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pathogenicity and transmissibility of reassortant h9 influenza viruses with genes from pandemic h1n1 virus.both h9n2 avian influenza and 2009 pandemic h1n1 viruses (ph1n1) are able to infect humans and swine, which has raised concerns that novel reassortant h9 viruses with ph1n1 genes might be generated in these hosts by reassortment. although previous studies have demonstrated that reassortant h9 viruses with ph1n1 genes show increased virulence in mice and transmissibility in ferrets, the virulence and transmissibility of reassortant h9 viruses in natural hosts such as chickens and swine remain unk ...201222875253
modification and testing of a pneumatic dispensing device for controlled delivery of injectable materials.vocal fold (vf) injections of viscous materials are typically performed using hand-operated syringes or injection guns; however, these methods can be imprecise due to accumulation of pressure, effort-related tremor, and poor feedback regarding injection volume and rate.201222865123
neuroglobin of seals and whales: evidence for a divergent role in the diving brain.although many physiological adaptations of diving mammals have been reported, little is known about how their brains sustain the high demands for metabolic energy and thus o(2) when submerged. a recent study revealed in the deep-diving hooded seal (cystophora cristata) a unique shift of the oxidative energy metabolism and neuroglobin, a respiratory protein that is involved in neuronal hypoxia tolerance, from neurons to astrocytes. here we have investigated neuroglobin in another pinniped species ...201222864183
ventricular septal defect in a ferret (mustela putorius furo).a four-year-old, castrated male ferret (mustela putorius furo) was evaluated because of a one-year history of sporadic cough. on physical examination a grade 5 of 6 holosystolic murmur was audible over the right apex of the heart. radiographic findings included the presence of air bronchograms in apical lobes accompanied by pulmonary venous congestion. colour doppler echocardiography revealed a left-to-right shunting compatible with a ventricular septal defect. medical therapy was initiated at t ...201222861049
reference ranges for laboratory parameters in ferrets.the purpose of this study was to establish reference ranges (robust methods) for 51 laboratory parameters in ferrets for use in private practice. current literature concerning reference values in ferrets is often based on small patient numbers, methods of blood sampling not suitable for practice, and outdated laboratory methods. blood was collected from the v saphena lateralis of 111 clinically healthy ferrets (age 11 weeks to 9 years; 61 male, 50 female). age, sex (male or female) and fasting s ...201222859408
the potential of avian h1n1 influenza a viruses to replicate and cause disease in mammalian models.h1n1 viruses in which all gene segments are of avian origin are the most frequent cause of influenza pandemics in humans; therefore, we examined the disease-causing potential of 31 avian h1n1 isolates of american lineage in dba/2j mice. thirty of 31 isolates were very virulent, causing respiratory tract infection; 22 of 31 resulted in fecal shedding; and 10 of 31 were as pathogenic as the pandemic 2009 h1n1 viruses. preliminary studies in balb/cj mice and ferrets showed that 1 of 4 isolates test ...201222848544
sylvatic plague vaccine: a new tool for conservation of threatened and endangered species?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 manag ...201222846964
novel hepatitis e virus in ferrets, the netherlands. 201222840220
the h275y neuraminidase mutation of the pandemic a/h1n1 influenza virus lengthens the eclipse phase and reduces viral output of infected cells, potentially compromising fitness in ferrets.the h275y amino acid substitution of the neuraminidase gene is the most common mutation conferring oseltamivir resistance in the n1 subtype of the influenza virus. using a mathematical model to analyze a set of in vitro experiments that allow for the full characterization of the viral replication cycle, we show that the primary effects of the h275y substitution on the pandemic h1n1 (h1n1pdm09) strain are to lengthen the mean eclipse phase of infected cells (from 6.6 to 9.1 h) and decrease (by 7- ...201222837199
compromise of auditory cortical tuning and topography after cross-modal invasion by visual inputs.brain damage resulting in loss of sensory stimulation can induce reorganization of sensory maps in cerebral cortex. previous research on recovery from brain damage has focused primarily on adaptive plasticity within the affected modality. less attention has been paid to maladaptive plasticity that may arise as a result of ectopic innervation from other modalities. using ferrets in which neonatal midbrain damage results in diversion of retinal projections to the auditory thalamus, we investigated ...201222836267
brain injury risk from primary blast.military service members are often exposed to at least one explosive event, and many blast-exposed veterans present with symptoms of traumatic brain injury. however, there is little information on the intensity and duration of blast necessary to cause brain injury.201222836001
pathogenicity and transmissibility of north american triple reassortant swine influenza a viruses in ferrets.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 ...201222829764
ferrets further disease research. 201222821038
comparable fitness and transmissibility between oseltamivir-resistant pandemic 2009 and seasonal h1n1 influenza viruses with the h275y neuraminidase mutation.limited antiviral compounds are available for the control of influenza, and the emergence of resistant variants would further narrow the options for defense. the h275y neuraminidase (na) mutation, which confers resistance to oseltamivir carboxylate, has been identified among the seasonal h1n1 and 2009 pandemic influenza viruses; however, those h275y resistant variants demonstrated distinct epidemiological outcomes in humans. specifically, dominance of the h275y variant over the oseltamivir-sensi ...201222811535
