheless, both viruses spread rapidly and efficiently in immune cells, causing similar levels of leukopenia and inhibition of lymphocyte proliferation activity, two indicators of morbillivirus immunosuppression. Infection was documented for airway epithelia of ferrets infected with wild-type CDV but not for those of animals infected with the EpR-blind virus, and only animals infected with wild-type CDV shed virus. Thus, epithelial cell infection is necessary for clinical disease and efficient virus shedding but not for immunosuppression. PMID:22278252

  11. Internet Search Engines - Fluctuations in Document Accessibility.

    ERIC Educational Resources Information Center

    Mettrop, Wouter; Nieuwenhuysen, Paul

    2001-01-01

    Reports an empirical investigation of the consistency of retrieval through Internet search engines. Evaluates 13 engines: AltaVista, EuroFerret, Excite, HotBot, InfoSeek, Lycos, MSN, NorthernLight, Snap, WebCrawler, and three national Dutch engines: Ilse, Search.nl and Vindex. The focus is on a characteristic related to size: the degree of…

  12. Replication Capacity of Avian Influenza A(H9N2) Virus in Pet Birds and Mammals, Bangladesh.

    PubMed

    Lenny, Brian J; Shanmuganatham, Karthik; Sonnberg, Stephanie; Feeroz, Mohammed M; Alam, S M Rabiul; Hasan, M Kamrul; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webster, Robert G; Jones, Jeremy C

    2015-12-01

    Avian influenza A(H9N2) is an agricultural and public health threat. We characterized an H9N2 virus from a pet market in Bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. Results implicated pet birds in the potential dissemination and zoonotic transmission of this virus.

  13. National Audubon Society Specials. Teacher's Guide I.

    ERIC Educational Resources Information Center

    WETA - TV, Washington, DC.

    Since no civilization can survive without a healthy environment, people must learn to live in harmony with their natural ecosystems and build for future generations. This guide describes six award-winning programs on the condor, black-footed ferret, panthers and cheetahs, ducks, farming and wildlife, and the Galapagos Islands. Although each…

  14. 9 CFR 2.1 - Requirements and application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... animals, such as dogs, cats, birds, rabbits, hamsters, guinea pigs, gophers, domestic ferrets, chinchilla... animals, dogs, or cats, and who derives no more than $500 gross income from the sale of such animals to a... dogs, cats, and/or small exotic or wild mammals, such as hedgehogs, degus, spiny mice, prairie...

  15. 9 CFR 2.1 - Requirements and application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... animals, such as dogs, cats, birds, rabbits, hamsters, guinea pigs, gophers, domestic ferrets, chinchilla... animals, dogs, or cats, and who derives no more than $500 gross income from the sale of such animals to a... dogs, cats, and/or small exotic or wild mammals, such as hedgehogs, degus, spiny mice, prairie...

  16. Spatial Temporal Dynamics and Molecular Evolution of Re-Emerging Rabies Virus in Taiwan.

    PubMed

    Lin, Yung-Cheng; Chu, Pei-Yu; Chang, Mei-Yin; Hsiao, Kuang-Liang; Lin, Jih-Hui; Liu, Hsin-Fu

    2016-03-17

    Taiwan has been recognized by the World Organization for Animal Health as rabies-free since 1961. Surprisingly, rabies virus (RABV) was identified in a dead Formosan ferret badger in July 2013. Later, more infected ferret badgers were reported from different geographic regions of Taiwan. In order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and Bayesian methods based on the full-length of glycoprotein (G), matrix protein (M), and nucleoprotein (N) genes. The evolutionary rates and phylogeographic were determined using Beast and SPREAD software. Phylogenetic trees showed a monophyletic group containing all of RABV isolates from Taiwan and it further separated into three sub-groups. The estimated nucleotide substitution rates of G, M, and N genes were between 2.49 × 10(-4)-4.75 × 10(-4) substitutions/site/year, and the mean ratio of dN/dS was significantly low. The time of the most recent common ancestor was estimated around 75, 89, and 170 years, respectively. Phylogeographic analysis suggested the origin of the epidemic could be in Eastern Taiwan, then the Formosan ferret badger moved across the Central Range of Taiwan to western regions and separated into two branches. In this study, we illustrated the evolution history and phylogeographic of RABV in Formosan ferret badgers.

  17. Managing prairie dogs by managing plague: a vaccine for the future?

    USGS Publications Warehouse

    Johnson, Terry B.; Rocke, Tonie E.; Gober, Pete; Van Pelt, Bill E.; Miller, Michael W.; Tripp, Daniel W.; Abbott, Rachel C.; Bergman, David L.

    2014-01-01

    The Black-footed Ferret Recovery Implementation Team Executive Committee is conducting a project to develop,and (hopefully) eventually implement, a plague vaccination program for prairie dogs. The project is a component of the WesternAssociation of Fish and Wildlife Agencies Grasslands Conservation Initiative. An effective, field-worthy vaccine against plaguecould be the biggest breakthrough in recovery efforts for the black-footed ferret since the 1981 rediscovery of wild ferrets nearMeeteetse, Wyoming. If proven efficacious, the vaccine could help agencies and stakeholder cooperators maintain specificpopulations of prairie dogs at robust levels, thus enhancing range-wide conservation of those species, as well recovery of the ferret,while enabling control of other prairie dog populations to resolve site-specific agricultural and human health concerns. The resultsof laboratory and field-testing in the early stages of developing this vaccine are preliminary but mostly encouraging. A plan forbroad-scale application is being developed for possible use when testing has been completed and (if warranted) the vaccine isregistered for governmental use. An overview of all aspects of the project is discussed.

  18. Teaching: A Reflective Process

    ERIC Educational Resources Information Center

    German, Susan; O'Day, Elizabeth

    2009-01-01

    In this article, the authors describe how they used formative assessments to ferret out possible misconceptions among middle-school students in a unit about weather-related concepts. Because they teach fifth- and eighth-grade science, this assessment also gives them a chance to see how student understanding develops over the years. This year they…

  19. 77 FR 63783 - Influenza Viruses Containing the Hemagglutinin from the Goose/Guangdong/1/96 Lineage

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... transmissibility of genetically modified H5N1 viruses among ferrets, together with the fact that the level of... independent studies (Ref 9 and Ref 10), investigators have shown that laboratory modified HPAI H5N1 influenza... National Institutes of Health (HHS/NIH), the Food and Drug Administration (HHS/FDA), USDA/APHIS, the...

  20. Nonreplicating Influenza A Virus Vaccines Confer Broad Protection against Lethal Challenge

    PubMed Central

    Baz, Mariana; Boonnak, Kobporn; Paskel, Myeisha; Santos, Celia; Powell, Timothy; Townsend, Alain

    2015-01-01

    ABSTRACT New vaccine technologies are being investigated for their ability to elicit broadly cross-protective immunity against a range of influenza viruses. We compared the efficacies of two intranasally delivered nonreplicating influenza virus vaccines (H1 and H5 S-FLU) that are based on the suppression of the hemagglutinin signal sequence, with the corresponding H1N1 and H5N1 cold-adapted (ca) live attenuated influenza virus vaccines in mice and ferrets. Administration of two doses of H1 or H5 S-FLU vaccines protected mice and ferrets from lethal challenge with homologous, heterologous, and heterosubtypic influenza viruses, and two doses of S-FLU and ca vaccines yielded comparable effects. Importantly, when ferrets immunized with one dose of H1 S-FLU or ca vaccine were challenged with the homologous H1N1 virus, the challenge virus failed to transmit to naive ferrets by the airborne route. S-FLU technology can be rapidly applied to any emerging influenza virus, and the promising preclinical data support further evaluation in humans. PMID:26489862

  1. Spatial Temporal Dynamics and Molecular Evolution of Re-Emerging Rabies Virus in Taiwan.

    PubMed

    Lin, Yung-Cheng; Chu, Pei-Yu; Chang, Mei-Yin; Hsiao, Kuang-Liang; Lin, Jih-Hui; Liu, Hsin-Fu

    2016-01-01

    Taiwan has been recognized by the World Organization for Animal Health as rabies-free since 1961. Surprisingly, rabies virus (RABV) was identified in a dead Formosan ferret badger in July 2013. Later, more infected ferret badgers were reported from different geographic regions of Taiwan. In order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and Bayesian methods based on the full-length of glycoprotein (G), matrix protein (M), and nucleoprotein (N) genes. The evolutionary rates and phylogeographic were determined using Beast and SPREAD software. Phylogenetic trees showed a monophyletic group containing all of RABV isolates from Taiwan and it further separated into three sub-groups. The estimated nucleotide substitution rates of G, M, and N genes were between 2.49 × 10(-4)-4.75 × 10(-4) substitutions/site/year, and the mean ratio of dN/dS was significantly low. The time of the most recent common ancestor was estimated around 75, 89, and 170 years, respectively. Phylogeographic analysis suggested the origin of the epidemic could be in Eastern Taiwan, then the Formosan ferret badger moved across the Central Range of Taiwan to western regions and separated into two branches. In this study, we illustrated the evolution history and phylogeographic of RABV in Formosan ferret badgers. PMID:26999115

  2. Government Response to the Discovery of a Rabies Virus Reservoir Species on a Previously Designated Rabies-Free Island, Taiwan, 1999-2014.

    PubMed

    Chang, S-S; Tsai, H-J; Chang, F-Y; Lee, T-S; Huang, K-C; Fang, K-Y; Wallace, R M; Inoue, S; Fei, C-Y

    2016-08-01

    Taiwan had been considered rabies free since 1961. In 2013, Taiwan confirmed the detection of rabies virus in wild Taiwan ferret-badgers. Up to December 2014, there have been 423 rabies-confirmed ferret-badgers and three cases of spillover infection into non-reservoir hosts. Genetic analysis indicates that TFBV is distinct from all other known rabies virus variants. To date, ferret-badger rabies is known to occur only in China and Taiwan. The temporal dynamics of rabid ferret-badgers in Taiwan suggests that the epizootic appears to have subsided to enzootic levels as of December 2014. According to the current epidemiologic data, there is only one TFBV strain in Taiwan. TFBV is still sequestered to the mountainous regions. Humans are at risk mainly through exposure to the virus from infected domestic meso-carnivores, mainly dogs and cats. Dogs and cats should be vaccinated to establish an immunological barrier to stop the spread of the disease from mountainous regions to domestic meso-carnivores. PMID:26542085

  3. Fecundity of the sea lamprey (Petromyzon marinus) in Lake Superior

    USGS Publications Warehouse

    Manion, Patrick J.

    1972-01-01

    An infectious agent, which appears to be a virus (RJV) has been isolated from the liver of a wild raccoon which has led to a highly fatal type of disease characterized by conjunctivitis and an elevated serum bilirubin frequently accompanied by jaundice on inoculation of raccoons. Ferrets also appear to be susceptible to infections with this agent.

  4. Isolation of an agent causing bilirubinemia and jaundice in raccoons

    USGS Publications Warehouse

    Kilham, L.; Herman, C.M.

    1954-01-01

    An infectious agent, which appears to be a virus (RJV) has been isolated from the liver of a wild raccoon which has led to a highly fatal type of disease characterized by conjunctivitis and an elevated serum bilirubin frequently accompanied by jaundice on inoculation of raccoons. Ferrets also appear to be susceptible to infections with this agent.

  5. Pandemic (H1N1) 2009 in captive cheetah.

    PubMed

    Crossley, Beate; Hietala, Sharon; Hunt, Tania; Benjamin, Glenn; Martinez, Marie; Darnell, Daniel; Rubrum, Adam; Webby, Richard

    2012-02-01

    We describe virus isolation, full genome sequence analysis, and clinical pathology in ferrets experimentally inoculated with pandemic (H1N1) 2009 virus recovered from a clinically ill captive cheetah that had minimal human contact. Evidence of reverse zoonotic transmission by fomites underscores the substantial animal and human health implications of this virus.

  6. Cardiovascular Disease as a Risk Factor for Enhanced Susceptibility to Air Pollutants

    EPA Science Inventory

    Adverse health effects caused by airborne particular matter (PM) are restricted primarily to susceptible populations. The actual risk of anyone individual is quite small, but because of the large number of exposed people, the overall population risk is significant. Ferreting out ...

  7. Our Zoo to You

    ERIC Educational Resources Information Center

    Wickless, Mimi; Brooks, David W.; Abuloum, Amjad; Mancuso, Brian; Heng-Moss, Tiffany M.; Mayo, Lois

    2003-01-01

    An innovative zoo outreach program, Our Zoo to You, places zoo animals in local classrooms for extended observation periods. With guidance and support from zoo staff, students are able to safely experience a variety of animals, including geckos, snakes, legless lizards, horned toads, ringneck doves, ferrets, hedgehogs, African brown millipedes,…

  8. Replication Capacity of Avian Influenza A(H9N2) Virus in Pet Birds and Mammals, Bangladesh

    PubMed Central

    Lenny, Brian J.; Shanmuganatham, Karthik; Sonnberg, Stephanie; Feeroz, Mohammed M.; Alam, S.M. Rabiul; Hasan, M. Kamrul; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webster, Robert G.

    2015-01-01

    Avian influenza A(H9N2) is an agricultural and public health threat. We characterized an H9N2 virus from a pet market in Bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. Results implicated pet birds in the potential dissemination and zoonotic transmission of this virus. PMID:26583371

  9. Replication Capacity of Avian Influenza A(H9N2) Virus in Pet Birds and Mammals, Bangladesh.

    PubMed

    Lenny, Brian J; Shanmuganatham, Karthik; Sonnberg, Stephanie; Feeroz, Mohammed M; Alam, S M Rabiul; Hasan, M Kamrul; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webster, Robert G; Jones, Jeremy C

    2015-12-01

    Avian influenza A(H9N2) is an agricultural and public health threat. We characterized an H9N2 virus from a pet market in Bangladesh and demonstrated replication in samples from pet birds, swine tissues, human airway and ocular cells, and ferrets. Results implicated pet birds in the potential dissemination and zoonotic transmission of this virus. PMID:26583371

  10. Spatial Temporal Dynamics and Molecular Evolution of Re-Emerging Rabies Virus in Taiwan

    PubMed Central

    Lin, Yung-Cheng; Chu, Pei-Yu; Chang, Mei-Yin; Hsiao, Kuang-Liang; Lin, Jih-Hui; Liu, Hsin-Fu

    2016-01-01

    Taiwan has been recognized by the World Organization for Animal Health as rabies-free since 1961. Surprisingly, rabies virus (RABV) was identified in a dead Formosan ferret badger in July 2013. Later, more infected ferret badgers were reported from different geographic regions of Taiwan. In order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and Bayesian methods based on the full-length of glycoprotein (G), matrix protein (M), and nucleoprotein (N) genes. The evolutionary rates and phylogeographic were determined using Beast and SPREAD software. Phylogenetic trees showed a monophyletic group containing all of RABV isolates from Taiwan and it further separated into three sub-groups. The estimated nucleotide substitution rates of G, M, and N genes were between 2.49 × 10−4–4.75 × 10−4 substitutions/site/year, and the mean ratio of dN/dS was significantly low. The time of the most recent common ancestor was estimated around 75, 89, and 170 years, respectively. Phylogeographic analysis suggested the origin of the epidemic could be in Eastern Taiwan, then the Formosan ferret badger moved across the Central Range of Taiwan to western regions and separated into two branches. In this study, we illustrated the evolution history and phylogeographic of RABV in Formosan ferret badgers. PMID:26999115

  11. 78 FR 4866 - Endangered and Threatened Wildlife and Plants; Enhancement of Survival Permit Application; Draft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-23

    ... availability; reopening of comment period. SUMMARY: We, the U.S. Fish and Wildlife Service (Service), are.... ADDRESSES: Send comments by U.S. mail to Kimberly Tamkun, U.S. Fish and Wildlife Service, National Black...: Pete Gober, Black-footed Ferret Recovery ] Coordinator, U.S. Fish and Wildlife Service, (970)...

