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animal models of respiratory syncytial virus infection.human respiratory syncytial virus (hrsv) is a major cause of respiratory disease and hospitalisation of infants, worldwide, and is also responsible for significant morbidity in adults and excess deaths in the elderly. there is no licensed hrsv vaccine or effective therapeutic agent. however, there are a growing number of hrsv vaccine candidates that have been developed targeting different populations at risk of hrsv infection. animal models of hrsv play an important role in the preclinical testi ...201727908639
using galleria mellonella as an infection model for campylobacter jejuni pathogenesis.nonmammalian model systems of infection have been employed recently to study bacterial virulence. for instance, galleria mellonella (the greater wax moth) has been shown to be susceptible to infection by many bacterial pathogens including the enteric pathogen campylobacter jejuni. in contrast to the traditional animal models for c. jejuni such as the chick colonization model and ferret diarrheal model, the galleria mellonella infection model has the advantages of lower cost, ease of use and no a ...201727885606
inactivated recombinant rabies viruses displaying canine distemper virus glycoproteins induce protective immunity against both pathogens.the development of multivalent vaccines is an attractive methodology for the simultaneous prevention of several infectious diseases in vulnerable populations. both canine distemper virus (cdv) and rabies virus (rabv) cause lethal disease in wild and domestic carnivores. while rabv vaccines are inactivated, the live-attenuated cdv vaccines retain residual virulence for highly susceptible wildlife species. in this study, we developed recombinant bivalent vaccine candidates based on recombinant vac ...201728148801
development of an anti-ferret cd4 monoclonal antibody for the characterisation of ferret t lymphocytes.the ferret is an established animal model for a number of human respiratory viral infections, such as influenza virus and more recently, ebola virus. however, a paucity of immunological reagents has hampered the study of cellular immune responses. here we describe the development and characterisation of a novel monoclonal antibody (mab) against the ferret cd4 antigen and the characterisation of ferret cd4 t lymphocytes. recombinant production and purification of the ferret cd4 ectodomain soluble ...201728216237
safe recombinant outer membrane vesicles that display m2e elicit heterologous influenza protection.recombinant, escherichia coli-derived outer membrane vesicles (romvs), which display heterologous protein subunits, have potential as a vaccine adjuvant platform. one drawback to romvs is their lipopolysaccharide (lps) content, limiting their translatability to the clinic due to potential adverse effects. here, we explore a unique romv construct with structurally remodeled lipids containing only the lipid iva portion of lps, which does not stimulate human tlr4. the romvs are derived from a genet ...201728215994
molecular epidemiology of influenza a(h1n1)pdm09 hemagglutinin gene circulating in são paulo state , brazil: 2016 anticipated influenza season.compared to previous years, seasonal influenza activity commenced early in são paulo state, brazil, southern hemisphere during the 2016 year. in order to investigate the genetic pattern of influenza a(h1n1)pdm09 in the state of sao paulo a total of 479 respiratory samples, collected in january by sentinel surveillance units, were screened by real-time rt-pcr. a total of 6 influenza viruses a(h1n1)pdm09 presenting ct values ≤ 30 were sequenced following phylogenetic analysis. the present study id ...201728380120
h1n1 influenza viruses varying widely in hemagglutinin stability transmit efficiently from swine to swine and to ferrets.a pandemic-capable influenza virus requires a hemagglutinin (ha) surface glycoprotein that is immunologically unseen by most people and is capable of supporting replication and transmission in humans. ha stabilization has been linked to 2009 ph1n1 pandemic potential in humans and h5n1 airborne transmissibility in the ferret model. swine have served as an intermediate host for zoonotic influenza viruses, yet the evolutionary pressure exerted by this host on ha stability was unknown. for over 70 c ...201728282440