both influenza hemagglutinin and polymerase acidic genes are important for delayed pandemic 2009 h1n1 virus clearance in the ferret model.we previously showed that a pandemic virus, a/tennessee/560/09(h1n1), had the potential to adapt to human bronchial epithelial cells by the acquisition of hemagglutinin (ha) k154q and polymerase acidic (pa) protein l295p mutations that conferred a more virulent phenotype. to better elucidate the role of each mutations, we generated recombinant viruses carrying single mutations or both mutations concurrently. the replication of all mutant viruses was significantly higher than that of the wild-typ ...201222809692
ear mite infestation in four imported dogs from thailand; a case report.otodectes cynotis, ear mite or ear canker mite, is the most common cause of otitis external in cats (approximately 50%) and to a lesser extent in dogs, foxes and ferrets. the mite is living on the epidermal surface of auditory canal without burrowing into the tissue and feeding on tissue fluids and debris. in most of the cases they induce hypersensitivity reactions in the host. four puppies; siberian husky, cocker spaniel, terrier and mixed pekignese with different genders and ages were referred ...201022808403
host gene expression signatures discriminate between ferrets infected with genetically similar h1n1 strains.different respiratory viruses induce virus-specific gene expression in the host. recent evidence, including those presented here, suggests that genetically related isolates of influenza virus induce strain-specific host gene regulation in several animal models. here, we identified systemic strain-specific gene expression signatures in ferrets infected with pandemic influenza a/california/07/2009, a/mexico/4482/2009 or seasonal influenza a/brisbane/59/2007. using uncorrelated shrunken centroid cl ...201222808249
recently emerged swine influenza a virus (h2n3) causes severe pneumonia in cynomolgus macaques.the triple reassortant h2n3 virus isolated from diseased pigs in the united states in 2006 is pathogenic for certain mammals without prior adaptation and transmits among swine and ferrets. adaptation, in the h2 hemagglutinin derived from an avian virus, includes the ability to bind to the mammalian receptor, a significant prerequisite for infection of mammals, in particular humans, which poses a big concern for public health. here we investigated the pathogenic potential of swine h2n3 in cynomol ...201222808082
effects of dronabinol on morphine-induced dopamine-related behavioral effects in animals.the present study examined the effects of dronabinol, a united states fda-approved synthetic cannabinoid receptor agonist, on morphine (a prototypic μ-opioid receptor agonist)-induced dopamine-related behaviors in animals. dronabinol suppressed the rewarding effects of morphine in rats and its emetic effects in ferrets. furthermore, the morphine-induced increase in dopamine release from the nucleus accumbens was significantly attenuated by dronabinol, which indicated that the suppressive effects ...201222807156
foxp2 is a parvocellular-specific transcription factor in the visual thalamus of monkeys and ferrets.although the parallel visual pathways are a fundamental basis of visual processing, our knowledge of their molecular properties is still limited. here, we uncovered a parvocellular-specific molecule in the dorsal lateral geniculate nucleus (dlgn) of higher mammals. we found that foxp2 transcription factor was specifically expressed in x cells of the adult ferret dlgn. interestingly, foxp2 was also specifically expressed in parvocellular layers 3-6 of the dlgn of adult old world monkeys, providin ...201322791804
multiple routes of invasion of wild-type clade 1 highly pathogenic avian influenza h5n1 virus into the central nervous system (cns) after intranasal exposure in ferrets.human infections with highly pathogenic avian influenza (hpai) h5n1 have been associated with central nervous system involvement. the purpose of this study was to examine the route of invasion of wild-type hpai h5n1 virus into the central nervous system (cns) using a ferret model of infection. sixteen ferrets were exposed by the intranasal route to 10(6) tcid(50) of a/vietnam/1203/04, a clade 1 strain originally isolated from a fatal human case. the ferrets were euthanased for histological and v ...201222763823
[the role of the auditory cortex in the spatial information processing].sound localization is a computational process accomplished along the auditory pathway. once the acoustic information received at each ear is analyzed independently (monaural cues) and comparatively (binaural cues), those cues are integrated to generate a coherent spatial percept. using adult ferrets trained by positive conditioning in a spatial task, we aimed to study the role of the auditory cortex in the ability to localize sounds under both normal hearing and monaurally occluded conditions, t ...201222760769
evaluation of the efficacy of a pre-pandemic h5n1 vaccine (mg1109) in mouse and ferret models.the threat of a highly pathogenic avian influenza (hpai) h5n1 virus causing the next pandemic remains a major concern. in this study, we evaluated the immunogenicity and efficacy of an inactivated whole-virus h5n1 pre-pandemic vaccine (mg1109) formulated by green cross co., ltd containing the hemagglutinin (ha) and neuraminidase (na) genes of the clade 1 a/vietnam/1194/04 virus in the backbone of a/puerto rico/8/34 (rgvietnam/04xpr8/34). administration of the mg1109 vaccine (2-doses) in mice and ...201222752912
surface glycoproteins of influenza a h3n2 virus modulate virus replication in the respiratory tract of ferrets.the hemagglutinin (ha) genes of the influenza a h3n2 subtype viruses isolated from 1968 to 2010 have evolved substantially but their neuraminidase (na) genes have been relatively less divergent. the h3n2 viruses isolated since 1995 were found to replicate in the lower respiratory tract of ferrets less efficiently than the earlier isolates. to evaluate whether the ha or/and na or the internal protein gene segments of the h3n2 virus affected viral replication in the respiratory tract of ferrets, r ...201222743127