  12. Replication and transmission of mammalian-adapted H9 subtype influenza virus in pigs and quail

    PubMed Central

    Obadan, Adebimpe O.; Kimble, Brian J.; Rajao, Daniela; Lager, Kelly; Santos, Jefferson J. S.; Vincent, Amy

    2015-01-01

    Influenza A virus is a major pathogen of birds, swine and humans. Strains can jump between species in a process often requiring mutations and reassortment, resulting in outbreaks and, potentially, pandemics. H9N2 avian influenza is predominant in poultry across Asia and occasionally infects humans and swine. Pandemic H1N1 (H1N1pdm) is endemic in humans and swine and has a history of reassortment in pigs. Previous studies have shown the compatibility of H9N2 and H1N1pdm for reassortment in ferrets, a model for human infection and transmission. Here, the effects of ferret adaptation of H9 surface gene segments on the infectivity and transmission in at-risk natural hosts, specifically swine and quail, were analysed. Reassortant H9N1 and H9N2 viruses, carrying seven or six gene segments from H1N1pdm, showed infectivity and transmissibility in swine, unlike the wholly avian H9N2 virus with ferret-adapted surface genes. In quail, only the reassortant H9N2 with the six internal gene segments from the H1N1pdm strain was able to infect and transmit, although less efficiently than the wholly avian H9N2 virus with ferret-adapted surface genes. These results highlight that ferret-adapted mutations on the haemagglutinin of H9 subtype virus do not restrict the ability of the virus to infect swine and quail, and that the ability to transmit in these species depends on the context of the whole virus. As such, this study emphasizes the threat that H9N2 reassortant viruses pose to humans and agricultural species and the importance of the genetic constellation of the virus to its ability to replicate and transmit in natural hosts of influenza. PMID:25986634

  13. Cranial variation in British mustelids.

    PubMed

    Lee, S; Mill, P J

    2004-04-01

    Nineteen measurements were made on 136 skulls belonging to seven mustelid species: Meles meles (Eurasian badger), Mustela nivalis, (weasel), Mustela erminea (stoat), Mustela putorius (polecat), Lutra lutra (otter), Mustela furo (ferret), and Mustela vison (American mink), and polecat-ferret hybrids. To investigate shape, size-related effects were eliminated by dividing all measurements by their geometric means. Canonical variate analysis was used to reveal major interspecies distinctions. Excluding the ferrets and polecat-ferrets from the analysis, only 3.2% of the skulls misclassified (one mink, one weasel, and two stoats). Three groups separated on the first canonical axis: 1) badgers, 2) polecats, mink, and otters, and 3) stoats and weasels. The important variables were width of zygomatic arch and height of sagittal crest opposed to the postorbital distance, condylobasal length, and basilar length. Otters separated out on the second canonical axis; the most important variables were postorbital breadth and width of the postorbital constriction opposed to the basioccipital width. There was reasonable separation of polecats from mink on a combination of the second and third canonical axes. On the latter the most important variables were postorbital breadth opposed to postorbital distance. Addition of the ferret data showed that they lay closest to, and overlapped with, the polecats. The stoat and weasel data alone gave complete separation, with height of sagittal crest and width of zygomatic arch opposed to basioccipital width. However, using size-in data the best separation was the relationship between postorbital breadth and either basioccipital width or postorbital distance. Sexual dimorphism was demonstrated in the skulls of badgers but was shown to be relatively insignificant when compared to the interspecific differences. PMID:15052596

  14. The broad-spectrum anti-emetic activity of the novel non-peptide tachykinin NK1 receptor antagonist GR203040.

    PubMed Central

    Gardner, C. J.; Twissell, D. J.; Dale, T. J.; Gale, J. D.; Jordan, C. C.; Kilpatrick, G. J.; Bountra, C.; Ward, P.

    1995-01-01

    1. Following our earlier observations that the tachykinin NK1 receptor antagonist CP-99,994 is an effective anti-emetic in ferrets, we have examined the anti-emetic effects of a more potent and novel NK1 receptor antagonist, GR203040, against various emetic stimuli in the ferret, dog and house musk shrew (Suncus murinus). 2. In ferrets, GR203040 (0.1 mg kg-1 s.c. or i.v.) is effective against emesis induced by radiation, cisplatin, cyclophosphamide, copper sulphate, ipecacuanha or morphine. 3. In animals in which emesis had been established with cisplatin, GR203040 (1 mg kg-1 s.c.) was fully effective as an interventional treatment. No further emesis was seen in animals treated with GR203040 whilst saline-treated animals continued to vomit. 4. GR203040 (0.1 mg kg-1 s.c.) retains anti-emetic efficacy in the ferret, even when given as a 6 h pretreatment, indicating that this compound has a long duration of action. The compound is also effective orally at the same dose, when given as a 90 min pretreatment. 5. GR203040 (0.1 mg kg-1 i.v.) is fully effective against ipecacuanha-induced emesis in the dog. 6. GR203040 is effective against motion- and cisplatin-induced emesis in Suncus murinus. These effects were seen at doses an order of magnitude greater than those shown to be effective against cisplatin in the ferret. 7. In conclusion, GR203040 is a novel anti-emetic agent, and the broad spectrum of anti-emetic activity, together with activity observed in three species, suggests that this compound is worthy of clinical investigation. Images Figure 2 Figure 4 PMID:8719790

  15. Building the Ferretome

    PubMed Central

    Sukhinin, Dmitrii I.; Engel, Andreas K.; Manger, Paul; Hilgetag, Claus C.

    2016-01-01

    Databases of structural connections of the mammalian brain, such as CoCoMac (cocomac.g-node.org) or BAMS (https://bams1.org), are valuable resources for the analysis of brain connectivity and the modeling of brain dynamics in species such as the non-human primate or the rodent, and have also contributed to the computational modeling of the human brain. Another animal model that is widely used in electrophysiological or developmental studies is the ferret; however, no systematic compilation of brain connectivity is currently available for this species. Thus, we have started developing a database of anatomical connections and architectonic features of the ferret brain, the Ferret(connect)ome, www.Ferretome.org. The Ferretome database has adapted essential features of the CoCoMac methodology and legacy, such as the CoCoMac data model. This data model was simplified and extended in order to accommodate new data modalities that were not represented previously, such as the cytoarchitecture of brain areas. The Ferretome uses a semantic parcellation of brain regions as well as a logical brain map transformation algorithm (objective relational transformation, ORT). The ORT algorithm was also adopted for the transformation of architecture data. The database is being developed in MySQL and has been populated with literature reports on tract-tracing observations in the ferret brain using a custom-designed web interface that allows efficient and validated simultaneous input and proofreading by multiple curators. The database is equipped with a non-specialist web interface. This interface can be extended to produce connectivity matrices in several formats, including a graphical representation superimposed on established ferret brain maps. An important feature of the Ferretome database is the possibility to trace back entries in connectivity matrices to the original studies archived in the system. Currently, the Ferretome contains 50 reports on connections comprising 20 injection

  16. Visual counts as an index of White-Tailed Prairie Dog density

    USGS Publications Warehouse

    Menkens, George E.; Biggins, Dean E.; Anderson, Stanley H.

    1990-01-01

    Black-footed ferrets (Mustela nigripes) are depended on prairie dogs (Cynomys spp.) for food and shelter and were historically restricted to prairie dog towns (Anderson et al. 1986). Because ferrets and prairie dogs are closely associated, successful ferret management and conservation depends on successful prairie dog management. A critical component of any management program for ferrets will be monitoring prairie dog population dynamics on towns containing ferrets or on towns proposed as ferret reintroduction sites. Three techniques for estimating prairie dog population size and density are counts of plugged and reopened burrows (Tietjen and Matschke 1982), mark-recapture (Otis et al. 1978; Seber 1982, 1986; Menkens and Anderson 1989), and visual counts (Fagerstone and Biggins 1986, Knowles 1986). The technique of plugging burrows and counting the number reopened by prairie dogs is too time and labor intensive for population evaluation on a large number of towns or over large areas. Total burrow counts are not correlated with white-tailed prairie dog (C. leucurus) densities and thus cannot be used for populated evaluation (Menkens et al. 1988). Mark-recapture requires trapping that is expensive and time and labor intensive. Monitoring a large number of prairie dog populations using mark-recapture would be difficult. Alternatively a large number of populations could be monitored in short periods of time using the visual count technique (Fagerstone and Biggins 1986, Knowles 1986). However, the accuracy of visual counts has only been evaluated in a few locations. Thus, it is not known whether the relationship between counts and prairie dog density is consistent throughout the prairie dog's range. Our objective was to evaluate the potential of using visual counts as a rapid means of estimating white-tailed prairie dog density in prairie dog towns throughout Wyoming. We studied 18 white-tailed prairie dog towns in 4 white-tailed prairie dog complexes in Wyoming near

  17. Effect of anticholinesterase agents on airway epithelial function. Annual report, 15 July 1888-14 August 1989

    SciTech Connect

    Marin, M.G.

    1989-09-15

    Irreversible anticholinesterase compounds have potential serious health effects when employed as chemical warfare agents. Intoxication with these agents will cause an accumulation of acetylcholine at nerve muscle and nerve-gland junctions. Because tracheal glands have rich cholinergic innervation, we hypothesized that exposure to anticholinesterase agents, such as soman, would stimulate glandular secretion. This would cause pathological changes in the important lung defense mechanism of mucociliary clearance. Initial work on this contract revealed a dose-related increase in mucociliary transport in the ferret in response to soman. This effect could be inhibited by atropine but not by pralidoxime. The investigation described in this report relates to the effects of soman and its antidotes on glycoconjugate secretion of ferret trachea in vitro.

  18. A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels

    PubMed Central

    Martínez-Martínez, Maria Ángeles; De Juan Romero, Camino; Fernández, Virginia; Cárdenas, Adrián; Götz, Magdalena; Borrell, Víctor

    2016-01-01

    The outer subventricular zone (OSVZ) is a germinal layer playing key roles in the development of the neocortex, with particular relevance in gyrencephalic species such as human and ferret, where it contains abundant basal radial glia cells (bRGCs) that promote cortical expansion. Here we identify a brief period in ferret embryonic development when apical RGCs generate a burst of bRGCs that become founders of the OSVZ. After this period, bRGCs in the OSVZ proliferate and self-renew exclusively locally, thereby forming a self-sustained lineage independent from the other germinal layers. The time window for the brief period of OSVZ bRGC production is delineated by the coincident downregulation of Cdh1 and Trnp1, and their upregulation reduces bRGC production and prevents OSVZ seeding. This mechanism in cortical development may have key relevance in brain evolution and disease. PMID:27264089

  19. Possible Role of Fish and Frogs as Paratenic Hosts of Dracunculus medinensis, Chad

    PubMed Central

    Yabsley, Michael J.; Zirimwabagabo, Hubert; Bishop, Henry; Cleveland, Christopher A.; Maerz, John C.; Bringolf, Robert; Ruiz-Tiben, Ernesto

    2016-01-01

    Copepods infected with Dracunculus medinensis larvae collected from infected dogs in Chad were fed to 2 species of fish and tadpoles. Although they readily ingested copepods, neither species of fish, Nile tilapia (Oreochromis niloticus) nor fathead minnow (Pimephalis promelas), were found to harbor Dracunculus larvae when examined 2–3 weeks later. Tadpoles ingested copepods much more slowly; however, upon examination at the same time interval, tadpoles of green frogs (Lithobates [Rana] clamitans) were found to harbor small numbers of Dracunculus larvae. Two ferrets (Mustela putorius furo) were fed fish or tadpoles that had been exposed to infected copepods. Only the ferret fed tadpoles harbored developing Dracunculus larvae at necropsy 70–80 days postexposure. These observations confirm that D. medinensis, like other species in the genus Dracunculus, can readily survive and remain infective in potential paratenic hosts, especially tadpoles. PMID:27434418

  20. Microinjection of membrane-impermeable molecules into single neural stem cells in brain tissue.

    PubMed

    Wong, Fong Kuan; Haffner, Christiane; Huttner, Wieland B; Taverna, Elena

    2014-05-01

    This microinjection protocol allows the manipulation and tracking of neural stem and progenitor cells in tissue at single-cell resolution. We demonstrate how to apply microinjection to organotypic brain slices obtained from mice and ferrets; however, our technique is not limited to mouse and ferret embryos, but provides a means of introducing a wide variety of membrane-impermeable molecules (e.g., nucleic acids, proteins, hydrophilic compounds) into neural stem and progenitor cells of any developing mammalian brain. Microinjection experiments are conducted by using a phase-contrast microscope equipped with epifluorescence, a transjector and a micromanipulator. The procedure normally takes ∼2 h for an experienced researcher, and the entire protocol, including tissue processing, can be performed within 1 week. Thus, microinjection is a unique and versatile method for changing and tracking the fate of a cell in organotypic slice culture.

  1. Morbillivirus Experimental Animal Models: Measles Virus Pathogenesis Insights from Canine Distemper Virus

    PubMed Central

    da Fontoura Budaszewski, Renata; von Messling, Veronika

    2016-01-01

    Morbilliviruses share considerable structural and functional similarities. Even though disease severity varies among the respective host species, the underlying pathogenesis and the clinical signs are comparable. Thus, insights gained with one morbillivirus often apply to the other members of the genus. Since the Canine distemper virus (CDV) causes severe and often lethal disease in dogs and ferrets, it is an attractive model to characterize morbillivirus pathogenesis mechanisms and to evaluate the efficacy of new prophylactic and therapeutic approaches. This review compares the cellular tropism, pathogenesis, mechanisms of persistence and immunosuppression of the Measles virus (MeV) and CDV. It then summarizes the contributions made by studies on the CDV in dogs and ferrets to our understanding of MeV pathogenesis and to vaccine and drugs development. PMID:27727184

  2. Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential.

    PubMed

    Watanabe, Tokiko; Zhong, Gongxun; Russell, Colin A; Nakajima, Noriko; Hatta, Masato; Hanson, Anthony; McBride, Ryan; Burke, David F; Takahashi, Kenta; Fukuyama, Satoshi; Tomita, Yuriko; Maher, Eileen A; Watanabe, Shinji; Imai, Masaki; Neumann, Gabriele; Hasegawa, Hideki; Paulson, James C; Smith, Derek J; Kawaoka, Yoshihiro

    2014-06-11

    Wild birds harbor a large gene pool of influenza A viruses that have the potential to cause influenza pandemics. Foreseeing and understanding this potential is important for effective surveillance. Our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. To assess this risk, we generated and characterized a virus composed of avian influenza viral segments with high homology to the 1918 virus. This virus exhibited pathogenicity in mice and ferrets higher than that in an authentic avian influenza virus. Further, acquisition of seven amino acid substitutions in the viral polymerases and the hemagglutinin surface glycoprotein conferred respiratory droplet transmission to the 1918-like avian virus in ferrets, demonstrating that contemporary avian influenza viruses with 1918 virus-like proteins may have pandemic potential. PMID:24922572

  3. Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential

    PubMed Central

    Watanabe, Tokiko; Zhong, Gongxun; Russell, Colin A.; Nakajima, Noriko; Hatta, Masato; Hanson, Anthony; McBride, Ryan; Burke, David F.; Takahashi, Kenta; Fukuyama, Satoshi; Tomita, Yuriko; Maher, Eileen A.; Watanabe, Shinji; Imai, Masaki; Neumann, Gabriele; Hasegawa, Hideki; Paulson, James C.; Smith, Derek J.; Kawaoka, Yoshihiro

    2014-01-01

    Summary Wild birds harbor a large gene pool of influenza A viruses that have the potential to cause influenza pandemics. Foreseeing and understanding this potential is important for effective surveillance. Our phylogenetic and geographic analyses revealed the global prevalence of avian influenza virus genes whose proteins differ only a few amino acids from the 1918 pandemic influenza virus, suggesting that 1918-like pandemic viruses may emerge in the future. To assess this risk, we generated and characterized a virus composed of avian influenza viral segments with high homology to the 1918 virus. This virus exhibited higher pathogenicity in mice and ferrets than an authentic avian influenza virus. Further, acquisition of seven amino acid substitutions in the viral polymerases and the hemagglutinin surface glycoprotein conferred respiratory droplet transmission to the 1918-like avian virus in ferrets, demonstrating that contemporary avian influenza viruses with 1918 virus-like proteins may have pandemic potential. PMID:24922572

  4. Possible Role of Fish and Frogs as Paratenic Hosts of Dracunculus medinensis, Chad.

    PubMed

    Eberhard, Mark L; Yabsley, Michael J; Zirimwabagabo, Hubert; Bishop, Henry; Cleveland, Christopher A; Maerz, John C; Bringolf, Robert; Ruiz-Tiben, Ernesto

    2016-08-01

    Copepods infected with Dracunculus medinensis larvae collected from infected dogs in Chad were fed to 2 species of fish and tadpoles. Although they readily ingested copepods, neither species of fish, Nile tilapia (Oreochromis niloticus) nor fathead minnow (Pimephalis promelas), were found to harbor Dracunculus larvae when examined 2-3 weeks later. Tadpoles ingested copepods much more slowly; however, upon examination at the same time interval, tadpoles of green frogs (Lithobates [Rana] clamitans) were found to harbor small numbers of Dracunculus larvae. Two ferrets (Mustela putorius furo) were fed fish or tadpoles that had been exposed to infected copepods. Only the ferret fed tadpoles harbored developing Dracunculus larvae at necropsy 70-80 days postexposure. These observations confirm that D. medinensis, like other species in the genus Dracunculus, can readily survive and remain infective in potential paratenic hosts, especially tadpoles. PMID:27434418

  5. A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels.

    PubMed

    Martínez-Martínez, Maria Ángeles; De Juan Romero, Camino; Fernández, Virginia; Cárdenas, Adrián; Götz, Magdalena; Borrell, Víctor

    2016-01-01

    The outer subventricular zone (OSVZ) is a germinal layer playing key roles in the development of the neocortex, with particular relevance in gyrencephalic species such as human and ferret, where it contains abundant basal radial glia cells (bRGCs) that promote cortical expansion. Here we identify a brief period in ferret embryonic development when apical RGCs generate a burst of bRGCs that become founders of the OSVZ. After this period, bRGCs in the OSVZ proliferate and self-renew exclusively locally, thereby forming a self-sustained lineage independent from the other germinal layers. The time window for the brief period of OSVZ bRGC production is delineated by the coincident downregulation of Cdh1 and Trnp1, and their upregulation reduces bRGC production and prevents OSVZ seeding. This mechanism in cortical development may have key relevance in brain evolution and disease. PMID:27264089

  6. Development of cortical orientation selectivity in the absence of visual experience with contour

    PubMed Central

    Hussain, Shaista; Weliky, Michael

    2011-01-01

    Visual cortical neurons are selective for the orientation of lines, and the full development of this selectivity requires natural visual experience after eye opening. Here we examined whether this selectivity develops without seeing lines and contours. Juvenile ferrets were reared in a dark room and visually trained by being shown a movie of flickering, sparse spots. We found that despite the lack of contour visual experience, the cortical neurons of these ferrets developed strong orientation selectivity and exhibited simple-cell receptive fields. This finding suggests that overt contour visual experience is unnecessary for the maturation of orientation selectivity and is inconsistent with the computational models that crucially require the visual inputs of lines and contours for the development of orientation selectivity. We propose that a correlation-based model supplemented with a constraint on synaptic strength dynamics is able to account for our experimental result. PMID:21753023

  7. A restricted period for formation of outer subventricular zone defined by Cdh1 and Trnp1 levels.

    PubMed

    Martínez-Martínez, Maria Ángeles; De Juan Romero, Camino; Fernández, Virginia; Cárdenas, Adrián; Götz, Magdalena; Borrell, Víctor

    2016-06-06

    The outer subventricular zone (OSVZ) is a germinal layer playing key roles in the development of the neocortex, with particular relevance in gyrencephalic species such as human and ferret, where it contains abundant basal radial glia cells (bRGCs) that promote cortical expansion. Here we identify a brief period in ferret embryonic development when apical RGCs generate a burst of bRGCs that become founders of the OSVZ. After this period, bRGCs in the OSVZ proliferate and self-renew exclusively locally, thereby forming a self-sustained lineage independent from the other germinal layers. The time window for the brief period of OSVZ bRGC production is delineated by the coincident downregulation of Cdh1 and Trnp1, and their upregulation reduces bRGC production and prevents OSVZ seeding. This mechanism in cortical development may have key relevance in brain evolution and disease.