generation of a live attenuated influenza vaccine that elicits broad protection in mice and ferrets.new influenza vaccines that provide effective and broad protection are desperately needed. live attenuated viruses are attractive vaccine candidates because they can elicit both humoral and cellular immune responses. however, recent formulations of live attenuated influenza vaccines (laivs) have not been protective. we combined high-coverage transposon mutagenesis of influenza virus with a rapid high-throughput screening for attenuation to generate w7-791, a live attenuated mutant virus strain. ...201728279345
selection of multi-drug resistant influenza a and b viruses under zanamivir pressure and their replication fitness in ferrets.intravenous zanamivir has been used to treat patients with severe influenza. because the majority of cases (including immunocompromised patients) require the drug for an extended period of treatment, there is a higher risk that the virus will develop resistance. therefore, knowing the possible amino acid substitutions that may arise in recently circulating influenza strains under prolonged zanamivir exposure and their impact on antiviral susceptibility is important.201728195559
defining the antibody cross-reactome directed against the influenza virus surface glycoproteins.infection with influenza virus induces antibodies to the viral surface glycoproteins hemagglutinin and neuraminidase, and these responses can be broadly protective. to assess the breadth and magnitude of antibody responses, we sequentially infected mice, guinea pigs and ferrets with divergent h1n1 or h3n2 subtypes of influenza virus. we measured antibody responses by elisa of an extensive panel of recombinant glycoproteins representing the viral diversity in nature. guinea pigs developed high ti ...201728192418
swine influenza virus (h1n2) characterization and transmission in ferrets, chile.phylogenetic analysis of the influenza hemagglutinin gene (ha) has suggested that commercial pigs in chile harbor unique human seasonal h1-like influenza viruses, but further information, including characterization of these viruses, was unavailable. we isolated influenza virus (h1n2) from a swine in a backyard production farm in central chile and demonstrated that the ha gene was identical to that in a previous report. its ha and neuraminidase genes were most similar to human h1 and n2 viruses f ...201728098524
recent h3n2 viruses have evolved specificity for extended, branched human-type receptors, conferring potential for increased avidity.human and avian influenza viruses recognize different sialic acid-containing receptors, referred to as human-type (neuacα2-6gal) and avian-type (neuacα2-3gal), respectively. this presents a species barrier for aerosol droplet transmission of avian viruses in humans and ferrets. recent reports have suggested that current human h3n2 viruses no longer have strict specificity toward human-type receptors. using an influenza receptor glycan microarray with extended airway glycans, we find that h3n2 vi ...201728017661
occurrence and molecular genotyping of giardia duodenalis and cryptosporidium spp. in wild mesocarnivores in spain.there is a surprisingly scarce amount of epidemiological and molecular data on the prevalence, frequency, and diversity of the intestinal protozoan parasites giardia duodenalis and cryptosporidium spp. in wildlife in general and mesocarnivore species in particular. consequently, the extent of the cyst/oocyst environmental contamination attributable to these wild host species and their potential implications for public veterinary health remain largely unknown. in this molecular epidemiological su ...201728215875
novel highly pathogenic avian a(h5n2) and a(h5n8) influenza viruses of clade 2.3.4.4 from north america have limited capacity for replication and transmission in mammals.highly pathogenic influenza a(h5n8) viruses from clade 2.3.4.4 were introduced to north america by migratory birds in the fall of 2014. reassortment of a(h5n8) viruses with avian viruses of north american lineage resulted in the generation of novel a(h5n2) viruses with novel genotypes. through sequencing of recent avian influenza viruses, we identified pb1 and np gene segments very similar to those in the viruses isolated from north american waterfowl prior to the introduction of a(h5n8) to nort ...201727303732
amino acids in hemagglutinin antigenic site b determine antigenic and receptor binding differences between a(h3n2)v and ancestral seasonal h3n2 influenza viruses.influenza a h3n2 variant [a(h3n2)v] viruses, which have caused human infections in the united states in recent years, originated from human seasonal h3n2 viruses that were introduced into north american swine in the mid-1990s, but they are antigenically distinct from both the ancestral and current circulating h3n2 strains. a reference a(h3n2)v virus, a/minnesota/11/2010 (mn/10), and a seasonal h3n2 strain, a/beijing/32/1992 (bj/92), were chosen to determine the molecular basis for the antigenic ...201727807224