overexpression of serum response factor in astrocytes improves neuronal plasticity in a model of early alcohol exposure.neuronal plasticity deficits underlie many of the cognitive problems seen in fetal alcohol spectrum disorders (fasd). we have developed a ferret model showing that early alcohol exposure leads to a persistent disruption in ocular dominance (od) plasticity. recently, we showed that this deficit could be reversed by overexpression of serum response factor (srf) in the primary visual cortex during the period of monocular deprivation (md). surprisingly, this restoration was observed throughout the e ...201222742904
key molecular factors in hemagglutinin and pb2 contribute to efficient transmission of the 2009 h1n1 pandemic influenza virus.animal influenza viruses pose a clear threat to public health. transmissibility among humans is a prerequisite for a novel influenza virus to cause a human pandemic. a novel reassortant swine influenza virus acquired sustained human-to-human transmissibility and caused the 2009 influenza pandemic. however, the molecular aspects of influenza virus transmission remain poorly understood. here, we show that an amino acid in hemagglutinin (ha) is important for the 2009 h1n1 influenza pandemic virus ( ...201222740390
sparse coding on the spot: spontaneous retinal waves suffice for orientation selectivity.ohshiro, hussain, and weliky (2011) recently showed that ferrets reared with exposure to flickering spot stimuli, in the absence of oriented visual experience, develop oriented receptive fields. they interpreted this as refutation of efficient coding models, which require oriented input in order to develop oriented receptive fields. here we show that these data are compatible with the efficient coding hypothesis if the influence of spontaneous retinal waves is considered. we demonstrate that ind ...201222734490
airborne transmission of influenza a/h5n1 virus between ferrets.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 ...201222723413
experimental adaptation of an influenza h5 ha confers respiratory droplet transmission to a reassortant h5 ha/h1n1 virus in ferrets.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 as it mediates virus binding to host-specific cellular receptors. here we assess the molecular changes in ha that would allow a virus possessing subtype h5 ha to be transmissible among mammals. we identified a reassortant h5 ha/h1n1 virus-comprising h5 ha (from an h5n1 virus) with four mutation ...201222722205
engineering h5n1 avian influenza viruses to study human adaptation.two studies of h5n1 avian influenza viruses that had been genetically engineered to render them transmissible between ferrets have proved highly controversial. divergent opinions exist about the importance of these studies of influenza transmission and about potential 'dual use' research implications. no consensus has developed yet about how to balance these concerns. after not recommending immediate full publication of earlier, less complete versions of the studies, the united states national s ...201222722191
characterization in vitro and in vivo of pandemic (h1n1) 2009 influenza viruses isolated from patients.the first influenza pandemic of the 21st century was caused by novel h1n1 viruses that emerged in early 2009. molecular evolutionary analyses of the 2009 pandemic influenza a h1n1 [a(h1n1)pdm09] virus revealed two major clusters, cluster i and cluster ii. although the pathogenicity of viruses belonging to cluster i, which became extinct by the end of 2009, has been examined in a nonhuman primate model, the pathogenic potential of viruses belonging to cluster ii, which has spread more widely in t ...201222718834
rapid and efficient genetic manipulation of gyrencephalic carnivores using in utero electroporation.higher mammals such as primates and carnivores have highly developed unique brain structures such as the ocular dominance columns in the visual cortex, and the gyrus and outer subventricular zone of the cerebral cortex. however, our molecular understanding of the formation, function and diseases of these structures is still limited, mainly because genetic manipulations that can be applied to higher mammals are still poorly available.201222716093
the current state of h5n1 vaccines and the use of the ferret model for influenza therapeutic and prophylactic development.highly pathogenic avian influenza h5n1 is a threat to global public health as a natural pandemic causing agent but has recently been considered a bioterrorism concern.  the evolving view of the h5n1 virus necessitates the re-evaluation of the current status of h5n1 therapeutics and prophylactics, in particular the preparation of viable h5n1 vaccination strategies as well as the use of ferrets in influenza research.  here the highly pathogenic h5n1 virus dilemma is discussed in context with the c ...201222706187
evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. for measles and canine distemper virus (cdv) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. we recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvan ...201222705079
signal detection in animal psychoacoustics: analysis and simulation of sensory and decision-related influences.signal detection theory (sdt) provides a framework for interpreting psychophysical experiments, separating the putative internal sensory representation and the decision process. sdt was used to analyse ferret behavioural responses in a (yes-no) tone-in-noise detection task. instead of measuring the receiver-operating characteristic (roc), we tested sdt by comparing responses collected using two common psychophysical data collection methods. these (constant stimuli, limits) differ in the set of s ...201222698686
concurrent 2009 pandemic influenza a (h1n1) virus infection in ferrets and in a community in pennsylvania.we report a fall 2010 cluster of pandemic influenza a/h1n1 (ph1n1) infections in pet ferrets in lehigh valley region of pennsylvania. the ferrets were associated with one pet shop. the influenza cluster occurred during a period when the existing human surveillance systems had identified little to no ph1n1 in humans in the lehigh valley, and there were no routine influenza surveillance systems for exotic pets. the index case was a 2.5-month-old neutered male ferret that was presented to a veterin ...201322697485