  8. The soft palate is an important site of adaptation for transmissible influenza viruses.

    PubMed

    Lakdawala, Seema S; Jayaraman, Akila; Halpin, Rebecca A; Lamirande, Elaine W; Shih, Angela R; Stockwell, Timothy B; Lin, Xudong; Simenauer, Ari; Hanson, Christopher T; Vogel, Leatrice; Paskel, Myeisha; Minai, Mahnaz; Moore, Ian; Orandle, Marlene; Das, Suman R; Wentworth, David E; Sasisekharan, Ram; Subbarao, Kanta

    2015-10-01

    Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference. PMID:26416728

  9. The soft palate is an important site of adaptation for transmissible influenza viruses.

    PubMed

    Lakdawala, Seema S; Jayaraman, Akila; Halpin, Rebecca A; Lamirande, Elaine W; Shih, Angela R; Stockwell, Timothy B; Lin, Xudong; Simenauer, Ari; Hanson, Christopher T; Vogel, Leatrice; Paskel, Myeisha; Minai, Mahnaz; Moore, Ian; Orandle, Marlene; Das, Suman R; Wentworth, David E; Sasisekharan, Ram; Subbarao, Kanta

    2015-10-01

    Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference.

  10. Adverse selection: does it preclude a competitive health insurance market?

    PubMed

    Sloan, F A

    1992-10-01

    In sum, although fixed dollar subsidies have the great virtue of ferreting out cross subsidies, society may not be satisfied with the results. The scenario described by Marquis is only one of many. People seem to want lifetime insurance offering low premiums if things go bad rather than premiums that change annually as health outcomes are realized [see, e.g., Light (1992)]. But nondiversible risk may be too great for a market in life contracts to exist.

  11. Video Otoscopy in Exotic Companion Mammals.

    PubMed

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ear disease is a common disorder seen in exotic companion mammals, especially in ferrets, rabbits, and rats. This article describes patient preparation, equipment, and video otoscopy technique in exotic companion mammals. This noninvasive technique facilitates accurate diagnosis of diseases affecting the external ear canal or middle ear. Moreover, therapeutic otoscopic evaluation of the external ear facilitates foreign body removal, external ear canal flushing, intralesional drug administration, myringotomy, and middle ear cavity flushing.

  12. Puncture-ejection of own egg by Least Bell's Vireo and potential implications for anti-parasitism defense

    USGS Publications Warehouse

    Sharp, Bryan L.; Peterson, Bonnie L.; Kus, Barbara E.

    2005-01-01

    A simple, papillary cystic adenocarcinoma of the mammary gland with metastases to the internal iliac and mesenteric lymph nodes, liver, and spleen was observed in a 12 to 13 year old female black-footed ferret (Mustela nigripes). Histologically, the tumor was aggressive, and lymphatic invasion was found. Attempts at virus isolation were negative. Other findings were bilateral infarcts in the kidneys, apparently resulting in acute renal shutdown and death, multiple thrombi in the right atrium, aortic arteriosclerosis, and focal interstitial pneumonia.

  13. Quantitative Characterization of Glycan-Receptor Binding of H9N2 Influenza A Virus Hemagglutinin

    PubMed Central

    Srinivasan, Karunya; Raman, Rahul; Jayaraman, Akila; Viswanathan, Karthik; Sasisekharan, Ram

    2013-01-01

    Avian influenza subtypes such as H5, H7 and H9 are yet to adapt to the human host so as to establish airborne transmission between humans. However, lab-generated reassorted viruses possessing hemagglutinin (HA) and neuraminidase (NA) genes from an avian H9 isolate and other genes from a human-adapted (H3 or H1) subtype acquired two amino acid changes in HA and a single amino acid change in NA that confer respiratory droplet transmission in ferrets. We previously demonstrated for human-adapted H1, H2 and H3 subtypes that quantitative binding affinity of their HA to α2→6 sialylated glycan receptors correlates with respiratory droplet transmissibility of the virus in ferrets. Such a relationship remains to be established for H9 HA. In this study, we performed a quantitative biochemical characterization of glycan receptor binding properties of wild-type and mutant forms of representative H9 HAs that were previously used in context of reassorted viruses in ferret transmission studies. We demonstrate here that distinct molecular interactions in the glycan receptor-binding site of different H9 HAs affect the glycan-binding specificity and affinity. Further we show that α2→6 glycan receptor-binding affinity of a mutant H9 HA carrying Thr-189→Ala amino acid change correlates with the respiratory droplet transmission in ferrets conferred by this change. Our findings contribute to a framework for monitoring the evolution of H9 HA by understanding effects of molecular changes in HA on glycan receptor-binding properties. PMID:23626667

  14. Drugs, Alcohol, and Independent Schools: A New Look at a Confounding Problem

    ERIC Educational Resources Information Center

    Cataldi, Libby

    2010-01-01

    The author's son Jeff is a heroin addict. He was not born this way, or maybe he was and the addiction was there, hiding, all through his childhood years. That is the thing with addiction, no one knows the cause. The author has spent a lot of time trying to ferret out the answer to why one of her two sons is an addict and the other is not. She now…

  15. A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

    PubMed Central

    Park, Dongsun; Jo, In Geun; Jang, Ja Young; Kwak, Tae Hwan; Yoo, Sang Ku; Jeon, Jeong Hee; Choi, Ehn-Kyoung; Joo, Seong Soo; Kim, Okjin; Kim, Yun-Bae

    2015-01-01

    The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents. PMID:26336585

  16. Orally Available Small-Molecule Polymerase Inhibitor Cures a Lethal Morbillivirus Infection

    PubMed Central

    Krumm, Stefanie A; Yan, Dan; Hovingh, Elise S; Evers, Taylor J; Enkirch, Theresa; Reddy, G. Prabhakar; Sun, Aiming; Saindane, Manohar T; Arrendale, Richard F; Painter, George; Liotta, Dennis C; Natchus, Michael G; von Messling, Veronika; Plemper, Richard K

    2014-01-01

    Measles virus (MeV) is a highly infectious morbillivirus responsible for major human morbidity and mortality in the non-vaccinated. The related, zoonotic canine distemper virus (CDV) induces morbillivirus disease in ferrets with 100% lethality. We report an orally available, shelf-stable pan-morbillivirus inhibitor that targets the viral polymerase. Prophylactic oral treatment of ferrets infected intranasally with a lethal CDV dose reduced viremia and prolonged survival. Equally infected ferrets receiving post-infection treatment at the onset of viremia showed low-grade viral loads, remained asymptomatic and recovered from infection, while control animals succumbed to the disease. Recovered animals also mounted a robust immune response and were protected against re-challenge with a lethal CDV dose. Drug-resistant viral recombinants were generated and found attenuated and transmission impaired compared to the genetic parent. These findings pioneer a path towards an effective morbillivirus therapy that aids measles eradication by synergizing vaccine and therapeutics to close herd immunity gaps due to vaccine refusal. PMID:24739760

  17. Studies on disease transmission in spacecraft environments. [as experienced onboard Skylab 1

    NASA Technical Reports Server (NTRS)

    Kenyon, A. J.

    1974-01-01

    The effects of the Skylab gas mixtures on general health and immunocompetence of mice and ferrets subjected to the Skylab space cabin environment (SCE) were initially studied in a stainless steel low pressure facility which was maintained at gas ratios of 30% nitrogen and 70% oxygen under 5 psia, and which consisted of two subchambers, that permitted mutual isolation of experimental groups and/or selective removal of animals without return of the entire cabin to ambient pressure was developed. The studies demonstrated that ferrets immunized with Brucella Strain 19 prior to being housed in SCE had decreased synthesis of IgG compared to their respective controls. The possibility of latent infections being responsible for stress-induced upper respiratory diseases of astronauts required that the role of neutralizing antibody as a function of antibody affinity/avidity be investigated. The model consisted of Aleutian disease virus (ADV) which infects ferrets and mink resulting in nonneutralized immune complexes. These studies demonstrated that early antibody to ADV had lower affinity/avidity than late antibody with respect to chronicity. These studies culminated in a description of antibody affinity, first isolation of ADV and its cultivation in vitro.

  18. Sylvatic plague vaccine: A new tool for conservation of threatened and endangered species?

    USGS Publications Warehouse

    Abbott, Rachel C.; Osorio, Jorge E.; Bunck, Christine M.; Rocke, Tonie E.

    2012-01-01

    Plague, a disease caused by Yersinia pestis introduced into North America about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. Current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. Although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. Alternative approaches to plague management are being tested, including vaccination. Currently, all black-footed ferret kits released for reintroduction are vaccinated against plague with an injectable protein vaccine, and even wild-born kits are captured and vaccinated at some locations. In addition, a novel, virally vectored, oral vaccine to prevent plague in wild prairie dogs has been developed and will soon be tested as an alternative, preemptive management tool. If demonstrated to be successful, oral vaccination of selected prairie dog populations could decrease the occurrence of plague epizootics in key locations, thereby reducing the source of bacteria while avoiding the indiscriminate environmental effects of dusting. Just as rabies in wild carnivores has largely been controlled through an active surveillance and oral vaccination program, we believe an integrated plague management strategy would be similarly enhanced with the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for prairie dogs. Control of plague in prairie dogs, and potentially other rodents, would significantly advance prairie dog conservation and black-footed ferret recovery.

  19. Pathophysiological analyses of cortical malformation using gyrencephalic mammals

    PubMed Central

    Masuda, Kosuke; Toda, Tomohisa; Shinmyo, Yohei; Ebisu, Haruka; Hoshiba, Yoshio; Wakimoto, Mayu; Ichikawa, Yoshie; Kawasaki, Hiroshi

    2015-01-01

    One of the most prominent features of the cerebral cortex of higher mammals is the presence of gyri. Because malformations of the cortical gyri are associated with severe disability in brain function, the mechanisms underlying malformations of the cortical gyri have been of great interest. Combining gyrencephalic carnivore ferrets and genetic manipulations using in utero electroporation, here we successfully recapitulated the cortical phenotypes of thanatophoric dysplasia (TD) by expressing fibroblast growth factor 8 in the ferret cerebral cortex. Strikingly, in contrast to TD mice, our TD ferret model showed not only megalencephaly but also polymicrogyria. We further uncovered that outer radial glial cells (oRGs) and intermediate progenitor cells (IPs) were markedly increased. Because it has been proposed that increased oRGs and/or IPs resulted in the appearance of cortical gyri during evolution, it seemed possible that increased oRGs and IPs underlie the pathogenesis of polymicrogyria. Our findings should help shed light on the molecular mechanisms underlying the formation and malformation of cortical gyri in higher mammals. PMID:26482531

  20. The multibasic cleavage site of the hemagglutinin of highly pathogenic A/Vietnam/1203/2004 (H5N1) avian influenza virus acts as a virulence factor in a host-specific manner in mammals.

    PubMed

    Suguitan, Amorsolo L; Matsuoka, Yumiko; Lau, Yuk-Fai; Santos, Celia P; Vogel, Leatrice; Cheng, Lily I; Orandle, Marlene; Subbarao, Kanta

    2012-03-01

    Highly pathogenic avian influenza (HPAI) viruses of the H5 and H7 subtypes typically possess multiple basic amino acids around the cleavage site (MBS) of their hemagglutinin (HA) protein, a recognized virulence motif in poultry. To determine the importance of the H5 HA MBS as a virulence factor in mammals, recombinant wild-type HPAI A/Vietnam/1203/2004 (H5N1) viruses that possessed (H5N1) or lacked (ΔH5N1) the H5 HA MBS were generated and evaluated for their virulence in BALB/c mice, ferrets, and African green monkeys (AGMs) (Chlorocebus aethiops). The presence of the H5 HA MBS was associated with lethality, significantly higher virus titers in the respiratory tract, virus dissemination to extrapulmonary organs, lymphopenia, significantly elevated levels of proinflammatory cytokines and chemokines, and inflammation in the lungs of mice and ferrets. In AGMs, neither H5N1 nor ΔH5N1 virus was lethal and neither caused clinical symptoms. The H5 HA MBS was associated with mild enhancement of replication and delayed virus clearance. Thus, the contribution of H5 HA MBS to the virulence of the HPAI H5N1 virus varies among mammalian hosts and is most significant in mice and ferrets and less remarkable in nonhuman primates. PMID:22205751

  1. Identification, Characterization, and Natural Selection of Mutations Driving Airborne Transmission of A/H5N1 virus

    PubMed Central

    Linster, Martin; van Boheemen, Sander; de Graaf, Miranda; Schrauwen, Eefje J. A.; Lexmond, Pascal; Mänz, Benjamin; Bestebroer, Theo M.; Baumann, Jan; van Riel, Debby; Rimmelzwaan, Guus F.; Osterhaus, Albert D.M.E.; Matrosovich, Mikhail; Fouchier, Ron A. M.; Herfst, Sander

    2014-01-01

    SUMMARY Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3 linked to α2,6 linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments. PMID:24725402

  2. Sylvatic plague vaccine: a new tool for conservation of threatened and endangered species?

    PubMed

    Abbott, Rachel C; Osorio, Jorge E; Bunck, Christine M; Rocke, Tonie E

    2012-09-01

    Plague, a disease caused by Yersinia pestis introduced into North America about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. Current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. Although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. Alternative approaches to plague management are being tested, including vaccination. Currently, all black-footed ferret kits released for reintroduction are vaccinated against plague with an injectable protein vaccine, and even wild-born kits are captured and vaccinated at some locations. In addition, a novel, virally vectored, oral vaccine to prevent plague in wild prairie dogs has been developed and will soon be tested as an alternative, preemptive management tool. If demonstrated to be successful, oral vaccination of selected prairie dog populations could decrease the occurrence of plague epizootics in key locations, thereby reducing the source of bacteria while avoiding the indiscriminate environmental effects of dusting. Just as rabies in wild carnivores has largely been controlled through an active surveillance and oral vaccination program, we believe an integrated plague management strategy would be similarly enhanced with the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for prairie dogs. Control of plague in prairie dogs, and potentially other rodents, would significantly advance prairie dog conservation and black-footed ferret recovery. PMID:22846964

  3. Sylvatic plague vaccine: a new tool for conservation of threatened and endangered species?

    PubMed

    Abbott, Rachel C; Osorio, Jorge E; Bunck, Christine M; Rocke, Tonie E

    2012-09-01

    Plague, a disease caused by Yersinia pestis introduced into North America about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. Current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. Although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. Alternative approaches to plague management are being tested, including vaccination. Currently, all black-footed ferret kits released for reintroduction are vaccinated against plague with an injectable protein vaccine, and even wild-born kits are captured and vaccinated at some locations. In addition, a novel, virally vectored, oral vaccine to prevent plague in wild prairie dogs has been developed and will soon be tested as an alternative, preemptive management tool. If demonstrated to be successful, oral vaccination of selected prairie dog populations could decrease the occurrence of plague epizootics in key locations, thereby reducing the source of bacteria while avoiding the indiscriminate environmental effects of dusting. Just as rabies in wild carnivores has largely been controlled through an active surveillance and oral vaccination program, we believe an integrated plague management strategy would be similarly enhanced with the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for prairie dogs. Control of plague in prairie dogs, and potentially other rodents, would significantly advance prairie dog conservation and black-footed ferret recovery.