evolution and divergence of h3n8 equine influenza viruses circulating in the united kingdom from 2013 to 2015.equine influenza viruses (eiv) are a major cause of acute respiratory disease in horses worldwide and occasionally also affect vaccinated animals. like other influenza a viruses, they undergo antigenic drift, highlighting the importance of both surveillance and virus characterisation in order for vaccine strains to be kept up to date. the aim of the work reported here was to monitor the genetic and antigenic changes occurring in eiv circulating in the uk from 2013 to 2015 and to identify any evi ...201728208721
the immune correlates of protection for an avian influenza h5n1 vaccine in the ferret model using oil-in-water adjuvants.because of the pathogenicity and low incidence of avian influenza virus infections in humans, the immune correlates of protection for avian influenza vaccines cannot be determined from clinical studies. here, we used the ferret model to address this for an avian influenza h5n1 vaccine. using oil-in-water adjuvants, we generated groups of ferrets with undetectable (geometric mean titer [gmt] < 10), low (gmt = 28.3), or high (gmt > 761.1) hemagglutination-inhibition (hai) titers to the a/viet nam/ ...201728303960
endothelial cell tropism is a determinant of h5n1 pathogenesis in mammalian species.the cellular and molecular mechanisms underpinning the unusually high virulence of highly pathogenic avian influenza h5n1 viruses in mammalian species remains unknown. here, we investigated if the cell tropism of h5n1 virus is a determinant of enhanced virulence in mammalian species. we engineered h5n1 viruses with restricted cell tropism through the exploitation of cell type-specific microrna expression by incorporating microrna target sites into the viral genome. restriction of h5n1 replicatio ...201728282445
shifting clade distribution, reassortment, and emergence of new subtypes of highly pathogenic avian influenza a(h5) viruses collected from vietnamese poultry from 2012 to 2015.whole-genome sequences of representative highly pathogenic avian influenza a(h5) viruses from vietnam were generated, comprising samples from poultry outbreaks and active market surveillance collected from january 2012 to august 2015. six hemagglutinin gene clades were characterized. clade 1.1.2 was predominant in southern mekong provinces throughout 2012 and 2013 but gradually disappeared and was not detected after april 2014. clade 2.3.2.1c viruses spread rapidly during 2012 and were detected ...201728003481
peromyscus as a model system for human hepatitis c: an opportunity to advance our understanding of a complex host parasite system.worldwide, there are 185 million people infected with hepatitis c virus and approximately 350,000 people die each year from hepatitis c associated liver diseases. human hepatitis c research has been hampered by the lack of an appropriate in vivo model system. most of the in vivo research has been conducted on chimpanzees, which is complicated by ethical concerns, small sample sizes, high costs, and genetic heterogeneity. the house mouse system has led to greater understanding of a wide variety o ...201727498234
genetic and physicochemical analyses of a novel ferret hepatitis e virus, and clinical signs of infection after birth.a novel cluster of five ferret hepatitis e virus (hev) strains was detected from nine laboratory ferrets (mustela putorius furo) imported from a ferret farm in the u.s. our detection of ferret hev rna and anti-hev antibodies, and alanine aminotransferase (alt) value assessment indicated that all of the 9 ferrets were infected with ferret hev, and that the infection exhibited three patterns: sub-clinical infection (n=2), acute hepatitis (n=6) and persistent infection (n=1). next-generation sequen ...201728347753
experimental hendra virus infection of dogs: virus replication, shedding and potential for transmission.characterisation of experimental hendra virus (hev) infection in dogs and assessment of associated transmission risk.201728124415
proliferative enteropathy caused by lawsonia intracellularis in chickens.proliferative enteropathy (pe) is an infectious disease caused by lawsonia intracellularis (li), an obligate intracellular bacterium. pe is endemic in swine herds and has been reported in a variety of mammals including horses, hamsters, rabbits, rats, guinea pigs, ferrets, foxes, dogs, sheep, deer and non-human primates. avian cases are reported only in ratite birds, including emus and ostriches. some studies show an absence of lawsonia spp. infection in chickens. in this study, we performed mor ...201728034455