a quantitative analysis of information about past and present stimuli encoded by spikes of a1 neurons.to process the rich temporal structure of their acoustic environment, organisms have to integrate information over time into an appropriate neural response. previous studies have addressed the modulation of responses of auditory neurons to a current sound in dependence of the immediate stimulation history, but a quantitative analysis of this important computational process has been missing. in this study, we analyzed temporal integration of information in the spike output of 122 single neurons i ...201222696538
auditory nerve fibre responses in the ferret.the ferret (mustela putorius) is a medium-sized, carnivorous mammal with good low-frequency hearing; it is relatively easy to train, and there is therefore a good body of behavioural data detailing its detection thresholds and localization abilities. however, despite extensive studies of the physiology of the central nervous system of the ferret, even extending to the prefrontal cortex, little is known of the functioning of the auditory periphery. here, we provide an insight into this peripheral ...201222694786
contribution of pheromones processed by the main olfactory system to mate recognition in female mammals.until recently it was widely believed that the ability of female mammals (with the likely exception of women) to identify and seek out a male breeding partner relied on the detection of non-volatile male pheromones by the female's vomeronasal organ (vno) and their subsequent processing by a neural circuit that includes the accessory olfactory bulb (aob), vomeronasal amygdala, and hypothalamus. emperical data are reviewed in this paper that demonstrate the detection of volatile pheromones by the ...201222679420
five cases of contact dermatitis to a trendy pet.skin contact with animal hair may induce contact urticaria (syndrome) or protein contact dermatitis. we report here 5 cases of dermatitis due to contact with ferrets kept as pets. the nature of the skin lesions, i.e. eczematous dermatitis, as well as the history of our 5 cases point to protein contact dermatitis. further studies are requested to confirm this hypothesis and to identify the mechanisms and allergens. physicians must be aware of the possibility of contact dermatitis with ferrets, es ...201222677934
low pathogenic avian influenza isolates from wild birds replicate and transmit via contact in ferrets without prior adaptation.direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. we have previously demonstrated the capacity of numerous north american avian influenza viruses isolated from wild b ...201222675507
effect of priming with h1n1 influenza viruses of variable antigenic distances on challenge with 2009 pandemic h1n1 virus.compared to seasonal influenza viruses, the 2009 pandemic h1n1 (ph1n1) virus caused greater morbidity and mortality in children and young adults. people over 60 years of age showed a higher prevalence of cross-reactive ph1n1 antibodies, suggesting that they were previously exposed to an influenza virus or vaccine that was antigenically related to the ph1n1 virus. to define the basis for this cross-reactivity, ferrets were infected with h1n1 viruses of variable antigenic distance that circulated ...201222674976
[heart abnormalities in the cat, dog and ferret]. 201222667184
wired on steroids: sexual differentiation of the brain and its role in the expression of sexual partner preferences.the preference to seek out a sexual partner of the opposite sex is robust and ensures reproduction and survival of the species. development of female-directed partner preference in the male is dependent on exposure of the developing brain to gonadal steroids synthesized during critical periods of sexual differentiation of the central nervous system. in the absence of androgen exposure, a male-directed partner preference develops. the development and expression of sexual partner preference has be ...201122654808
an optimized real-time pcr to avoid species-/tissue-associated inhibition for h5n1 detection in ferret and monkey tissues.the real-time pcr diagnostics for avian influenza virus h5n1 in tissue specimens are often suboptimal, since naturally occurring pcr inhibitors present in samples, or unanticipated match of primer to unsequenced species' genome. with the principal aim of optimizing the sybr green real-time pcr method for detecting h5n1 in ferret and monkey (chinese rhesus macaque) tissue specimens, we screened various h5n1 gene-specific primer pairs and tested their ability to sensitively and specifically detect ...201222645461
mechanisms underlying azimuth selectivity in the auditory cortex of the pallid bat.this study focused on mechanisms underlying azimuth selectivity in the primary auditory cortex (a1) of pallid bats. the pallid bat listens to prey-generated noise (5-35 khz) to localize and hunt terrestrial prey. the region of a1 tuned between 5 and 35 khz consists of two clusters of neurons distinguished by interaural intensity difference (iid) selectivity: binaurally inhibited (ei) and peaked. the first aim of this study was to use sequential dichotic/free-field stimulation to test the hypothe ...201222641192
the 2009 pandemic influenza virus: where did it come from, where is it now, and where is it going?around 2008 or 2009, an influenza a virus that had been circulating undetected in swine entered human population. unlike most swine influenza infections of humans, this virus established sustained human-to-human transmission, leading to a global pandemic. the virus responsible, 2009 pandemic h1n1 (h1n1pdm), is the result of multiple reassortment events that brought together genomic segments from classical h1n1 swine influenza virus, human seasonal h3n2 influenza virus, north american avian influ ...201322638836