  4. An essential role of SVZ progenitors in cortical folding in gyrencephalic mammals

    PubMed Central

    Toda, Tomohisa; Shinmyo, Yohei; Dinh Duong, Tung Anh; Masuda, Kosuke; Kawasaki, Hiroshi

    2016-01-01

    Because folding of the cerebral cortex in the mammalian brain is believed to be crucial for higher brain functions, the mechanisms underlying its formation during development and evolution are of great interest. Although it has been proposed that increased neural progenitors in the subventricular zone (SVZ) are responsible for making cortical folds, their roles in cortical folding are still largely unclear, mainly because genetic methods for gyrencephalic mammals had been poorly available. Here, by taking an advantage of our newly developed in utero electroporation technique for the gyrencephalic brain of ferrets, we investigated the role of SVZ progenitors in cortical folding. We found regional differences in the abundance of SVZ progenitors in the developing ferret brain even before cortical folds began to be formed. When Tbr2 transcription factor was inhibited, intermediate progenitor cells were markedly reduced in the ferret cerebral cortex. Interestingly, outer radial glial cells were also reduced by inhibiting Tbr2. We uncovered that reduced numbers of SVZ progenitors resulted in impaired cortical folding. When Tbr2 was inhibited, upper cortical layers were preferentially reduced in gyri compared to those in sulci. Our findings indicate the biological importance of SVZ progenitors in cortical folding in the gyrencephalic brain. PMID:27403992

  5. Abundant Occurrence of Basal Radial Glia in the Subventricular Zone of Embryonic Neocortex of a Lissencephalic Primate, the Common Marmoset Callithrix jacchus

    PubMed Central

    Kelava, Iva; Reillo, Isabel; Murayama, Ayako Y.; Kalinka, Alex T.; Stenzel, Denise; Tomancak, Pavel; Matsuzaki, Fumio; Lebrand, Cécile; Sasaki, Erika; Schwamborn, Jens C.; Okano, Hideyuki; Borrell, Víctor

    2012-01-01

    Subventricular zone (SVZ) progenitors are a hallmark of the developing neocortex. Recent studies described a novel type of SVZ progenitor that retains a basal process at mitosis, sustains expression of radial glial markers, and is capable of self-renewal. These progenitors, referred to here as basal radial glia (bRG), occur at high relative abundance in the SVZ of gyrencephalic primates (human) and nonprimates (ferret) but not lissencephalic rodents (mouse). Here, we analyzed the occurrence of bRG cells in the embryonic neocortex of the common marmoset Callithrix jacchus, a near-lissencephalic primate. bRG cells, expressing Pax6, Sox2 (but not Tbr2), glutamate aspartate transporter, and glial fibrillary acidic protein and retaining a basal process at mitosis, occur at similar relative abundance in the marmoset SVZ as in human and ferret. The proportion of progenitors in M-phase was lower in embryonic marmoset than developing ferret neocortex, raising the possibility of a longer cell cycle. Fitting the gyrification indices of 26 anthropoid species to an evolutionary model suggested that the marmoset evolved from a gyrencephalic ancestor. Our results suggest that a high relative abundance of bRG cells may be necessary, but is not sufficient, for gyrencephaly and that the marmoset's lissencephaly evolved secondarily by changing progenitor parameters other than progenitor type. PMID:22114084

  6. Quantitative comparison of autoradioluminographic and radiometric tissue distribution studies using carbon-14 labeled xenobiotics.

    PubMed

    Potchoiba, M J; West, M; Nocerini, M R

    1998-03-01

    The tissue distribution of two 14C drugs were quantitatively compared using the techniques of whole body autoradioluminography (WBAL) and radiometry. Quantitative analysis of tissue radioactivity in whole body cryosections was accomplished from storage phosphor images using the MicroComputer Imaging Device. After obtaining whole body sections from four frozen rats and three frozen ferrets, each WBAL-sectioned specimen was partially thawed before obtaining tissue samples for radiometric analysis. For all tissues examined, concentrations of radioactivity determined by WBAL were comparable with those determined by dissection and liquid scintillation analysis (DLSA), except for renal tissue obtained from different kidneys of the same ferret and for rat ocular tissues. A 2-fold difference was observed between WBAL and DLSA evaluations of radioactivity in the contralateral kidneys of one ferret. DLSA evaluation only provided an assessment of total radioactivity in the eye, whereas WBAL evaluation determined the selective distribution of radioactivity to ocular tissues. Resolution in DLSA evaluation of ocular tissues was restricted by limitations of the dissection procedure. These results indicated that the quantitation of tissue radioactivity by WBAL was as precise as DLSA evaluation, and WBAL also provided results to the quantitative distribution of radioactivity to localized sites in organs not feasible by DLSA.

  7. Mustelidae are natural hosts of Staphylococcus delphini group A.

    PubMed

    Guardabassi, Luca; Schmidt, Kristina Runge; Petersen, Tina Steiner; Espinosa-Gongora, Carmen; Moodley, Arshnee; Agersø, Yvonne; Olsen, John Elmerdahl

    2012-10-12

    According to the current taxonomy, the Staphylococcus intermedius group (SIG) comprises of at least three distinct species. While S. intermedius and S. pseudintermedius are associated with specific hosts (pigeons and dogs, respectively), the natural host of S. delphini remains unclear. We analysed 158 SIG isolates from less studied animal species belonging to the order Carnivora, including mink (n=118), fox (n=33), badger (n=6) and ferret (n=1). Species identification was performed by nuc PCR in combination with sodA sequence analysis and pta PCR restriction fragment length polymorphism (RFLP). The results showed a consistent association between host and bacterial species. All isolates from minks, ferret and badgers belonged to S. delphini group A, whereas all fox isolates except one were identified as S. pseudintermedius. The remaining fox isolate belonged to S. delphini group A. The results indicate that Mustelidae such as minks, ferrets and badgers are natural hosts of S. delphini group A. This is in contrast with Canidae, which are primarily colonized and infected with S. pseudintermedius. These findings suggest that coagulase-positive staphylococcal species may have evolved and diverged through host adaptation.

  8. Pathophysiological analyses of cortical malformation using gyrencephalic mammals.

    PubMed

    Masuda, Kosuke; Toda, Tomohisa; Shinmyo, Yohei; Ebisu, Haruka; Hoshiba, Yoshio; Wakimoto, Mayu; Ichikawa, Yoshie; Kawasaki, Hiroshi

    2015-01-01

    One of the most prominent features of the cerebral cortex of higher mammals is the presence of gyri. Because malformations of the cortical gyri are associated with severe disability in brain function, the mechanisms underlying malformations of the cortical gyri have been of great interest. Combining gyrencephalic carnivore ferrets and genetic manipulations using in utero electroporation, here we successfully recapitulated the cortical phenotypes of thanatophoric dysplasia (TD) by expressing fibroblast growth factor 8 in the ferret cerebral cortex. Strikingly, in contrast to TD mice, our TD ferret model showed not only megalencephaly but also polymicrogyria. We further uncovered that outer radial glial cells (oRGs) and intermediate progenitor cells (IPs) were markedly increased. Because it has been proposed that increased oRGs and/or IPs resulted in the appearance of cortical gyri during evolution, it seemed possible that increased oRGs and IPs underlie the pathogenesis of polymicrogyria. Our findings should help shed light on the molecular mechanisms underlying the formation and malformation of cortical gyri in higher mammals. PMID:26482531

  9. Optimization of Recombinant Adeno-Associated Virus-Mediated Expression for Large Transgenes, Using a Synthetic Promoter and Tandem Array Enhancers

    PubMed Central

    Yan, Ziying; Sun, Xingshen; Feng, Zehua; Li, Guiying; Fisher, John T.; Stewart, Zoe A.

    2015-01-01

    Abstract The packaging capacity of recombinant adeno-associated viral (rAAV) vectors limits the size of the promoter that can be used to express the 4.43-kb cystic fibrosis transmembrane conductance regulator (CFTR) cDNA. To circumvent this limitation, we screened a set of 100-mer synthetic enhancer elements, composed of ten 10-bp repeats, for their ability to augment CFTR transgene expression from a short 83-bp synthetic promoter in the context of an rAAV vector designed for use in the cystic fibrosis (CF) ferret model. Our initial studies assessing transcriptional activity in monolayer (nonpolarized) cultures of human airway cell lines and primary ferret airway cells revealed that three of these synthetic enhancers (F1, F5, and F10) significantly promoted transcription of a luciferase transgene in the context of plasmid transfection. Further analysis in polarized cultures of human and ferret airway epithelia at an air–liquid interface (ALI), as well as in the ferret airway in vivo, demonstrated that the F5 enhancer produced the highest level of transgene expression in the context of an AAV vector. Furthermore, we demonstrated that increasing the size of the viral genome from 4.94 to 5.04 kb did not significantly affect particle yield of the vectors, but dramatically reduced the functionality of rAAV-CFTR vectors because of small terminal deletions that extended into the CFTR expression cassette of the 5.04-kb oversized genome. Because rAAV-CFTR vectors greater than 5 kb in size are dramatically impaired with respect to vector efficacy, we used a shortened ferret CFTR minigene with a 159-bp deletion in the R domain to construct an rAAV vector (AV2/2.F5tg83-fCFTRΔR). This vector yielded an ∼17-fold increase in expression of CFTR and significantly improved Cl– currents in CF ALI cultures. Our study has identified a small enhancer/promoter combination that may have broad usefulness for rAAV-mediated CF gene therapy to the airway. PMID:25763813

  10. A New Orally Active, Aminothiol Radioprotector-Free of Nausea and Hypotension Side Effects at Its Highest Radioprotective Doses

    SciTech Connect

    Soref, Cheryl M.; Hacker, Timothy A.; Fahl, William E.

    2012-04-01

    Purpose: A new aminothiol, PrC-210, was tested for orally conferred radioprotection (rats, mice; 9.0 Gy whole-body, which was otherwise lethal to 100% of the animals) and presence of the debilitating side effects (nausea/vomiting, hypotension/fainting) that restrict use of the current aminothiol, amifostine (Ethyol, WR-2721). Methods and Materials: PrC-210 in water was administered to rats and mice at times before irradiation, and percent-survival was recorded for 60 days. Subcutaneous (SC) amifostine (positive control) or SC PrC-210 was administered to ferrets (Mustela putorius furo) and retching/emesis responses were recorded. Intraperitoneal amifostine (positive control) or PrC-210 was administered to arterial cannulated rats to score drug-induced hypotension. Results: Oral PrC-210 conferred 100% survival in rat and mouse models against an otherwise 100% lethal whole-body radiation dose (9.0 Gy). Oral PrC-210, administered by gavage 30-90 min before irradiation, conferred a broad window of radioprotection. The comparison of PrC-210 and amifostine side effects was striking because there was no retching or emesis in 10 ferrets treated with PrC-210 and no induced hypotension in arterial cannulated rats treated with PrC-210. The tested PrC-210 doses were the ferret and rat equivalent doses of the 0.5 maximum tolerated dose (MTD) PrC-210 dose in mice. The human equivalent of this mouse 0.5 MTD PrC-210 dose would likely be the highest PrC-210 dose used in humans. By comparison, the mouse 0.5 MTD amifostine dose, 400 {mu}g/g body weight (equivalent to the human amifostine dose of 910 mg/m{sup 2}), when tested at equivalent ferret and rat doses in the above models produced 100% retching/vomiting in ferrets and 100% incidence of significant, progressive hypotension in rats. Conclusions: The PrC-210 aminothiol, with no detectable nausea/vomiting or hypotension side effects in these preclinical models, is a logical candidate for human drug development to use in healthy

  11. Mammalian pathogenesis of oseltamivir-resistant pandemic (H1N1) 2009 influenza virus isolated in South Korea.

    PubMed

    Kwon, Donghyok; Shin, Kyeongcheol; Kim, Su-Jin; Lee, Joo-Yeon; Kang, Chun

    2014-06-24

    Oseltamivir, a neuraminidase (NA) inhibitor, has been widely used for the treatment of patients infected with the pandemic (H1N1) 2009 influenza virus. With the increasing use of oseltamivir, drug-resistant mutants emerged rapidly and 11 cases of resistant viruses were detected during the 2009 H1N1 pandemic in South Korea. To better understand the differences between oseltamivir-susceptible and oseltamivir-resistant virus, we compared the replication and pathogenesis of the NA H275Y mutant virus, A/Gyeongnam/1820/2009, in ferrets and mice with those of oseltamivir-susceptible A/Korea/01/2009 virus. Oseltamivir-resistant virus infected ferrets showed mild clinical signs and the virus replicated well in the upper respiratory tract and slightly in the lower respiratory tract. No virus was detected in the extrapulmonary organs. Severe bronchopneumonia and thickening of alveolar walls were detected in the lungs. Viral antigens were detected mainly in the bronchiolar epithelial cells, cells present in the interstitial septa, pneumocytes and peribronchial glands with severe peribronchitis. A/Gyeongnam/1820/2009 virus-infected mice showed weight loss and the virus replicated in lungs with high titer. Histopathologically, the mice showed mild to moderate alveolitis, interstitial pneumonia and perivascular lymphoid tissue hyperplasia. In lungs, bronchiolar epithelial cells, pneumocytes and interstitial inflammatory cells were infected by influenza virus and trachea epithelial cells were the sites of infection. When compared with the results of A/Korea/01/2009 oseltamivir-susceptible pandemic influenza virus, an oseltamivir-resistant virus isolated in South Korea showed fewer pathogenic properties in ferrets and similar fitness in mice.

  12. Chronic detachable headphones for acoustic stimulation in freely moving animals.

    PubMed

    Nodal, Fernando R; Keating, Peter; King, Andrew J

    2010-05-30

    A growing number of studies of auditory processing are being carried out in awake, behaving animals, creating a need for precisely controlled sound delivery without restricting head movements. We have designed a system for closed-field stimulus presentation in freely moving ferrets, which comprises lightweight, adjustable headphones that can be consistently positioned over the ears via a small, skull-mounted implant. The invasiveness of the implant was minimized by simplifying its construction and using dental adhesive only for attaching it to the skull, thereby reducing the surgery required and avoiding the use of screws or other anchoring devices. Attaching the headphones to a chronic implant also reduced the amount of contact they had with the head and ears, increasing the willingness of the animals to wear them. We validated sound stimulation via the headphones in ferrets trained previously in a free-field task to localize stimuli presented from one of two loudspeakers. Noise bursts were delivered binaurally over the headphones and interaural level differences (ILDs) were introduced to allow the sound to be lateralized. Animals rapidly transferred from the free-field task to indicate the perceived location of the stimulus presented over headphones. They showed near perfect lateralization with a 5 dB ILD, matching the scores achieved in the free-field task. As expected, the ferrets' performance declined when the ILD was reduced in value. This closed-field system can easily be adapted for use in other species, and provides a reliable means of presenting closed-field stimuli whilst monitoring behavioral responses in freely moving animals.

  13. Detection of Neospora caninum in wild carnivorans in Great Britain.

    PubMed

    Bartley, P M; Wright, S E; Zimmer, I A; Roy, S; Kitchener, A C; Meredith, A; Innes, E A; Katzer, F

    2013-02-18

    Samples of brain and other tissues were collected from 99 ferrets (Mustela furo), 83 red foxes (Vulpes vulpes), 70 European polecats (Mustela putorius), 65 American mink (Neovison vison), 64 Eurasian badgers (Meles meles) and 9 stoats (Mustela erminea), from around Great Britain. DNA was extracted from approximately 1g of tissue and tested by specific nested ITS1 PCR for Neospora caninum. The results from the PCR demonstrated that Neospora specific DNA was detected in all species of wild carnivorans with the exception of the stoats (0/9). Neospora DNA positive samples were detected in: polecats 18.6% (13/70), badgers 10.9% (7/64), ferrets 10.1% (10/99), foxes 4.8% (4/83) and mink 4.6% (3/65). In the badgers N. caninum DNA positive samples were found in brain (n=2), liver (n=2) and neck muscle (n=3). Selected positive ITS1 DNA sequences were submitted to Genbank. Sequence UKwildlife1 (accession number JX857862) was found in two badgers, whilst UKwildlife2 and UKwildlife3 (accession numbers JX857863 and JX857864 respectively) were found in ferrets, all three sequences demonstrated point mutations at a single base, while sequence UKwildlife4 (accession number JX857865) was found in all the species that tested positive and showed complete identity when compared against published reference sequences for: N. caninum (Nc Liverpool isolate, EU564166). Our data shows that almost all the wild carnivoran mammal species tested are intermediate hosts for N. caninum and are therefore capable of acting as reservoirs of infection for other species. These species could also act as useful sentinel species, demonstrating the presence of the parasite in particular geographical and environmental locations.

  14. Public Health Responses to Reemergence of Animal Rabies, Taiwan, July 16–December 28, 2013

    PubMed Central

    Huang, Angela Song-En; Chen, Wan-Chin; Huang, Wan-Ting; Huang, Shih-Tse; Lo, Yi-Chun; Wei, Sung-Hsi; Kuo, Hung-Wei; Chan, Pei-Chun; Hung, Min-Nan; Liu, Yu-Lun; Mu, Jung-Jung; Yang, Jyh-Yuan; Liu, Ding-Ping; Chou, Jih-Haw; Chuang, Jen-Hsiang; Chang, Feng-Yee

    2015-01-01

    Taiwan had been free of indigenous human and animal rabies case since canine rabies was eliminated in 1961. In July 2013, rabies was confirmed among three wild ferret-badgers, prompting public health response to prevent human rabies cases. This descriptive study reports the immediate response to the reemergence of rabies in Taiwan. Response included enhanced surveillance for human rabies cases by testing stored cerebrospinal fluids (CSF) from patients with encephalitides of unknown cause by RT-PCR, prioritizing vaccine use for postexposure prophylaxis (PEP) during periods of vaccine shortage and subsequent expansion of PEP, surveillance of animal bites using information obtained from vaccine application, roll out of preexposure prophylaxis (PrEP) with vaccine stock restoration, surveillance for adverse events following immunization (AEFI), and ensuring surge capacity to respond to general public inquiries by phone and training for healthcare professionals. Enhanced surveillance for human rabies found no cases after testing 205 stored CSF specimens collected during January 2010–July 2013. During July 16 to December 28, 2013, we received 8,241 rabies PEP application; 6,634 (80.5%) were consistent with recommendations. Among the 6,501persons who received at least one dose of rabies vaccine postexposure, 4,953 (76.2%) persons who were bitten by dogs; only 59 (0.9%) persons were bitten by ferret-badgers. During the study period, 6,247 persons received preexposure prophylaxis. There were 23 reports of AEFI; but no anaphylaxis, Guillain-Barré syndrome, or acute disseminated encephalomyelitis were found. During the study period, there were 40,312 calls to the Taiwan Centers for Disease Control hotline, of which, 8,692 (22%) were related to rabies. Recent identification of rabies among ferret-badgers in a previously rabies-free country prompted rapid response. To date, no human rabies has been identified. Continued multifaceted surveillance and interministerial

  15. H5N1 influenza viruses: facts, not fear.

    PubMed

    Palese, Peter; Wang, Taia T

    2012-02-14

    The ongoing controversy over publication of two studies involving the transmission in ferrets of H5N1 (H5) subtype influenza viruses and the recommendations of the National Science Advisory Board for Biosecurity to redact key details in the manuscripts call for an examination of relevant scientific facts. In addition, there are calls in the media to destroy the viruses, curtail future research in this area, and protect the public from such "frightening" research efforts. Fear needs to be put to rest with solid science and not speculation.