lyssaviruses and rabies: current conundrums, concerns, contradictions and controversies.lyssaviruses are bullet-shaped, single-stranded, negative-sense rna viruses and the causative agents of the ancient zoonosis rabies. africa is the likely home to the ancestors of taxa residing within the genus lyssavirus, family rhabdoviridae. diverse lyssaviruses are envisioned as co-evolving with bats, as the ultimate reservoirs, over seemingly millions of years. in terms of relative distribution, overt abundance, and resulting progeny, rabies virus is the most successful lyssavirus species to ...201728299201
targeting alpha toxin to mitigate its lethal toxicity in ferret and rabbit models of staphylococcus aureus necrotizing pneumonia.the role broad-spectrum antibiotics play in the spread of antimicrobial resistance, coupled with their effect on the healthy microbiome, has led to advances in pathogen-specific approaches for the prevention or treatment of serious bacterial infections. one approach in clinical testing is passive immunization with a monoclonal antibody (mab) targeting alpha toxin for the prevention or treatment of staphylococcus aureus pneumonia. passive immunization with the human anti-alpha toxin mab, medi4893 ...201728115346
fleas of black-footed ferrets and their potential role in the movement of plague.sylvatic plague is one of the major impediments to the recovery of the black-footed ferret ( mustela nigripes ) because it decimates their primary prey species, prairie dogs ( cynomys spp.), and directly causes mortality in ferrets. fleas are the primary vector of yersinia pestis , the causative agent of sylvatic plague. the goal of this research was to better understand the flea fauna of ferrets and the factors that might influence flea abundance on ferrets. fleas from ferrets were tested for y ...201728384062
connexin36 expression in the mammalian retina: a multiple-species comparison.much knowledge about interconnection of human retinal neurons is inferred from results on animal models. likewise, there is a lack of information on human retinal electrical synapses/gap junctions (gj). connexin36 (cx36) forms gjs in both the inner and outer plexiform layers (ipl and opl) in most species including humans. however, a comparison of cx36 gj distribution in retinas of humans and popular animal models has not been presented. to this end a multiple-species comparison was performed in ...201728337128
novel urease-negative helicobacter sp. 'h. enhydrae sp. nov.' isolated from inflamed gastric tissue of southern sea otters.a total of 31 sea otters enhydra lutris nereis found dead or moribund (and then euthanized) were necropsied in california, usa. stomach biopsies were collected and transected with equal portions frozen or placed in formalin and analyzed histologically and screened for helicobacter spp. in gastric tissue. helicobacter spp. were isolated from 9 sea otters (29%); 58% (18 of 31) animals were positive for helicobacter by pcr. the helicobacter sp. was catalase- and oxidase-positive and urease-negative ...201728177288
exploiting interspecific olfactory communication to monitor predators.olfaction is the primary sense of many mammals and subordinate predators use this sense to detect dominant species, thereby reducing the risk of an encounter and facilitating coexistence. chemical signals can act as repellents or attractants and may therefore have applications for wildlife management. we devised a field experiment to investigate whether dominant predator (ferret mustela furo) body odor would alter the behavior of three common mesopredators: stoats (mustela erminea), hedgehogs (e ...201727983773
diagnosis and management of pyothorax in a domestic ferret (mustela putorius furo).to describe the diagnosis, management, and outcome of pyothorax in a domestic ferret (mustela putorius furo).201728485830
pathogenic analysis of the pandemic 2009 h1n1 influenza a viruses in ferrets.the pandemic 2009 h1n1 influenza a virus emerged in humans and caused the first influenza pandemic of the 21st century. mexican isolates, a/mexico/4108/2009 (h1n1) (mex4108) and a/mexico/indre4478/2009 (h1n1) (mex4487) derived from a mild case and from a cluster of severe cases, showed heterogeneity in virulence in a cynomolgus macaque model. to compare the more pathogenic differences, we generated recombinant viruses and compared their virulence in ferrets. ferrets infected with recombinant mex ...201728674309