initial neighborhood biases and the quality of motion stimulation jointly influence the rapid emergence of direction preference in visual cortex.visual experience plays a critical role in the development of direction-selective responses in ferret visual cortex. in visually naive animals, presentation of a bidirectional "training" stimulus induces rapid increases in the direction-selective responses of single neurons that can be predicted by small but significant direction biases that are present in neighboring neurons at the onset of stimulation. in this study we used in vivo two-photon imaging of calcium signals to further explore the c ...201222623671
inter- and intraspecies transmission of canine influenza virus (h3n2) in dogs, cats, and ferrets.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.201322616918
de-novo transcriptome sequencing of a normalized cdna pool from influenza infected ferrets.the ferret is commonly used as a model for studies of infectious diseases. the genomic sequence of this animal model is not yet characterized, and only a limited number of fully annotated cdnas are currently available in genbank. the majority of genes involved in innate or adaptive immune response are still lacking, restricting molecular genetic analysis of host response in the ferret model. to enable de novo identification of transcriptionally active ferret genes in response to infection, we pe ...201222606336
porcine head response to blast.recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. however, the mechanisms that cause blast neurotrauma are unknown. blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. however, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical res ...201222586417
in vivo evaluation of pathogenicity and transmissibility of influenza a(h1n1)pdm09 hemagglutinin receptor binding domain 222 intrahost variants isolated from a single immunocompromised patient.the influenza a(h1n1)pdm09 virus has circulated worldwide and continued to cause complicated infections and deaths. reports have identified an increased prevalence of the hemagglutinin receptor binding domain d222g mutation in viruses isolated from individuals who have suffered such severe infections, but this association is still unclear. virus isolated from a nasopharyngeal wash of a severely ill immunocompromised patient at the time of diagnosis contained the d222, but isolates collected late ...201222575875
comparative processing and function of human and ferret cystic fibrosis transmembrane conductance regulator.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. t ...201222570484
discovery of a novel orally active pde-4 inhibitor effective in an ovalbumin-induced asthma murine model.phosphodiesterase-4 (pde-4) is responsible for metabolizing adenosine 3',5'-cyclic monophosphate that reduces the activation of a wide range of inflammatory cells including eosinophils. pde-4 inhibitors are under development for the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease. herein, we report a novel pde-4 inhibitor, pde-423 (3-[1-(3-cyclopropylmethoxy-4-difluoromethoxybenzyl)-1h-pyrazol-3-yl]-benzoic acid), which shows good in vitro and in vivo o ...201222554769
recombinant canine distemper virus strain snyder hill expressing green or red fluorescent proteins causes meningoencephalitis in the ferret.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 (cdv(sh)) 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 cdv(sh) (rcdv(sh)) expressing enhance ...201222553334
seasonal trivalent inactivated influenza vaccine protects against 1918 spanish influenza virus infection in ferrets.the influenza virus h1n1 pandemic of 1918 was one of the worst medical catastrophes in human history. recent studies have demonstrated that the hemagglutinin (ha) protein of the 1918 virus and 2009 h1n1 pandemic virus [a(h1n1)pdm09], the latter now a component of the seasonal trivalent inactivated influenza vaccine (tiv), share cross-reactive antigenic determinants. in this study, we demonstrate that immunization with the 2010-2011 seasonal tiv induces neutralizing antibodies that cross-react wi ...201222553323
plasticity of spatial hearing: behavioural effects of cortical inactivation.the cerebral cortex plays a critical role in perception and in learning-induced plasticity. we show that reversibly silencing any of the main regions of auditory cortex impairs the ability of adult ferrets to localize sound, with the largest deficit seen after deactivating the primary fields. although these animals had no trouble localizing longer sound bursts, their performance dropped considerably when auditory spatial cues were altered by occluding one ear with an earplug. in contrast to cont ...201222547635
mustelidae are natural hosts of staphylococcus delphini group a.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 ...201222542523
immunization with sars coronavirus vaccines leads to pulmonary immunopathology on challenge with the sars virus.severe acute respiratory syndrome (sars) emerged in china in 2002 and spread to other countries before brought under control. because of a concern for reemergence or a deliberate release of the sars coronavirus, vaccine development was initiated. evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease.201222536382
dynamics of phase-independent spectro-temporal tuning in primary auditory cortex of the awake ferret.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 measured 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-independent tuning during feature transients. based on previous results, ...201222531376
intramedullary lumbosacral teratoma in a domestic ferret (mustela putorius furo).an 18-month-old, female, spayed domestic ferret (mustela putorius furo) was presented for progressive hind limb paresis of 1 week duration. the ferret was mentally appropriate but cachexic and ataxic with neurological deficits, which localized the lesion to the lumbosacral region. a depression in the lumbosacral spine was associated with discomfort on palpation. results of whole body radiographs were consistent with an abnormal angle between vertebrae l6 and s1, which resulted in hyperflexion of ...201222529139
endogenous lentiviral elements in the weasel family (mustelidae).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 ...201222522310