  16. Generation and Characterization of Live Attenuated Influenza A(H7N9) Candidate Vaccine Virus Based on Russian Donor of Attenuation

    PubMed Central

    Shcherbik, Svetlana; Pearce, Nicholas; Balish, Amanda; Jones, Joyce; Thor, Sharmi; Davis, Charles Todd; Pearce, Melissa; Tumpey, Terrence; Cureton, David; Chen, Li-Mei; Villanueva, Julie; Bousse, Tatiana L.

    2015-01-01

    Background Avian influenza A (H7N9) virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV) are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV) to provide temperature sensitive, cold-adapted and attenuated phenotypes. Methodology/Principal Findings LAIV candidate A/Anhui/1/2013(H7N9)-CDC-LV7A (abbreviated as CDC-LV7A), based on the Russian MDV, A/Leningrad/134/17/57 (H2N2), was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering) in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9)RG-LV1 and A(H7N9)RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9) virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7. Conclusions/Significance Our data indicate that the A/Anhui/1/2013(H7N9)-CDC-LV7A reassortant virus is a safe and

  17. Mammalian Pathogenesis and Transmission of H7N9 Influenza Viruses from Three Waves, 2013-2015

    PubMed Central

    Belser, Jessica A.; Creager, Hannah M.; Sun, Xiangjie; Gustin, Kortney M.; Jones, Tara; Shieh, Wun-Ju; Maines, Taronna R.

    2016-01-01

    ABSTRACT Three waves of human infection with H7N9 influenza viruses have concluded to date, but only viruses within the first wave (isolated between March and September 2013) have been extensively studied in mammalian models. While second- and third-wave viruses remain closely linked phylogenetically and antigenically, even subtle molecular changes can impart critical shifts in mammalian virulence. To determine if H7N9 viruses isolated from humans during 2013 to 2015 have maintained the phenotype first identified among 2013 isolates, we assessed the ability of first-, second-, and third-wave H7N9 viruses isolated from humans to cause disease in mice and ferrets and to transmit among ferrets. Similar to first-wave viruses, H7N9 viruses from 2013 to 2015 were highly infectious in mice, with lethality comparable to that of the well-studied A/Anhui/1/2013 virus. Second- and third-wave viruses caused moderate disease in ferrets, transmitted efficiently to cohoused, naive contact animals, and demonstrated limited transmissibility by respiratory droplets. All H7N9 viruses replicated efficiently in human bronchial epithelial cells, with subtle changes in pH fusion threshold identified between H7N9 viruses examined. Our results indicate that despite increased genetic diversity and geographical distribution since their initial detection in 2013, H7N9 viruses have maintained a pathogenic phenotype in mammals and continue to represent an immediate threat to public health. IMPORTANCE H7N9 influenza viruses, first isolated in 2013, continue to cause human infection and represent an ongoing public health threat. Now entering the fourth wave of human infection, H7N9 viruses continue to exhibit genetic diversity in avian hosts, necessitating continuous efforts to monitor their pandemic potential. However, viruses isolated post-2013 have not been extensively studied, limiting our understanding of potential changes in virus-host adaptation. In order to ensure that current research

  18. Pandemic potential of avian influenza A (H7N9) viruses.

    PubMed

    Watanabe, Tokiko; Watanabe, Shinji; Maher, Eileen A; Neumann, Gabriele; Kawaoka, Yoshihiro

    2014-11-01

    Avian influenza viruses rarely infect humans, but the recently emerged avian H7N9 influenza viruses have caused sporadic infections in humans in China, resulting in 440 confirmed cases with 122 fatalities as of 16 May 2014. In addition, epidemiologic surveys suggest that there have been asymptomatic or mild human infections with H7N9 viruses. These viruses replicate efficiently in mammals, show limited transmissibility in ferrets and guinea pigs, and possess mammalian-adapting amino acid changes that likely contribute to their ability to infect mammals. In this review, we summarize the characteristic features of the novel H7N9 viruses and assess their pandemic potential.

  19. The role of multiple wildlife hosts in the persistence and spread of bovine tuberculosis in New Zealand

    PubMed Central

    Barron, MC; Tompkins, DM; Ramsey, DSL; Bosson, MAJ

    2015-01-01

    Abstract AIM: To explore how the inclusion of multi-host dynamics affects the predicted prevalence of bovine tuberculosis (TB) in possums and other host species following the current best practice for control of TB in large difficult and remote areas, to identify which host species are responsible for changes in predicted prevalence, and whether TB can persist in possum-free host communities. METHODS: Multi-host TB models were constructed, comprising three host species with density-dependent population growth, density-dependent disease transmission and susceptible and infected classes. Models were parameterised for two case studies of current concern in New Zealand, namely chronic TB persistence in a possum-deer-pig complex in extensive forest, and in a possum-pig-ferret complex in unforested semi-arid shrub and grasslands. Persistence of TB in the face of best practice possum control was evaluated from model simulations, and the contribution of different hosts to persistence of TB was assessed by removing each host species in turn from the simulations. A sensitivity test explored how different parameter values affected modelled persistence of TB. RESULTS: The forest multi-host model-predicted amplification of TB prevalence due to the presence of pigs. The presence of pigs and/or deer did not jeopardise the success of best practice possum control in eradicating TB from the system, as pigs and deer are effectively end-hosts for TB. Sensitivity analyses indicated these interpretations were robust to uncertainty in model parameter values. The grassland system model predicted that the multi-host species complex could potentially lead to failure of eradication of TB under possum-only control, due to TB persisting in ferret and pig populations in the absence of possum hosts through reciprocal scavenging, resulting in spillback transmission to possums once their populations had started to recover from control. CONCLUSIONS: With respect to management of TB, for modelled

  20. Modeling spatial patterns in the visual cortex

    NASA Astrophysics Data System (ADS)

    Daza C., Yudy Carolina; Tauro, Carolina B.; Tamarit, Francisco A.; Gleiser, Pablo M.

    2014-10-01

    We propose a model for the formation of patterns in the visual cortex. The dynamical units of the model are Kuramoto phase oscillators that interact through a complex network structure embedded in two dimensions. In this way the strength of the interactions takes into account the geographical distance between units. We show that for different parameters, clustered or striped patterns emerge. Using the structure factor as an order parameter we are able to quantitatively characterize these patterns and present a phase diagram. Finally, we show that the model is able to reproduce patterns with cardinal preference, as observed in ferrets.

  1. Rapid population growth of a critically endangered carnivore.

    PubMed

    Grenier, M B; McDonald, D B; Buskirk, S W

    2007-08-10

    Reintroductions of endangered species are controversial because of high costs and frequent failures. However, the population of black-footed ferrets descended from animals released in Shirley Basin, Wyoming, from 1991 to 1994 has grown rapidly after a decline to a low of five animals in 1997. Beginning around 2000, the population grew rapidly to an estimated 223 (95% confidence interval is 192 to 401) individuals in 2006. Matrix population modeling shows the importance of survival and reproduction during the first year of life, reflecting an uncommon life history for an endangered mammalian carnivore. Recovery of the species may benefit from more opportunistic and widespread releases. PMID:17690288

  2. Pandemic potential of H7N9 influenza viruses

    PubMed Central

    Watanabe, Tokiko; Watanabe, Shinji; Maher, Eileen A.; Neumann, Gabriele; Kawaoka, Yoshihiro

    2014-01-01

    Avian influenza viruses rarely infect humans, but the recently emerged avian H7N9 influenza viruses have caused sporadic infections in humans in China, resulting in 440 confirmed cases with 122 fatalities as of May 16, 2014. In addition, epidemiologic surveys suggest that there have been asymptomatic or mild human infections with H7N9 viruses. These viruses replicate efficiently in mammals, show limited transmissibility in ferrets and guinea pigs, and possess mammalian-adapting amino acid changes that likely contribute to their ability to infect mammals. Here, we summarize the characteristic features of the novel H7N9 viruses and assess their pandemic potential. PMID:25264312

  3. Modeling human influenza infection in the laboratory

    PubMed Central

    Radigan, Kathryn A; Misharin, Alexander V; Chi, Monica; Budinger, GR Scott

    2015-01-01

    Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection. PMID:26357484

  4. Viral Injection and Cranial Window Implantation for In Vivo Two-Photon Imaging.

    PubMed

    Smith, Gordon B; Fitzpatrick, David

    2016-01-01

    Two-photon (2P) imaging has proven to be a powerful tool for investigating neural structure and function both in brain slices and in intact systems. In vivo 2P imaging presents significant challenges in sample preparation, which are exacerbated in non-murine species. Here, we describe procedures for the effective virally mediated labeling of neurons and for the implantation of cranial windows for imaging. The procedures described here are applicable to a range of species, including mice, and are routinely used in ferrets and tree shrews to provide large-scale labeling of cortical volumes and high-quality imaging data. PMID:27515080

  5. Markers of Renal Function and Injury

    SciTech Connect

    Ragan, Harvey A.; Weller, Richard E.

    1999-04-15

    Designed to aid the laboratory animal veterinarian, researcher, or toxicologist in the proper evaluation of organ function, this updated and revised edition provides the only comprehensive reference of the clinical chemistry of laboratory animals. With contributions from recognized experts in the field, new chapters are included that focus on the pig and the ferret, while many chapters have been rewritten. Expanded coverage was given to urine chemistry, hormones, including melatonin, and the control mechanisms of analytes. Reference values are given in both conventional and S.I. units.

  6. Effect of anticholinesterase agents on airway epithelial function. Annual report, 15 July 1985-14 July 1986

    SciTech Connect

    Marin, M.G.

    1986-08-01

    Irreversible anticholinesterase compounds have potential serious deleterious health effects when employed as chemical warfare agents. Intoxication with these agents will cause an accumulation of acetylcholine at nerve muscle and nerve gland junctions. Because tracheal submucosal glands have rich cholinergic innervation, we hypothesized that exposure to anticholinesterase agents, such as soman, would stimulate glandular secretion. This would cause pathological changes in the important lung defense mechanism of mucociliary clearance. Despite the potential importance of anticholinesterases to lung function, little information was available concerning the effects of these agents on mucociliary transport. The initial technical objectives of this proposal were to modify a technique and to utilize it to study mucociliary transport in the ferret in vivo. Utilizing this technique, we have begun to define baseline mucociliary transport rates in anesthetized ferrets. Furthermore, studies have been under way to determine the effect of atropine on this transport rate. This report delineates the progress thus far. It was shown that mucociliary transport remains relatively constant over a 5 1/2-hour time period, with a mean transport rate between 16.7 and 20.7 mm/min. Initial studies utilizing atropine indicate that there is a decrease in transport rate following the administration of atropine, which reaches a nadir at about 2 hours following administration of atropine.

  7. Focused antibody response to influenza linked to antigenic drift

    PubMed Central

    Huang, Kuan-Ying A.; Rijal, Pramila; Schimanski, Lisa; Powell, Timothy J.; Lin, Tzou-Yien; McCauley, John W.; Daniels, Rodney S.; Townsend, Alain R.

    2015-01-01

    The selective pressure that drives antigenic changes in influenza viruses is thought to originate from the human immune response. Here, we have characterized the B cell repertoire from a previously vaccinated donor whose serum had reduced neutralizing activity against the recently evolved clade 6B H1N1pdm09 viruses. While the response was markedly polyclonal, 88% of clones failed to recognize clade 6B viruses; however, the ability to neutralize A/USSR/90/1977 influenza, to which the donor would have been exposed in childhood, was retained. In vitro selection of virus variants with representative monoclonal antibodies revealed that a single amino acid replacement at residue K163 in the Sa antigenic site, which is characteristic of the clade 6B viruses, was responsible for resistance to neutralization by multiple monoclonal antibodies and the donor serum. The K163 residue lies in a part of a conserved surface that is common to the hemagglutinins of the 1977 and 2009 H1N1 viruses. Vaccination with the 2009 hemagglutinin induced an antibody response tightly focused on this common surface that is capable of selecting current antigenic drift variants in H1N1pdm09 influenza viruses. Moreover, amino acid replacement at K163 was not highlighted by standard ferret antisera. Human monoclonal antibodies may be a useful adjunct to ferret antisera for detecting antigenic drift in influenza viruses. PMID:26011643

  8. Mammalian adaptation of influenza A(H7N9) virus is limited by a narrow genetic bottleneck

    PubMed Central

    Zaraket, Hassan; Baranovich, Tatiana; Kaplan, Bryan S.; Carter, Robert; Song, Min-Suk; Paulson, James C.; Rehg, Jerold E.; Bahl, Justin; Crumpton, Jeri C.; Seiler, Jon; Edmonson, Michael; Wu, Gang; Karlsson, Erik; Fabrizio, Thomas; Zhu, Huachen; Guan, Yi; Husain, Matloob; Schultz-Cherry, Stacey; Krauss, Scott; McBride, Ryan; Webster, Robert G.; Govorkova, Elena A.; Zhang, Jinghui; Russell, Charles J.; Webby, Richard J.

    2015-01-01

    Human infection with avian influenza A(H7N9) virus is associated mainly with the exposure to infected poultry. The factors that allow interspecies transmission but limit human-to-human transmission are unknown. Here we show that A/Anhui/1/2013(H7N9) influenza virus infection of chickens (natural hosts) is asymptomatic and that it generates a high genetic diversity. In contrast, diversity is tightly restricted in infected ferrets, limiting further adaptation to a fully transmissible form. Airborne transmission in ferrets is accompanied by the mutations in PB1, NP and NA genes that reduce viral polymerase and neuraminidase activity. Therefore, while A(H7N9) virus can infect mammals, further adaptation appears to incur a fitness cost. Our results reveal that a tight genetic bottleneck during avian-to-mammalian transmission is a limiting factor in A(H7N9) influenza virus adaptation to mammals. This previously unrecognized biological mechanism limiting species jumps provides a measure of adaptive potential and may serve as a risk assessment tool for pandemic preparedness. PMID:25850788

  9. Repeated threat (without harm) in a living environment potentiates defensive behavior.

    PubMed

    Kim, D J; Anderson, B J

    2015-02-15

    Children exposed to neighborhood violence have higher rates of aggression, but it is unclear whether aggression is associated with threat, harm or the combination of factors. All animals, including humans, experience threat as they leave the safety of home and risk harm to gather resources (foraging). To better understand how selective environmental variables drive behavioral tendencies, we developed a semi-naturalistic living environment that includes the need to navigate across space to obtain resources. Rats were housed for three weeks in two tub cages, one with food and the other with water, both consistently available, but separated by a 91 cm long tunnel. After habituating for three days, half the rats (threat stress condition) received unpredictable threats (simultaneous puff of air with ferret dander, abrupt flash of light, and an abrupt sound) when crossing the central position of the tunnel (random order with p=0.25) for 21 days. During the manipulation, the threat stress rats crossed the tunnel less and exhibited risk assessment behaviors. After cessation of the treatment conditions, the threat stress group spent more time burying a rag with ferret dander odor and was more likely to bury, and spent more time burying a highly novel stimulus. There were no group differences in symptoms of depression, avoidance, or exploration. The results suggest that repeated threats without harm increase pre-emptive defense behaviors, a form of active coping, without affecting passive forms of coping. PMID:25446759

  10. An immunohistochemical study of the middle ear muscles of some carnivores and primates, with special reference to the IIM and slow-tonic fibre types.

    PubMed Central

    Mascarello, F; Veggetti, A; Cerpenè, E; Rowlerson, A

    1983-01-01

    The middle ear muscles of several species of carnivores (cat, dog, fox, ferret and stone-marten) and some New World monkeys (Callithrix, Saimiri) and Old World monkeys (Cercopithecus, Macaca) were examined. The fibre type compositions of these muscles were determined by a combination of the standard histochemical myofibrillar ATPase method, and immunohistochemical techniques using myosintype-specific antisera. Immunohistochemically slow-tonic fibres were found in the stapedius muscles of only two carnivores, the ferret and stone-marten. In all the carnivores and the New World monkeys, tensor tympani muscle contained IIM, slow-tonic and slow-twitch fibres, but in the Old World monkeys it resembled stapedius muscle, and contained only Type I (slow-twitch) and IIA fibres. Thus, because all the species examined had IIM fibres in the jaw-closer muscles, this means that the common embryological origin of tensor tympani muscle and the jaw-closers does not necessarily result in tensor tympani muscle containing this fibre type even though IIM fibres occur only in first branchial arch muscles. This fact, together with other species differences in the fibre type composition of these muscles, shows that there is no typical composition of middle ear muscles in general, and suggests that the differences are related to very different functional requirements. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:6415024

  11. Comparative analysis of virulence of a novel, avian-origin H3N2 canine influenza virus in various host species.

    PubMed

    Lyoo, Kwang-Soo; Kim, Jeong-Ki; Kang, Bokyu; Moon, Hyoungjoon; Kim, Jongman; Song, Manki; Park, Bongkyun; Kim, Sang-Hyun; Webster, Robert G; Song, Daesub

    2015-01-01

    A novel avian-origin H3N2 canine influenza A virus (CIV) that showed high sequence similarities in hemagglutinin and neuraminidase genes with those of non-pathogenic avian influenza viruses was isolated in our routine surveillance program in South Korea. We previously reported that the pathogenicity of this strain could be reproduced in dogs and cats. In the present study, the host tropism of H3N2 CIV was examined by experimental inoculation into several host species, including chickens, pigs, mice, guinea pigs, and ferrets. The CIV infection resulted in no overt symptoms of disease in these host species. However, sero-conversion, virus shedding, and gross and histopathologic lung lesions were observed in guinea pig and ferrets but not in pigs, or mice. Based on the genetic similarity of our H3N2 CIV with currently circulating avian influenza viruses and the presence of α-2,3-linked rather than α-2,6-linked sialic acid receptors in the respiratory tract of dogs, we believed that this strain of CIV would have avian virus-like receptor specificity, but that seems to be contrary to our findings in the present study. Further studies are needed to determine the co-receptors of hemagglutinin or post-attachment factors related to virus internalization or pathogenesis in other animals.

  12. Polymerase discordance in novel swine influenza H3N2v constellations is tolerated in swine but not human respiratory epithelial cells.

    PubMed

    Powell, Joshua D; Dlugolenski, Daniel; Nagy, Tamas; Gabbard, Jon; Lee, Christopher; Tompkins, Stephen M; Tripp, Ralph A

    2014-01-01

    Swine-origin H3N2v, a variant of H3N2 influenza virus, is a concern for novel reassortment with circulating pandemic H1N1 influenza virus (H1N1pdm09) in swine because this can lead to the emergence of a novel pandemic virus. In this study, the reassortment prevalence of H3N2v with H1N1pdm09 was determined in swine cells. Reassortants evaluated showed that the H1N1pdm09 polymerase (PA) segment occurred within swine H3N2 with ∼ 80% frequency. The swine H3N2-human H1N1pdm09 PA reassortant (swH3N2-huPA) showed enhanced replication in swine cells, and was the dominant gene constellation. Ferrets infected with swH3N2-huPA had increased lung pathogenicity compared to parent viruses; however, swH3N2-huPA replication in normal human bronchoepithelial cells was attenuated - a feature linked to expression of IFN-β and IFN-λ genes in human but not swine cells. These findings indicate that emergence of novel H3N2v influenza constellations require more than changes in the viral polymerase complex to overcome barriers to cross-species transmission. Additionally, these findings reveal that while the ferret model is highly informative for influenza studies, slight differences in pathogenicity may not necessarily be indicative of human outcomes after infection.

  13. New England harbor seal H3N8 influenza virus retains avian-like receptor specificity

    PubMed Central

    Hussein, Islam T. M.; Krammer, Florian; Ma, Eric; Estrin, Michael; Viswanathan, Karthik; Stebbins, Nathan W.; Quinlan, Devin S.; Sasisekharan, Ram; Runstadler, Jonathan

    2016-01-01

    An influenza H3N8 virus, carrying mammalian adaptation mutations, was isolated from New England harbor seals in 2011. We sought to assess the risk of its human transmissibility using two complementary approaches. First, we tested the binding of recombinant hemagglutinin (HA) proteins of seal H3N8 and human-adapted H3N2 viruses to respiratory tissues of humans and ferrets. For human tissues, we observed strong tendency of the seal H3 to bind to lung alveoli, which was in direct contrast to the human-adapted H3 that bound mainly to the trachea. This staining pattern was also consistent in ferrets, the primary animal model for human influenza pathogenesis. Second, we compared the binding of the recombinant HAs to a library of 610 glycans. In contrast to the human H3, which bound almost exclusively to α-2,6 sialylated glycans, the seal H3 bound preferentially to α-2,3 sialylated glycans. Additionally, the seal H3N8 virus replicated in human lung carcinoma cells. Our data suggest that the seal H3N8 virus has retained its avian-like receptor binding specificity, but could potentially establish infection in human lungs. PMID:26888262

  14. The genome phylogeny of domestic cat, red panda and five mustelid species revealed by comparative chromosome painting and G-banding.

    PubMed

    Nie, Wenhui; Wang, Jinhuan; O'Brien, Patricia C M; Fu, Beiyuan; Ying, Tian; Ferguson-Smith, Malcolm A; Yang, Fengtang

    2002-01-01

    Genome-wide homology maps among stone marten (Martes foina, 2n = 38), domestic cat (Felis catus, 2n = 38), American mink (Mustela vison, 2n = 30), yellow-throated marten (Martes flavigula, 2n = 40), Old World badger (Meles meles, 2n = 44), ferret badger (Melogale moschata, 2n = 38) and red panda (Ailurus fulgens, 2n = 36) have been established by cross-species chromosome painting with a complete set of stone marten probes. In total, 18 stone marten autosomal probes reveal 20, 19, 21, 18 and 21 pairs of homologous chromosomal segments in the respective genomes of American mink, yellow-throated marten. Old World badger, ferret badger and red panda. Reciprocal painting between stone marten and cat delineated 21 pairs of homologous segments shared in both stone marten and cat genomes. The chromosomal painting results indicate that most chromosomes of these species are highly conserved and show one-to-one correspondence with stone marten and cat chromosomes or chromosomal arms, and that only a few interchromosomal rearrangements (Robertsonian fusions and fissions) have occurred during species radiation. By comparing the distribution patterns of conserved chromosomal segments in both these species and the putative ancestral carnivore karyotype, we have reconstructed the pathway of karyotype evolution of these species from the putative 2n = 42 ancestral carnivore karyotype. Our results support a close phylogenetic relationship between the red panda and mustelids. The homology data presented in these maps will allow us to transfer the cat gene mapping data to other unmapped carnivore species.

  15. New radiocarbon chronology of a late Holocene landslide event in the Mont Blanc massif, Italy

    NASA Astrophysics Data System (ADS)

    Hajdas, Irka; Sojc, Ursula; Ivy-Ochs, Susan; Akçar, Naki; Deline, Philip

    2016-04-01

    The Ferret valley Arp Nouva peat bog located in the Mont Blanc massif was critically evaluated since previously published radiocarbon dates have led to controversial conclusions on the formation of the swamp. Radiocarbon dating of roots from three pits of up to 1 m depth was applied to discuss the question whether the historical documented rock avalanche occurring in AD 1717 overran the peat bog or formed it at a later stage. Our results indicate that the rock avalanche formed the Arp Nouva peat bog by downstream blockage of the Bellecombe torrent. Furthermore, careful sample preparation with consequent separation of roots from the bulk peat sample provides possible explanation for the too old 14C ages of bulk peat samples dated previously (Deline and Kirkbride, 2009 and references therein). This work demonstrates that a combined geomorphological and geochronological approach is the most reliable way to reconstruct landscape evolution, especially in light of apparent chronological problems. The key to successful 14C dating is a careful sample selection and the identification of material that might be not ideal for chronological reconstructions. References Deline, Philip, and Martin P. Kirkbride. "Rock avalanches on a glacier and morainic complex in Haut Val Ferret (Mont Blanc Massif, Italy)".Geomorphology 103 (2009): 80-92.

  16. GLA-AF, an emulsion-free vaccine adjuvant for pandemic influenza.

    PubMed

    Clegg, Christopher H; Roque, Richard; Perrone, Lucy A; Rininger, Joseph A; Bowen, Richard; Reed, Steven G

    2014-01-01

    The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development. PMID:24551202

  17. Live, attenuated influenza virus (LAIV) vehicles are strong inducers of immunity toward influenza B virus

    PubMed Central

    Huber, Victor C.; Kleimeyer, Loren H.; McCullers, Jonathan A.

    2008-01-01

    Historically, vaccines developed toward influenza viruses of the B type using methodologies developed for influenza A viruses as a blueprint have not been equally efficacious or effective. Because most influenza research and public attention concerns influenza A viruses, these shortcomings have not been adequately addressed. In this manuscript, we utilized different influenza vaccine vehicles to compare immunogenicity and protection in mice and ferrets after vaccination against an influenza B virus. We report that plasmid DNA vaccines demonstrate low immunogenicity profiles and poor protection compared to either whole, inactivated influenza virus (IIV) or, live, attenuated influenza virus (LAIV) vaccines. When mixed prime:boost regimens using LAIV and IIV were studied, we observed a boosting effect in mice after priming with LAIV that was not seen when IIV was used as the prime. In ferrets LAIV induced high antibody titers after a single dose and provided a boost in IIV-primed animals. Regimens including LAIV as a prime demonstrated enhanced protection, and adjuvantation was required for efficacy using the IIV preparation. Our results differ from generally accepted influenza A virus vaccine models, and argue that strategies for control of influenza B virus should be considered separately from those for influenza A virus. PMID:18708106

  18. Reproduction and advances in reproductive studies in carnivores.

    PubMed

    Jewgenow, Katarina; Songsasen, Nucharin

    2014-01-01

    Reproductive mechanisms are extraordinarily diverse among species, even within the same phylogenetic clade. Due to this, it has been difficult to directly apply reproductive technologies developed in human and livestock to genetically manage ex situ wildlife, including carnivores. To date, more common, closely related species, e.g., domestic cats, dogs and ferrets have served as valuable models for developing reproductive technologies for managing rare, endangered carnivores. Artificial insemination and sperm cryopreservation have already been successfully used to manage ex situ populations in some carnivore species, such as the black-footed ferret, cheetah and giant panda. However, technologies aiming at preserving genetics of valuable females have not been fully developed in carnivores, due to the lack of fundamental knowledge about reproductive anatomy and physiology, gamete development, embryogenesis and cryopreservation. The present chapter is divided into two parts. The first part focuses on current knowledge about carnivore reproduction, with emphasis on species diversity in reproductive mechanisms. The second part highlights the progress in reproductive science and related technologies made during the last decade. In addition, we provide examples of how reproductive technologies can contribute to carnivore management and conservation. Although carnivores are comprised of 19 families, we will only focus our attention on four taxonomic groups, including felids, canids, ursids and mustelids. PMID:25091912

  19. Focused antibody response to influenza linked to antigenic drift.

    PubMed

    Huang, Kuan-Ying A; Rijal, Pramila; Schimanski, Lisa; Powell, Timothy J; Lin, Tzou-Yien; McCauley, John W; Daniels, Rodney S; Townsend, Alain R

    2015-07-01

    The selective pressure that drives antigenic changes in influenza viruses is thought to originate from the human immune response. Here, we have characterized the B cell repertoire from a previously vaccinated donor whose serum had reduced neutralizing activity against the recently evolved clade 6B H1N1pdm09 viruses. While the response was markedly polyclonal, 88% of clones failed to recognize clade 6B viruses; however, the ability to neutralize A/USSR/90/1977 influenza, to which the donor would have been exposed in childhood, was retained. In vitro selection of virus variants with representative monoclonal antibodies revealed that a single amino acid replacement at residue K163 in the Sa antigenic site, which is characteristic of the clade 6B viruses, was responsible for resistance to neutralization by multiple monoclonal antibodies and the donor serum. The K163 residue lies in a part of a conserved surface that is common to the hemagglutinins of the 1977 and 2009 H1N1 viruses. Vaccination with the 2009 hemagglutinin induced an antibody response tightly focused on this common surface that is capable of selecting current antigenic drift variants in H1N1pdm09 influenza viruses. Moreover, amino acid replacement at K163 was not highlighted by standard ferret antisera. Human monoclonal antibodies may be a useful adjunct to ferret antisera for detecting antigenic drift in influenza viruses. PMID:26011643

  20. Recovery of cortical binocularity and orientation selectivity after the critical period for ocular dominance plasticity.

    PubMed

    Liao, David S; Krahe, Thomas E; Prusky, Glen T; Medina, Alexandre E; Ramoa, Ary S

    2004-10-01

    Cortical binocularity is abolished by monocular deprivation (MD) during a critical period of development lasting from approximately postnatal day (P) 35 to P70 in ferrets. Although this is one of the best-characterized models of neural plasticity and amblyopia, very few studies have examined the requirements for recovery of cortical binocularity and orientation selectivity of deprived eye responses. Recent studies indicating that different mechanisms regulate loss and recovery of binocularity raise the possibility that different sensitive periods characterize loss and recovery of deprived eye responses. In this report, we have examined whether the potential for recovery of binocularity and orientation selectivity is restricted to the critical period. Quantitative single unit recordings revealed recovery of cortical binocularity and full recovery of orientation selectivity of deprived eye responses following prolonged periods of MD (i.e., >3 wk) starting at P49, near the peak of plasticity. Surprisingly, recovery was present when binocular vision was restored after the end of the critical period for ocular dominance plasticity, as late as P83. In contrast, ferrets that had never received visual experience through the deprived eye failed to recover binocularity even though normal binocular vision was restored at P50, halfway through the critical period. Collectively, these results indicate that there is potential for recovery of cortical binocularity and deprived eye orientation selectivity after the end of the critical period for ocular dominance plasticity.

  1. Comparison of ranging behaviour in a multi-species complex of free-ranging hosts of bovine tuberculosis in relation to their use as disease sentinels.

    PubMed

    Yockney, I J; Nugent, G; Latham, M C; Perry, M; Cross, M L; Byrom, A E

    2013-07-01

    Sentinel species are increasingly used by disease managers to detect and monitor the prevalence of zoonotic diseases in wildlife populations. Characterizing home-range movements of sentinel hosts is thus important for developing improved disease surveillance methods, especially in systems where multiple host species co-exist. We studied ranging activity of major hosts of bovine tuberculosis (TB) in an upland habitat of New Zealand: we compared home-range coverage by ferrets (Mustela furo), wild deer (Cervus elaphus), feral pigs (Sus scrofa), brushtail possums (Trichosurus vulpecula) and free-ranging farmed cattle (Bos taurus). We also report in detail the proportional utilization of a seasonal (4-monthly) range area for the latter four species. Possums covered the smallest home range (<30 ha), ferrets covered ~100 ha, pigs ~4 km(2), deer and cattle both >30 km2. For any given weekly period, cattle, deer and pigs were shown to utilize 37–45% of their estimated 4-month range, while possums utilized 62% during any weekly period and 85% during any monthly period of their estimated 4-month range. We suggest that present means for estimating TB detection kernels, based on long-term range size estimates for possums and sentinel species, probably overstate the true local surveillance coverage per individual. PMID:23433406

  2. Delayed implantation in mustelids, with special emphasis on the spotted skunk.

    PubMed

    Mead, R A

    1981-01-01

    Three distinct reproductive patterns are exhibited by mustelids. Some species (ferret and least weasel) breed during spring and summer and do not exhibit delayed implantation. Others (mink and striped skunk) exhibit variable gestation periods with brief periods of delayed implantation occurring only if the females are mated early in the season. Most mustelids (western spotted skunk, badgers, marten, wolverine, etc.) always exhibit a prolonged period of delayed implantation lasting several months. In such species, the luteal cells fail to undergo complete differentiation during the prolonged period of embryonic diapause. The process of luteal differentiation, which involves doubling of luteal cell size, extensive production of smooth endoplasmic reticulum, and mitochondrial changes, and which is accompanied by increased progesterone secretion, occurs a few days before implantation and coincides with renewed embryonic development. Attempts to induce implantation in mustelids by injecting progesterone have failed, suggesting that other ovarian hormones hormones are required to induce nidation. Changes in photoperiod will hasten or delay luteal development, progesterone secretion and implantation. Hypophysectomy before the time of increased luteal function prevents implantation and increased progesterone secretion, whereas hysterectomy has no effect on progesterone secretion. This indicates that only pituitary hormones are required to induce the final steps in luteal cell differentiation and progesterone secretion. Attempts to induce increased luteal function and implantation by administration of exogenous gonadotrophic hormones have been inconclusive. Prolactin may be important in regulating luteal function in mink and ferrets but may be less significant in other mustelids such as the spotted skunk and European badger.

  3. Reproduction and advances in reproductive studies in carnivores.

    PubMed

    Jewgenow, Katarina; Songsasen, Nucharin

    2014-01-01

    Reproductive mechanisms are extraordinarily diverse among species, even within the same phylogenetic clade. Due to this, it has been difficult to directly apply reproductive technologies developed in human and livestock to genetically manage ex situ wildlife, including carnivores. To date, more common, closely related species, e.g., domestic cats, dogs and ferrets have served as valuable models for developing reproductive technologies for managing rare, endangered carnivores. Artificial insemination and sperm cryopreservation have already been successfully used to manage ex situ populations in some carnivore species, such as the black-footed ferret, cheetah and giant panda. However, technologies aiming at preserving genetics of valuable females have not been fully developed in carnivores, due to the lack of fundamental knowledge about reproductive anatomy and physiology, gamete development, embryogenesis and cryopreservation. The present chapter is divided into two parts. The first part focuses on current knowledge about carnivore reproduction, with emphasis on species diversity in reproductive mechanisms. The second part highlights the progress in reproductive science and related technologies made during the last decade. In addition, we provide examples of how reproductive technologies can contribute to carnivore management and conservation. Although carnivores are comprised of 19 families, we will only focus our attention on four taxonomic groups, including felids, canids, ursids and mustelids.

  4. Focused antibody response to influenza linked to antigenic drift.

    PubMed

    Huang, Kuan-Ying A; Rijal, Pramila; Schimanski, Lisa; Powell, Timothy J; Lin, Tzou-Yien; McCauley, John W; Daniels, Rodney S; Townsend, Alain R

    2015-07-01

    The selective pressure that drives antigenic changes in influenza viruses is thought to originate from the human immune response. Here, we have characterized the B cell repertoire from a previously vaccinated donor whose serum had reduced neutralizing activity against the recently evolved clade 6B H1N1pdm09 viruses. While the response was markedly polyclonal, 88% of clones failed to recognize clade 6B viruses; however, the ability to neutralize A/USSR/90/1977 influenza, to which the donor would have been exposed in childhood, was retained. In vitro selection of virus variants with representative monoclonal antibodies revealed that a single amino acid replacement at residue K163 in the Sa antigenic site, which is characteristic of the clade 6B viruses, was responsible for resistance to neutralization by multiple monoclonal antibodies and the donor serum. The K163 residue lies in a part of a conserved surface that is common to the hemagglutinins of the 1977 and 2009 H1N1 viruses. Vaccination with the 2009 hemagglutinin induced an antibody response tightly focused on this common surface that is capable of selecting current antigenic drift variants in H1N1pdm09 influenza viruses. Moreover, amino acid replacement at K163 was not highlighted by standard ferret antisera. Human monoclonal antibodies may be a useful adjunct to ferret antisera for detecting antigenic drift in influenza viruses.