multisensory dysfunction accompanies crossmodal plasticity following adult hearing impairment.until now, cortical crossmodal plasticity has largely been regarded as the effect of early and complete sensory loss. recently, massive crossmodal cortical reorganization was demonstrated to result from profound hearing loss in adult ferrets (allman et al., 2009a). moderate adult hearing loss, on the other hand, induced not just crossmodal reorganization, but also merged new crossmodal inputs with residual auditory function to generate multisensory neurons. because multisensory convergence can l ...201222516008
exhaled aerosol transmission of pandemic and seasonal h1n1 influenza viruses in the ferret.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 an ...201222509254
post-anesthesia vomiting: impact of isoflurane and morphine on ferrets and musk shrews.although partially controlled with antiemetic drugs, postoperative nausea and vomiting (ponv) continues to be a problem for many patients. clinical research suggests that opioid analgesics and volatile anesthetics are the main triggers of ponv. the aim of this study was to develop an animal model for post-anesthesia vomiting for future studies to further determine mechanisms and preclinical drug efficacy. ferrets (n=34) were initially used because they have served as a gold standard for emesis r ...201222504494
a review of pathophysiology and management of fetuses and neonates with meconium ileus for the pediatric surgeon.meconium ileus (mi) is the earliest clinical manifestation of cystic fibrosis (cf), occurring in up to 20% of patients with cf. our aim was to review and integrate current knowledge about the diagnosis and management of fetuses and neonates with mi that may aid the pediatric surgeon in caring for these patients.201222498395
rolapitant (sch 619734): a potent, selective and orally active neurokinin nk1 receptor antagonist with centrally-mediated antiemetic effects in ferrets.nk1 receptor antagonists have been shown to have a variety of physiological and potential therapeutic effects in animal models and in humans. the present studies demonstrate that rolapitant (sch 619734, (5s)-8(s)-[[1(r)-[3,5 bis(trifluoromethyl)phenyl]ethoxy]methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one) is a selective, bioavailable, cns penetrant neurokinin nk1 receptor antagonist that shows behavioral effects in animals models of emesis. in vitro studies indicate that rolapitant has a high a ...201222497992
a triclade dna vaccine designed on the basis of a comprehensive serologic study elicits neutralizing antibody responses against all clades and subclades of highly pathogenic avian influenza h5n1 viruses.because of their rapid evolution, genetic diversity, broad host range, ongoing circulation in birds, and potential human-to-human transmission, h5n1 influenza viruses remain a major global health concern. their high degree of genetic diversity also poses enormous burdens and uncertainties in developing effective vaccines. to overcome this, we took a new approach, i.e., the development of immunogens based on a comprehensive serologic study. we constructed dna plasmids encoding codon-optimized hem ...201222496212
evaluation of influenza virus a/h3n2 and b vaccines on the basis of cross-reactivity of postvaccination human serum antibodies against influenza viruses a/h3n2 and b isolated in mdck cells and embryonated hen eggs.the vaccine strains against influenza virus a/h3n2 for the 2010-2011 season and influenza virus b for the 2009-2010 and 2010-2011 seasons in japan are a high-growth reassortant a/victoria/210/2009 (x-187) strain and an egg-adapted b/brisbane/60/2008 (victoria lineage) strain, respectively. hemagglutination inhibition (hi) tests with postinfection ferret antisera indicated that the antisera raised against the x-187 and egg-adapted b/brisbane/60/2008 vaccine production strains poorly inhibited rec ...201222492743
dendritic spine density in multisensory versus primary sensory cortex.in sensory areas, neuronal dendritic spines receive sensory-specific inputs whose net activity drives neuronal spiking responses to effective external stimuli. previous studies indicate that neurons in primary sensory cortical areas, which largely receive inputs from a single sensory modality, exhibit an average of 0.5-1.4 dendritic spines/μm, depending on species. in higher-order, associational cortices, inputs converge from multiple sensory sources onto individual, multisensory neurons. this r ...201222488884
animal challenge models of henipavirus infection and pathogenesis.the henipaviruses, hendra virus (hev), and nipah virus (niv), are enigmatic emerging pathogens that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. amongst people, case fatality rates range between 40 and 75% and there are no vaccines or treatments approved for human use. a number of species of animals including guinea pigs, hamsters, cats, ferrets, pigs, and african green monkeys have been employed as animal models of human henipavirus infection. ...201222476556
control of pandemic (h1n1) 2009 influenza virus infection of ferret lungs by non-adjuvant-containing pandemic and seasonal vaccines.the pandemic h1n1 2009 influenza virus caused relatively mild disease in most infected people but some suffered extensively from primary lung infection, many more than would have occurred with seasonal influenza infection. early commercially available pandemic h1n1 vaccines did not contain adjuvant, as did many of the subsequent vaccines, and could not stop infection with the pandemic virus in vaccinated ferrets. nevertheless, we showed that virus loads in the lungs were greatly diminished in fe ...201222464969
the future of research and publication on altered h5n1 viruses.recently, we and others obtained experimental evidence that highly pathogenic avian influenza virus subtype h5 can acquire the ability to transmit via aerosols between ferrets. upon submission of manuscripts describing the results of these studies, the us national science advisory board for biosecurity was consulted and recommended that the main conclusions of the work be published but without the experimental details and mutation data that would enable replication of the experiments. over the p ...201222454474
wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high'.humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the 'runner's high', which may function to encourage habitual aerobic exercise. endocannabinoids (ecbs) are endogenous neurotransmitters that appear to play a major role in generating these rewards by activating cannabinoid receptors in brain reward regions during and after exercise. other species also regularly engage in endurance exercise (cursorial mammals), and as h ...201222442371
fitness of neuraminidase inhibitor-resistant influenza a viruses.antiviral drugs are important components for the control of influenza. the key question is whether antiviral use or natural virus evolution will lead to the emergence of drug-resistant virus with comparable or superior fitness to drug-susceptible counterpart. currently, neuraminidase (na) inhibitors (nais) are the first choice for influenza prevention and treatment. in this article we will review complex process of the risk assessment for the fitness of nais-resistant seasonal h1n1 and h3n2, pan ...201122440915
role of ca(2+) in the rapid cooling-induced ca(2+) release from sarcoplasmic reticulum in ferret cardiac muscles.rapid lowering of the solution temperature (rapid cooling, rc) from 24 to 3°c within 3 s releases considerable amounts of ca(2+) from the sarcoplasmic reticulum (sr) in mammalian cardiac muscles. in this study, we investigated the intracellular mechanism of rc-induced ca(2+) release, especially the role of ca(2+), in ferret ventricular muscle. saponin-treated skinned trabeculae were placed in a glass capillary, and the amount of ca(2+) released from the sr by rc and caffeine (50 mm) was measured ...201222431072
aleutian disease in the ferret.ferrets inoculated with aleutian disease (ad)-infective material of mink origin harbored the infective agent for at least 136 days after inoculation. in contrast, hamsters given a similar inoculum of infective material no longer harbored the infective agent at 21 days postinoculation. during the infective period, neither ferrets nor hamsters had any detectable illness. however, in certain ferrets, massive periportal lymphocytic infiltrates were observed. a survey of ferrets from different ranche ...196622413203
ferretting out the facts behind the h5n1 controversy.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.201522402712
fabrication of an inexpensive, implantable cooling device for reversible brain deactivation in animals ranging from rodents to primates.we have developed a compact and lightweight microfluidic cooling device to reversibly deactivate one or more areas of the neocortex to examine its functional macrocircuitry as well as behavioral and cortical plasticity. the device, which we term the "cooling chip," consists of thin silicone tubing (through which chilled ethanol is circulated) embedded in mechanically compliant polydimethylsiloxane (pdms). pdms is tailored to compact device dimensions (as small as 21 mm(3)) that precisely accommo ...201222402651
influenza virus respiratory infection and transmission following ocular inoculation in ferrets.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 entry for establishment of a respiratory infection. however, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the p ...201222396651
working safely with h5n1 viruses.research on h5n1 influenza viruses has received much attention recently due to the possible dangers associated with newly developed avian h5n1 viruses that were derived from highly pathogenic avian viruses and are now transmissible among ferrets via respiratory droplets. an appropriate discussion, based on scientific facts about the risks that such viruses pose and on the biocontainment facilities and practices necessary for working safely with these viruses, is needed. selecting the right level ...201222396483
ferret-transmissible influenza a(h5n1) virus: let us err on the side of caution. 201222396481
influenza virus h1n1pdm09 infections in the young and old: evidence of greater antibody diversity and affinity for the hemagglutinin globular head domain (ha1 domain) in the elderly than in young adults and children.the h1n1 2009 influenza virus (h1n1pdm09) pandemic had several unexpected features, including low morbidity and mortality in older populations. we performed in-depth evaluation of antibody responses generated following h1n1pdm09 infection of naïve ferrets and of 130 humans ranging from the very young (0 to 9 years old) to the very old (70 to 89 years old). in addition to hemagglutination inhibition (hi) titers, we used h1n1pdm09 whole-genome-fragment phage display libraries (gfpdl) to evaluate t ...201222379097
spatial and temporal variations of cortical growth during gyrogenesis in the developing ferret brain.spatial and temporal variations in cortical growth were studied in the neonatal ferret to illuminate the mechanisms of folding of the cerebral cortex. cortical surface representations were created from magnetic resonance images acquired between postnatal day 4 and 35. global measures of shape (e.g., surface area, normalized curvature, and sulcal depth) were calculated. in 2 ferrets, relative cortical growth was calculated between surfaces created from in vivo images acquired at p14, p21, and p28 ...201322368085
mammalian-transmissible h5n1 influenza: facts and perspective.two recently submitted (but as yet unpublished) studies describe success in creating mutant isolates of h5n1 influenza a virus that can be transmitted via the respiratory route between ferrets; concern has been raised regarding human-to-human transmissibility of these or similar laboratory-generated influenza viruses. furthermore, the potential release of methods used in these studies has engendered a great deal of controversy around publishing potential dual-use data and also has served as a ca ...201222366820