  5. Host Species Restriction of Middle East Respiratory Syndrome Coronavirus through Its Receptor, Dipeptidyl Peptidase 4

    PubMed Central

    van Doremalen, Neeltje; Miazgowicz, Kerri L.; Milne-Price, Shauna; Bushmaker, Trenton; Robertson, Shelly; Scott, Dana; Kinne, Joerg; McLellan, Jason S.; Zhu, Jiang

    2014-01-01

    ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir. IMPORTANCE The ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 701 laboratory-confirmed cases to date, with 249 fatalities. Although bats and dromedary camels have been identified as potential MERS-CoV hosts, the virus has so far not been isolated from any species

  6. Development of a high-yield reassortant influenza vaccine virus derived from the A/Anhui/1/2013 (H7N9) strain.

    PubMed

    Nakamura, Kazuya; Shirakura, Masayuki; Suzuki, Yasushi; Naito, Tadasuke; Fujisaki, Seiichiro; Tashiro, Masato; Nobusawa, Eri

    2016-01-12

    In April 2013, the first three fatal cases of human infection with an avian influenza A virus (H7N9) were reported in China. Because of a pandemic threat by this virus, we have commenced to develop candidate vaccine viruses (CVVs). Three 6:2 genetic reassortant viruses with different hemagglutinin (HA) sequences, NIIDRG-10, -10.1 and -10.2, were generated by a reverse genetics technique between the high egg-growth master virus, A/Puerto Rico/8/34 (H1N1) and A/Anhui/1/2013 (H7N9), kindly provided by the Chinese Center for Disease Control and Prevention. The different HA gene sequences of the three CVVs were derived from the original virus stock. NIIDRG-10 possesses HA, whose sequence is identical to that of the original A/Anhui/1/2013 (H7N9) in the Global Initiative on Sharing Avian Influenza Data (EPI439507), while NIIDRG-10.1 and -10.2 possess amino acid differences, A125T and N123D/N149D, respectively, compared with NIIDRG-10. NIIDRG-10 replicated in embryonated chicken eggs with low hemagglutination titer 128, whereas NIIDRG-10.1 and -10.2 grew well with hemagglutination titer 1024. These viruses reacted well with a ferret antiserum raised against the original A/Anhui/1/2013 virus. Ferret antiserum against NIIDRG-10.1 reacted well with A/Anhui/1/2013 similar to the homologous virus NIIDRG-10.1. These results indicated that NIIDRG-10.1 passed the two-way test of antigenic identity. In contrast, the ferret antiserum against NIIDRG-10.2 reacted with A/Anhui/1/2013 at an 8-fold lower hemagglutination inhibition titer than with the homologous virus NIIDRG-10.2, indicating an antigenic change. The total and HA protein yields of NIIDRG-10.1 were 14.7 and 6.9 μg/ml, respectively, similar to those levels of high-yield seed viruses of seasonal influenza vaccines. NIIDRG-10.1 was approved as one of the CVVs for H7N9 viruses by the WHO in 2013. The candidate vaccine derived from NIIDRG-10.1 is currently being evaluated in a phase II clinical study in Japan. PMID:26657023

  7. Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein

    PubMed Central

    Russier, Marion; Yang, Guohua; Rehg, Jerold E.; Wong, Sook-San; Mostafa, Heba H.; Barman, Subrata; Krauss, Scott; Webster, Robert G.; Webby, Richard J.; Russell, Charles J.

    2016-01-01

    Influenza pandemics require that a virus containing a hemagglutinin (HA) surface antigen previously unseen by a majority of the population becomes airborne-transmissible between humans. Although the HA protein is central to the emergence of a pandemic influenza virus, its required molecular properties for sustained transmission between humans are poorly defined. During virus entry, the HA protein binds receptors and is triggered by low pH in the endosome to cause membrane fusion; during egress, HA contributes to virus assembly and morphology. In 2009, a swine influenza virus (pH1N1) jumped to humans and spread globally. Here we link the pandemic potential of pH1N1 to its HA acid stability, or the pH at which this one-time-use nanomachine is either triggered to cause fusion or becomes inactivated in the absence of a target membrane. In surveillance isolates, our data show HA activation pH values decreased during the evolution of H1N1 from precursors in swine (pH 5.5–6.0), to early 2009 human cases (pH 5.5), and then to later human isolates (pH 5.2–5.4). A loss-of-function pH1N1 virus with a destabilizing HA1-Y17H mutation (pH 6.0) was less pathogenic in mice and ferrets, less transmissible by contact, and no longer airborne-transmissible. A ferret-adapted revertant (HA1-H17Y/HA2-R106K) regained airborne transmissibility by stabilizing HA to an activation pH of 5.3, similar to that of human-adapted isolates from late 2009–2014. Overall, these studies reveal that a stable HA (activation pH ≤ 5.5) is necessary for pH1N1 influenza virus pathogenicity and airborne transmissibility in ferrets and is associated with pandemic potential in humans. PMID:26811446

  8. Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein.

    PubMed

    Russier, Marion; Yang, Guohua; Rehg, Jerold E; Wong, Sook-San; Mostafa, Heba H; Fabrizio, Thomas P; Barman, Subrata; Krauss, Scott; Webster, Robert G; Webby, Richard J; Russell, Charles J

    2016-02-01

    Influenza pandemics require that a virus containing a hemagglutinin (HA) surface antigen previously unseen by a majority of the population becomes airborne-transmissible between humans. Although the HA protein is central to the emergence of a pandemic influenza virus, its required molecular properties for sustained transmission between humans are poorly defined. During virus entry, the HA protein binds receptors and is triggered by low pH in the endosome to cause membrane fusion; during egress, HA contributes to virus assembly and morphology. In 2009, a swine influenza virus (pH1N1) jumped to humans and spread globally. Here we link the pandemic potential of pH1N1 to its HA acid stability, or the pH at which this one-time-use nanomachine is either triggered to cause fusion or becomes inactivated in the absence of a target membrane. In surveillance isolates, our data show HA activation pH values decreased during the evolution of H1N1 from precursors in swine (pH 5.5-6.0), to early 2009 human cases (pH 5.5), and then to later human isolates (pH 5.2-5.4). A loss-of-function pH1N1 virus with a destabilizing HA1-Y17H mutation (pH 6.0) was less pathogenic in mice and ferrets, less transmissible by contact, and no longer airborne-transmissible. A ferret-adapted revertant (HA1-H17Y/HA2-R106K) regained airborne transmissibility by stabilizing HA to an activation pH of 5.3, similar to that of human-adapted isolates from late 2009-2014. Overall, these studies reveal that a stable HA (activation pH ≤ 5.5) is necessary for pH1N1 influenza virus pathogenicity and airborne transmissibility in ferrets and is associated with pandemic potential in humans. PMID:26811446

  9. Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells.

    PubMed

    Nowakowski, Tomasz J; Pollen, Alex A; Di Lullo, Elizabeth; Sandoval-Espinosa, Carmen; Bershteyn, Marina; Kriegstein, Arnold R

    2016-05-01

    The recent outbreak of Zika virus (ZIKV) in Brazil has been linked to substantial increases in fetal abnormalities and microcephaly. However, information about the underlying molecular and cellular mechanisms connecting viral infection to these defects remains limited. In this study we have examined the expression of receptors implicated in cell entry of several enveloped viruses including ZIKV across diverse cell types in the developing brain. Using single-cell RNA-seq and immunohistochemistry, we found that the candidate viral entry receptor AXL is highly expressed by human radial glial cells, astrocytes, endothelial cells, and microglia in developing human cortex and by progenitor cells in developing retina. We also show that AXL expression in radial glia is conserved in developing mouse and ferret cortex and in human stem cell-derived cerebral organoids, highlighting multiple experimental systems that could be applied to study mechanisms of ZIKV infectivity and effects on brain development.

  10. IRS targets abusive oil and gas and other tax-shelter investments as litigating vehicles

    SciTech Connect

    Carter, R.D.; Parrott, T.G.

    1980-12-01

    The Internal Revenue Service (IRS) has targeted all investors and promoters involved in tax-sheltered investments for audit. Several new audit types and procedures will mean that investors are more likely to be audited and, when they are, it will take longer and cost more. Oil- and gas-drilling funds are among those targeted for audits in an effort to ferret out tax-shelter abuses. One danger of a new fast-track rulings section in the Rulings Division of the IRS is that an erroneous ruling issued might ultimately be resolved in the tax payer's favor in court; nevertheless, the promotor may be precluded from raising funds from discouraged investors who could have been afforded legitimate tax shelters. Probably the greatest potential area for abuse is each IRS district having sole jurisdiction to determine what is a litigating vehicle case.

  11. Sensory experience modifies feature map relationships in visual cortex

    PubMed Central

    Cloherty, Shaun L; Hughes, Nicholas J; Hietanen, Markus A; Bhagavatula, Partha S

    2016-01-01

    The extent to which brain structure is influenced by sensory input during development is a critical but controversial question. A paradigmatic system for studying this is the mammalian visual cortex. Maps of orientation preference (OP) and ocular dominance (OD) in the primary visual cortex of ferrets, cats and monkeys can be individually changed by altered visual input. However, the spatial relationship between OP and OD maps has appeared immutable. Using a computational model we predicted that biasing the visual input to orthogonal orientation in the two eyes should cause a shift of OP pinwheels towards the border of OD columns. We then confirmed this prediction by rearing cats wearing orthogonally oriented cylindrical lenses over each eye. Thus, the spatial relationship between OP and OD maps can be modified by visual experience, revealing a previously unknown degree of brain plasticity in response to sensory input. DOI: http://dx.doi.org/10.7554/eLife.13911.001 PMID:27310531

  12. Rat bite fever, a fatal case of Streptobacillus moniliformis infection in a 14-month-old boy.

    PubMed

    Banerjee, Priya; Ali, Zabiullah; Fowler, David R

    2011-03-01

    Streptobacillus moniliformis is the primary cause of rat bite fever in North America. Children under 12 years of age are primarily infected, presenting with an acute syndrome of fever, rash, and polyarthritis. Common vectors include rats and mice. Transmission is predominantly from a bite or scratch, but contact with or ingestion of food contaminated with feces or saliva has also been reported. We report a fatal case of S. moniliformis infection in a 14-month-old-boy. At home, the child was exposed to filthy living conditions and the family had pet ferrets. Autopsy revealed a red-pink, mostly confluent rash and a circumscribed area suspicious for a possible bite mark. Cerebrospinal fluid cultures were positive for S. moniliformis. This case highlighted key features, such as the morbiliform rash, but lacked lymphadenopathy or joint manifestations. It is important to consider rat or rodent exposure as a source of infection.

  13. Animal models for influenza virus transmission studies: A historical perspective

    PubMed Central

    Bouvier, Nicole M.

    2015-01-01

    Animal models are used to simulate, under experimental conditions, the complex interactions among host, virus, and environment that affect the person-to-person spread of influenza viruses. The three species that have been most frequently employed, both past and present, as influenza virus transmission models -- ferrets, mice, and guinea pigs -- have each provided unique insights into the factors governing the efficiency with which these viruses pass from an infected host to a susceptible one. This review will highlight a few of these noteworthy discoveries, with a particular focus on the historical contexts in which each model was developed and the advantages and disadvantages of each species with regard to the study of influenza virus transmission among mammals. PMID:26126082

  14. Access to microdata on the Internet: Web-based analysis and data subset extraction tools.

    PubMed

    Chung, Kyusuk; Mullner, Ross; Yang, Duckhye

    2002-12-01

    The Internet is increasingly being recognized as an invaluable component of education. At the college and university level, online databases and statistical tools for Web-based analysis and data subset extraction have become important instructional resources. These Internet resources enable students to formulate specific research hypotheses, identify relevant variables, and analyze large existing databases. This article describes three of these resources: the Federal Electronic Research and Review Extraction Tool (FERRET) of the U.S. Bureau of the Census, the Survey Documentation and Analysis (SDA) unit at the University of California, Berkley, and the Inter-University Consortium for Political and Social Research (ICPSR), which is housed at the University of Michigan. PMID:12385537

  15. Genome Sequence of a Clinical Isolate of Campylobacter jejuni from Thailand▿ †

    PubMed Central

    Poly, Frédéric; Read, Timothy; Tribble, David R.; Baqar, Shahida; Lorenzo, Maria; Guerry, Patricia

    2007-01-01

    Campylobacter jejuni CG8486, which belongs to the HS4 complex, was isolated from a patient with inflammatory diarrhea in Thailand. This strain caused a diarrheal disease in ferrets comparable to that caused by C. jejuni strain 81-176, but it was much less invasive for epithelial cells in vitro than 81-176. Complete genome sequencing of CG8486 revealed a 1.65-Mb genome that was very similar to the other two published genomes of clinical isolates of C. jejuni, the genomes of 81-176 and NCTC 11168, with a limited number of CG8486-specific genes mapping outside the hypervariable carbohydrate biosynthesis loci. These data suggest that the genes required for induction of inflammatory diarrhea are among the genes shared by CG8486 and 81-176 but that either major changes in the carbohydrate loci and/or more subtle changes in other genes may modulate virulence. PMID:17438034

  16. Influenza virus vaccine for neglected hosts: horses and dogs

    PubMed Central

    2016-01-01

    This study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. Canine influenza is a virus of equine or avian origin and infects companion animals that live in close contact with humans; this results in possible exposure to the seasonal epizootic influenza virus. There have been case reports of genetic reassortment between human and canine influenza viruses, which results in high virulence and the ability of transmission to ferrets. This emphasizes the need for vaccine research on neglected hosts to update knowledge on current strains and to advance technology for controlling influenza outbreaks for public health. PMID:27489801

  17. The what, why, and how of born-open data.

    PubMed

    Rouder, Jeffrey N

    2016-09-01

    Although many researchers agree that scientific data should be open to scrutiny to ferret out poor analyses and outright fraud, most raw data sets are not available on demand. There are many reasons researchers do not open their data, and one is technical. It is often time consuming to prepare and archive data. In response, my laboratory has automated the process such that our data are archived the night they are created without any human approval or action. All data are versioned, logged, time stamped, and uploaded including aborted runs and data from pilot subjects. The archive is GitHub, github.com, the world's largest collection of open-source materials. Data archived in this manner are called born open. In this paper, I discuss the benefits of born-open data and provide a brief technical overview of the process. I also address some of the common concerns about opening data before publication.

  18. The Controlled Cortical Impact Model of Experimental Brain Trauma: Overview, Research Applications, and Protocol.

    PubMed

    Osier, Nicole; Dixon, C Edward

    2016-01-01

    Controlled cortical impact (CCI) is a commonly used and highly regarded model of brain trauma that uses a pneumatically or electromagnetically controlled piston to induce reproducible and well-controlled injury. The CCI model was originally used in ferrets and it has since been scaled for use in many other species. This chapter will describe the historical development of the CCI model, compare and contrast the pneumatic and electromagnetic models, and summarize key short- and long-term consequences of TBI that have been gleaned using this model. In accordance with the recent efforts to promote high-quality evidence through the reporting of common data elements (CDEs), relevant study details-that should be reported in CCI studies-will be noted. PMID:27604719

  19. Evaluation of the toxic properties of naturally weathered Exxon Valdez crude oil to surrogate wildlife species

    SciTech Connect

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Prince, H.H.; Ringer, R.K.

    1995-12-31

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) to avian and mammalian wildlife species were evaluated using the surrogate species, mallard duck, Anas platyrhynchos, and European ferret, Mustela putorius. This study was conducted to evaluate the potential for toxic (rather than physical) injury to wildlife species that may have been exposed to WEVC, either through external contact or through dietary uptake. Previous studies have assessed the toxicity of unweathered crude oils, including Alaska North Slope Crude, but little information exists regarding the toxicity of a naturally weathered crude oil, typical of that encountered following a spill. A battery of laboratory toxicity tests was conducted, in compliance with standard and published test procedures, to evaluate acute and subchronic toxicity of WEVC. These included tests of food avoidance, reproductive effects, and direct eggshell application toxicity. Naturally weathered EVC, recovered postspill from Prince William Sound, was used as the test material. 36 refs., 7 figs., 4 tabs.

  20. Sensory experience modifies feature map relationships in visual cortex.

    PubMed

    Cloherty, Shaun L; Hughes, Nicholas J; Hietanen, Markus A; Bhagavatula, Partha S; Goodhill, Geoffrey J; Ibbotson, Michael R

    2016-01-01

    The extent to which brain structure is influenced by sensory input during development is a critical but controversial question. A paradigmatic system for studying this is the mammalian visual cortex. Maps of orientation preference (OP) and ocular dominance (OD) in the primary visual cortex of ferrets, cats and monkeys can be individually changed by altered visual input. However, the spatial relationship between OP and OD maps has appeared immutable. Using a computational model we predicted that biasing the visual input to orthogonal orientation in the two eyes should cause a shift of OP pinwheels towards the border of OD columns. We then confirmed this prediction by rearing cats wearing orthogonally oriented cylindrical lenses over each eye. Thus, the spatial relationship between OP and OD maps can be modified by visual experience, revealing a previously unknown degree of brain plasticity in response to sensory input. PMID:27310531

  1. Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus

    PubMed Central

    Yoon, Sun-Woo; Chen, Noam; Ducatez, Mariette F.; McBride, Ryan; Barman, Subrata; Fabrizio, Thomas P.; Webster, Robert G.; Haliloglu, Turkan; Paulson, James C.; Russell, Charles J.; Hertz, Tomer; Ben-Tal, Nir; Webby, Richard J.