decoding the distribution of glycan receptors for human-adapted influenza a viruses in ferret respiratory tract.ferrets are widely used as animal models for studying influenza a viral pathogenesis and transmissibility. human-adapted influenza a viruses primarily target the upper respiratory tract in humans (infection of the lower respiratory tract is observed less frequently), while in ferrets, upon intranasal inoculation both upper and lower respiratory tract are targeted. viral tropism is governed by distribution of complex sialylated glycan receptors in various cells/tissues of the host that are specif ...201222359533
pathogenesis and transmission of swine origin a(h3n2)v influenza viruses in ferrets.recent isolation of a novel swine-origin influenza a h3n2 variant virus [a(h3n2)v] from humans in the united states has raised concern over the pandemic potential of these viruses. here, we analyzed the virulence, transmissibility, and receptor-binding preference of four a(h3n2)v influenza viruses isolated from humans in 2009, 2010, and 2011. high titers of infectious virus were detected in nasal turbinates and nasal wash samples of a(h3n2)v-inoculated ferrets. all four a(h3n2)v viruses possesse ...201222355116
dangerous for ferrets: lethal for humans? 201222348706
a new orally active, aminothiol radioprotector-free of nausea and hypotension side effects at its highest radioprotective doses.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).201222330992
the 2009 pandemic h1n1 virus induces anti-neuraminidase (na) antibodies that cross-react with the na of h5n1 viruses in ferrets.a miniaturized neuraminidase inhibition (ni) assay using ha-mismatched h6 reassortant viruses was performed to examine the neuraminidase (na)-specific antibody response in ferrets immunized with live-attenuated influenza vaccine (laiv) strains. the strains tested possessed different nas derived from seasonal h1n1 and h3n2, 2009 pandemic h1n1, and the highly pathogenic influenza h5n1 virus. the anti-na antibodies from the 2009 pandemic strain (a/california/7/2009) immunized ferrets cross-reacted ...201222330124
contrast tuned responses in primary auditory cortex of the awake ferret.auditory neurons are often characterized by their spectro-temporal receptive field (strf), a linear measure that captures overall trends of neural responses to modulations of the spectro-temporal envelopes of sounds. we have previously shown that primary auditory cortex neurons of the awake ferret are better characterized by strfs followed by a non-trivial non-linearity. this non-linearity is a half-wave rectification followed by a squaring function, indicating that cortical neurons probably enc ...201222321018
the first case of feline infectious peritonitis-like pyogranuloma in a ferret infected by coronavirus in japan.a male ferret, which was purchased from abroad at 9 months of age, had shown significant weight loss starting at 13 months of age. the ferret subsequently showed decreasing motor activity and recumbency and was euthanized at 14 months of age. at necropsy, a white, quail egg-sized mass was found in the mesentery. histopathologically, multifocal granulomas consisting of necrotic foci, macrophages, fibroblasts and plentiful fibrous connective tissues were observed in the mesenteric mass. surroundin ...201022319227
pb1-f2 modulates early host responses but does not affect the pathogenesis of h1n1 seasonal influenza virus.in the context of infections with highly pathogenic influenza a viruses, the pb1-f2 protein contributes to virulence and enhances lung inflammation. in contrast, its role in the pathogenesis of seasonal influenza viral strains is less clear, especially in the h1n1 subtype, where strains can have a full-length 87- to 90-amino-acid protein, a truncated 57-amino-acid version, or lack the protein altogether. toward this, we introduced the full-length 1918 pb1-f2, or prevented pb1-f2 expression, in h ...201222318139
h5n1 influenza viruses: facts, not fear.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 ...201222308474
task reward structure shapes rapid receptive field plasticity in auditory cortex.as sensory stimuli and behavioral demands change, the attentive brain quickly identifies task-relevant stimuli and associates them with appropriate motor responses. the effects of attention on sensory processing vary across task paradigms, suggesting that the brain may use multiple strategies and mechanisms to highlight attended stimuli and link them to motor action. to better understand factors that contribute to these variable effects, we studied sensory representations in primary auditory cor ...201222308415
functional biases in visual cortex neurons with identified projections to higher cortical targets.visual perception involves information flow from lower- to higher-order cortical areas, which are known to process different kinds of information. how does this functional specialization arise? as a step toward addressing this question, we combined fluorescent retrograde tracing with in vivo two-photon calcium imaging to simultaneously compare the tuning properties of neighboring neurons in areas 17 and 18 of ferret visual cortex that have different higher cortical projection targets.201222305753
pandemic (h1n1) 2009 in captive cheetah.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.201222305505
avian influenza. the limits of avian flu studies in ferrets. 201222301288
science should be in the public domain.variants of avian influenza h5n1 virus that are transmitted by the airborne route among ferrets have been identified. the national science advisory board for biosecurity has advised against publication of the details of the methods used to obtain these viruses and the amino acid changes that lead to transmission in ferrets. this decision is not based on sound scientific principles and risks setting a precedent that will make it easier to put in place highly restrictive regulations on scientific ...201222294675
urine specific gravity values in clinically healthy young pet ferrets (mustela furo).to determine urine specific gravity values in clinically healthy pet ferrets and explore possible associations with sex, sampling techniques, hydration status and urine analytes.201222283794
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