    2015-01-01

    The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. While it has been shown that acquisition of the neuraminidase (NA) and matrix (M) gene segments from a Eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09), we show here that an arginine to lysine change in the hemagglutinin (HA) was also necessary. This change at position 149 was distal to the receptor binding site but affected virus-receptor affinity and HA dynamics, allowing the virus to replicate more efficiently in nasal turbinate epithelium and subsequently transmit between ferrets. Receptor affinity should be considered as a factor limiting swine virus spread in humans. PMID:26269288

  2. Spread of Influenza Virus A (H5N1) Clade 2.3.2.1 to Bulgaria in Common Buzzards

    PubMed Central

    Marinova-Petkova, Atanaska; Georgiev, Georgi; Seiler, Patrick; Darnell, Daniel; Franks, John; Krauss, Scott; Webby, Richard J.

    2012-01-01

    On March 15, 2010, a highly pathogenic avian influenza virus was isolated from the carcass of a common buzzard (Buteo buteo) in Bulgaria. Phylogenetic analyses of the virus showed a close genetic relationship with influenza virus A (H5N1) clade 2.3.2.1 viruses isolated from wild birds in the Tyva Republic and Mongolia during 2009–2010. Designated A/common buzzard/Bulgaria/38WB/2010, this strain was highly pathogenic in chickens but had low pathogenicity in mice and ferrets and no molecular markers of increased pathogenicity in mammals. The establishment of clade 2.3.2.1 highly pathogenic avian influenza viruses of the H5N1 subtype in wild birds in Europe would increase the likelihood of health threats to humans and poultry in the region. PMID:23017273

  3. Influenza virus vaccine for neglected hosts: horses and dogs.

    PubMed

    Na, Woonsung; Yeom, Minjoo; Yuk, Huijoon; Moon, Hyoungjoon; Kang, Bokyu; Song, Daesub

    2016-07-01

    This study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. Canine influenza is a virus of equine or avian origin and infects companion animals that live in close contact with humans; this results in possible exposure to the seasonal epizootic influenza virus. There have been case reports of genetic reassortment between human and canine influenza viruses, which results in high virulence and the ability of transmission to ferrets. This emphasizes the need for vaccine research on neglected hosts to update knowledge on current strains and to advance technology for controlling influenza outbreaks for public health.

  4. [Research Advances in the Porcine Deltacoronavirus].

    PubMed

    Fang, Puxian; Fang, Liurong; Dong, Nan; Xiao, Shaobo

    2016-03-01

    The deltacoronavirus is a new member of the subfamily Coronaviridae of the family Coronaviridae. Deltacoronaviruses can infect birds and mammals. Deltacoronaviruses were detected in early 2007 in Asian leopard cats and Chinese ferret badgers. In 2014, porcine deltacoronavirus (PDCoV) infection spread rapidly in the USA. Moreover, cell culture-adapted PDCoV has been obtained from infected piglets. Animal experiments have confirmed that the isolated PDCoV is highly pathogenic and causes severe diarrhea in piglets. Thus, the PDCoV can be considered to be a good model to study the deltacoronavirus. In this review, we discuss the etiology, epidemiology, pathogenicity, culture, and diagnostic methods of the PDCoV. PMID:27396171

  5. Animal models for influenza virus pathogenesis, transmission, and immunology

    PubMed Central

    Thangavel, Rajagowthamee R.; Bouvier, Nicole M.

    2014-01-01

    In humans, infection with an influenza A or B virus manifests typically as an acute and self-limited upper respiratory tract illness characterized by fever, cough, sore throat, and malaise. However, influenza can present along a broad spectrum of disease, ranging from sub-clinical or even asymptomatic infection to a severe primary viral pneumonia requiring advanced medical supportive care. Disease severity depends upon the virulence of the influenza virus strain and the immune competence and previous influenza exposures of the patient. Animal models are used in influenza research not only to elucidate the viral and host factors that affect influenza disease outcomes in and spread among susceptible hosts, but also to evaluate interventions designed to prevent or reduce influenza morbidity and mortality in man. This review will focus on the three animal models currently used most frequently in influenza virus research -- mice, ferrets, and guinea pigs -- and discuss the advantages and disadvantages of each. PMID:24709389

  6. Influenza (H5N1) viruses in poultry, Russian Federation, 2005-2006.

    PubMed

    Lipatov, Aleksandr S; Evseenko, Vasily A; Yen, Hui-Ling; Zaykovskaya, Anna V; Durimanov, Alexander G; Zolotykh, Sergey I; Netesov, Sergey V; Drozdov, Ilya G; Onishchenko, Gennadiy G; Webster, Robert G; Shestopalov, Alexander M

    2007-04-01

    We studied 7 influenza (H5N1) viruses isolated from poultry in western Siberia and the European part of the Russian Federation during July 2005-February 2006. Full genome sequences showed high homology to Qinghai-like influenza (H5N1) viruses. Phylogenetic analysis not only showed a close genetic relationship between the H5N1 strains isolated from poultry and wild migratory waterfowls but also suggested genetic reassortment among the analyzed isolates. Analysis of deduced amino acid sequences of the M2 and neuraminidase proteins showed that all isolates are potentially sensitive to currently available antiviral drugs. Pathogenicity testing showed that all studied viruses were highly pathogenic in chickens; for 3 isolates tested in mice and 2 tested in ferrets, pathogenicity was heterogeneous. Pathogenicity in mammalian models was generally correlated with Lys at residue 627 of polymerase basic protein 2.

  7. Animal Models of Cystic Fibrosis Pathology: Phenotypic Parallels and Divergences.

    PubMed

    Lavelle, Gillian M; White, Michelle M; Browne, Niall; McElvaney, Noel G; Reeves, Emer P

    2016-01-01

    Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The resultant characteristic ion transport defect results in decreased mucociliary clearance, bacterial colonisation, and chronic neutrophil-dominated inflammation. Much knowledge surrounding the pathophysiology of the disease has been gained through the generation of animal models, despite inherent limitations in each. The failure of certain mouse models to recapitulate the phenotypic manifestations of human disease has initiated the generation of larger animals in which to study CF, including the pig and the ferret. This review will summarise the basic phenotypes of three animal models and describe the contributions of such animal studies to our current understanding of CF. PMID:27340661

  8. Endogenous Lentiviral Elements in the Weasel Family (Mustelidae)

    PubMed Central

    Han, Guan-Zhu; Worobey, Michael

    2012-01-01

    Endogenous retroviruses provide molecular fossils for studying the ancient evolutionary history of retroviruses. Here, we report our independent discovery and analysis of endogenous lentiviral insertions (Mustelidae endogenous lentivirus [MELV]) within the genomes of weasel family (Mustelidae). Genome-scale screening identified MELV elements in the domestic ferret (Mustela putorius furo) genome (MELVmpf). MELVmpf exhibits a typical lentiviral genomic organization. Phylogenetic analyses position MELVmpf basal to either primate lentiviruses or feline immunodeficiency virus. Moreover, we verified the presence of MELV insertions in the genomes of several species of the Lutrinae and Mustelinae subfamilies but not the Martinae subfamily, suggesting that the invasion of MELV into the Mustelidae genomes likely took place between 8.8 and 11.8 Ma. The discovery of MELV in weasel genomes extends the host range of lentiviruses to the Caniformia (order Carnivora) and provides important insights into the prehistoric diversity of lentiviruses. PMID:22522310

  9. An update on feline infectious peritonitis: diagnostics and therapeutics.

    PubMed

    Pedersen, Niels C

    2014-08-01

    This review is concerned with what has been learned about feline infectious peritonitis (FIP) diagnostics and therapeutics since the publication of an extensive overview of literature covering the period 1963-2009. Although progress has been made in both areas, obtaining a definitive diagnosis of FIP remains a problem for those veterinarians and/or cat owners who require absolute certainty. This review will cover both indirect and direct diagnostic tests for the disease and will emphasize their limitations, as well as their specificity and sensitivity. There is still no effective treatment for FIP, although there are both claims that such therapies exist and glimmers of hope coming from new therapies that are under research. FIP has also been identified in wild felids and FIP-like disease is now a growing problem among pet ferrets.

  10. Evaluation of an attenuated, cold-recombinant influenza B virus vaccine.

    PubMed

    Monto, A S; Miller, F D; Maassab, H F

    1982-01-01

    A live, attenuated influenza B virus vaccine was evaluated in a group of students. The virus, cold-recombinant (CR) 7, was produced by recombining the attenuated cold-adapted parent, B/Ann Arbor/1/66, with a wild strain, B/Hong Kong/8/73. In ferrets, the wild strain produced histopathologic lesions in the lungs, whereas the CR strain and the attenuated parent did not. A total of 306 individuals was inoculated intranasally with either the CR virus or a placebo. After inoculation, only one symptom was significantly more common in the vaccinees than in the control subjects. That symptom, sore throat, occurred briefly in 26% of the vaccine recipients and in 10.5% of the placebo recipients. An outbreak of influenza B occurred three months after vaccination. When serologic infection rates in the two groups were compared, it was found that the vaccine had been significantly effective (P less than 0.01) in preventing infection.

  11. The immunomodulating V and W proteins of Nipah virus determine disease course

    PubMed Central

    Satterfield, Benjamin A.; Cross, Robert W.; Fenton, Karla A.; Agans, Krystle N.; Basler, Christopher F.; Geisbert, Thomas W.; Mire, Chad E.

    2015-01-01

    The viral determinants that contribute to Nipah virus (NiV)-mediated disease are poorly understood compared with other paramyxoviruses. Here we use recombinant NiVs (rNiVs) to examine the contributions of the NiV V and W proteins to NiV pathogenesis in a ferret model. We show that a V-deficient rNiV is susceptible to the innate immune response in vitro and behaves as a replicating non-lethal virus in vivo. Remarkably, rNiV lacking W expression results in a delayed and altered disease course with decreased respiratory disease and increased terminal neurological disease associated with altered in vitro inflammatory cytokine production. This study confirms the V protein as the major determinant of pathogenesis, also being the first in vivo study to show that the W protein modulates the inflammatory host immune response in a manner that determines the disease course. PMID:26105519

  12. The search for the ideal influenza vaccine.

    PubMed Central

    Davenport, F. M.

    1979-01-01

    The history of the development of influenza virus vaccine is traced from its origin with experimental studies of influenza virus in ferrets and mice and the first trials in man. Knowledge of the basis of immunity to the viruses in experimental animals and in man has grown steadily over the years and has been essential to successful immunization. Virus variation affecting the surface antigens of the virus is seen as the principal obstacle to the application of vaccines in man. So significant are the changes occurring during antigenic drift that former concepts of a polyvalent vaccine cannot provide a solution of the problem of the composition of vaccines. Disrupted virus vaccines appear to provide the answer to the prevention of vaccine reactions. PMID:461277

  13. Changes to the dynamic nature of hemagglutinin and the emergence of the 2009 pandemic H1N1 influenza virus.

    PubMed

    Yoon, Sun-Woo; Chen, Noam; Ducatez, Mariette F; McBride, Ryan; Barman, Subrata; Fabrizio, Thomas P; Webster, Robert G; Haliloglu, Turkan; Paulson, James C; Russell, Charles J; Hertz, Tomer; Ben-Tal, Nir; Webby, Richard J

    2015-01-01

    The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. While it has been shown that acquisition of the neuraminidase (NA) and matrix (M) gene segments from a Eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09), we show here that an arginine to lysine change in the hemagglutinin (HA) was also necessary. This change at position 149 was distal to the receptor binding site but affected virus-receptor affinity and HA dynamics, allowing the virus to replicate more efficiently in nasal turbinate epithelium and subsequently transmit between ferrets. Receptor affinity should be considered as a factor limiting swine virus spread in humans. PMID:26269288

  14. The cult of personality testing: why assessments are essential for employee selection.

    PubMed

    Bouton, Michael; Moore, Margaret

    2011-01-01

    In today's complex business environment, it is more essential than ever to recognize that talent selection is critical and therefore must be at the top of a manager's list of priorities. It is very difficult to ferret out the important behavioral, motivational, and judgment traits that distinguish an inferior choice from a superior performer. Adding people with high performance capability and low turnover potential adds tremendously to the bottom line. Employing modern psychometric tools that accurately measure total human potential have been categorically proven to: (1) enhance overall productivity; (2) reduce employee attrition; and (3) reduce overall hiring costs significantly. Hiring right every time also mitigates potential damage done to the business both short- and long term from a very bad hire.

  15. Clinical trials with canine distemper vaccines in exotic carnivores.

    PubMed

    Montali, R J; Bartz, C R; Teare, J A; Allen, J T; Appel, M J; Bush, M

    1983-12-01

    Two types of killed canine distemper virus (CDV) vaccine and a modified-live CDV vaccine were clinically evaluated in four species of exotic carnivores. In 16 trials in which 13 red pandas (Ailurus fulgens) were given the killed vaccine, only 1 animal had a virus-neutralization titer that exceeded 1:100. A red panda given modified-live CDV vaccine deemed safe for gray foxes and ferrets died of bacterial pneumonia 16 days later. There was no pathologic evidence of canine distemper in that panda. The same modified-live vaccine proved to be immunogenic and safe in 12 bush dogs (Speothos venaticus), 5 maned wolves (Chrysocyon brachyurus), and 3 fennec foxes (Fennecus zerda) in which virus-neutralization titers often exceeded 1:512 and persisted for several months after vaccination.

  16. Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism.

    PubMed

    Tisoncik-Go, Jennifer; Gasper, David J; Kyle, Jennifer E; Eisfeld, Amie J; Selinger, Christian; Hatta, Masato; Morrison, Juliet; Korth, Marcus J; Zink, Erika M; Kim, Young-Mo; Schepmoes, Athena A; Nicora, Carrie D; Purvine, Samuel O; Weitz, Karl K; Peng, Xinxia; Green, Richard R; Tilton, Susan C; Webb-Robertson, Bobbie-Jo; Waters, Katrina M; Metz, Thomas O; Smith, Richard D; Kawaoka, Yoshihiro; Suresh, M; Josset, Laurence; Katze, Michael G

    2016-02-10

    Pandemic influenza viruses modulate proinflammatory responses that can lead to immunopathogenesis. We present an extensive and systematic profiling of lipids, metabolites, and proteins in respiratory compartments of ferrets infected with either 1918 or 2009 human pandemic H1N1 influenza viruses. Integrative analysis of high-throughput omics data with virologic and histopathologic data uncovered relationships between host responses and phenotypic outcomes of viral infection. Proinflammatory lipid precursors in the trachea following 1918 infection correlated with severe tracheal lesions. Using an algorithm to infer cell quantity changes from gene expression data, we found enrichment of distinct T cell subpopulations in the trachea. There was also a predicted increase in inflammatory monocytes in the lung of 1918 virus-infected animals that was sustained throughout infection. This study presents a unique resource to the influenza research community and demonstrates the utility of an integrative systems approach for characterization of lipid metabolism alterations underlying respiratory responses to viruses.

  17. Tachykinin receptors mediating airway marcomolecular secretion

    SciTech Connect

    Gentry, S.E. )

    1991-01-01

    Three tachykinin receptor types, termed NK1, NK2, and NK3, can be distinguished by the relative potency of various peptides in eliciting tissue responses. Airway macromolecular secretion is stimulated by the tachykinin substance P (SP). The purposes of this study were to determine the tachykinin receptor subtype responsible for this stimulation, and to examine the possible involvement of other neurotransmitters in mediating this effect. Ferret tracheal explants maintained in organ culture were labeled with {sup 3}H-glucosamine, a precursor of high molecular weight glycoconjugates (HMWG) which are released by airway secretory cells. Secretion of labeled HMWG then was determined in the absence and presence of the tachykinins SP, neurokinin A (NKA), neurokinin B (NKB), physalaemin (PHY), and eledoisin (ELE). To evaluate the possible contribution of other mediators, tachykinin stimulation was examined in the presence of several receptor blockers.

  18. Behavioral endpoints for radiation injury

    NASA Astrophysics Data System (ADS)

    Rabin, B. M.; Joseph, J. A.; Hunt, W. A.; Dalton, T. B.; Kandasamy, S. B.; Harris, A. H.; Ludewig, B.

    1994-10-01

    The relative behavioral effectiveness of heavy particles was evaluated. Using the taste aversion paradigm in rats, the behavioral toxicity of most types of radiation (including 20Ne and 40Ar) was similar to that of 60Co photons. Only 56Fe and 93Nb particles and fission neutrons were significantly more effective. Using emesis in ferrets as the behavioral endpoint, 56Fe particles and neutrons were again the most effective; however, 60Co photons were significantly more effective than 18 MeV electrons. These results suggest that LET does not completely predict behavioral effectiveness. Additionally, exposing rats to 10 cGy of 56Fe particles attenuated amphetamine-induced taste aversion learning. This behavior is one of a broad class of behaviors which depends on the integrity of the dopaminergic system and suggests the possibility of alterations in these behaviors following exposure to heavy particles in a space radiation environment.

  19. The descending corticocollicular pathway mediates learning-induced auditory plasticity

    PubMed Central

    Bajo, Victoria M; Nodal, Fernando R; Moore, David R; King, Andrew J

    2013-01-01

    Descending projections from sensory areas of the cerebral cortex are among the largest pathways in the brain, suggesting that they are important for subcortical processing. Although corticofugal inputs have been shown to modulate neuronal responses in the thalamus and midbrain, the behavioral importance of these changes remains unknown. In the auditory system, one of the major descending pathways is from cortical layer V pyramidal cells to the infer