neuraminidase-based recombinant virus-like particles protect against lethal avian influenza a(h5n1) virus infection in ferrets.avian influenza a (h5n1) viruses represent a growing threat for an influenza pandemic. the presence of widespread avian influenza virus infections further emphasizes the need for vaccine strategies for control of pre-pandemic h5n1 and other avian influenza subtypes. influenza neuraminidase (na) vaccines represent a potential strategy for improving vaccines against avian influenza h5n1 viruses. to evaluate a strategy for na vaccination, we generated a recombinant influenza virus-like particle (vl ...201728624679
stockpiled pre-pandemic h5n1 influenza virus vaccines with as03 adjuvant provide cross-protection from h5n2 clade 2.3.4.4 virus challenge in ferrets.avian influenza viruses, notably h5 subtype viruses, pose a continuous threat to public health due to their pandemic potential. in recent years, influenza virus h5 subtype split vaccines with novel oil-in-water emulsion based adjuvants (e.g. as03, mf59) have been shown to be safe, immunogenic, and able to induce broad immune responses in clinical trials, providing strong scientific support for vaccine stockpiling. however, whether such vaccines can provide protection from infection with emerging ...201728554058
a novel a(h7n2) influenza virus isolated from a veterinarian caring for cats in a new york city animal shelter causes mild disease and transmits poorly in the ferret model.in december 2016, a low-pathogenic avian influenza (lpai) a(h7n2) virus was identified to be the causative source of an outbreak in a cat shelter in new york city, which subsequently spread to multiple shelters in the states of new york and pennsylvania. one person with occupational exposure to infected cats became infected with the virus, representing the first lpai h7n2 virus infection in a human in north america since 2003. considering the close contact that frequently occurs between companio ...201728515300
development of clade-specific and broadly reactive live attenuated influenza virus vaccines against rapidly evolving h5 subtype viruses.we have developed pandemic live attenuated influenza vaccines (plaivs) against clade 1 h5n1 viruses on an ann arbor cold-adapted (ca) backbone that induced long-term immune memory. in 2015, many human infections caused by a new clade (clade 2.2.1.1) of goose/guangdong (gs/gd) lineage h5n1 viruses were reported in egypt, which prompted updating of the h5n1 plaiv. we explored two strategies to generate suitable plaivs. the first approach was to modify the hemagglutinin gene of a highly pathogenic ...201728490598
a formulated tlr7/8 agonist is a flexible, highly potent and effective adjuvant for pandemic influenza vaccines.since 1997, highly pathogenic avian influenza viruses of the h5n1 subtype have been transmitted from avian hosts to humans. the severity of h5n1 infection in humans, as well as the sporadic nature of h5n1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. an effective h5n1 vaccine must ultimately provide protection against viruses from diverse clades. toll-like receptor (tlr) agonist adjuvant formulations have a demonstrated ab ...201728429728
possible role of fish as transport hosts for dracunculus spp. larvae.to inform dracunculus medinensis (guinea worm) eradication efforts, we evaluated the role of fish as transport hosts for dracunculus worms. ferrets fed fish that had ingested infected copepods became infected, highlighting the importance of recommendations to cook fish, bury entrails, and prevent dogs from consuming raw fish and entrails.201728820381
immunization-elicited broadly protective antibody reveals ebolavirus fusion loop as a site of vulnerability.while neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. here, we describe an immunization-elicited macaque antibody (ca45) that clamps the internal fusion loop with the n terminus of the ebolavirus glycoproteins (gps) and potently neutralizes ebola, sudan, bundibugyo, and reston viruses. ca45, alone or in combination with an antibody that blocks receptor binding, provided full ...201728525756
antibodies from a human survivor define sites of vulnerability for broad protection against ebolaviruses.experimental monoclonal antibody (mab) therapies have shown promise for treatment of lethal ebola virus (ebov) infections, but their species-specific recognition of the viral glycoprotein (gp) has limited their use against other divergent ebolaviruses associated with human disease. here, we mined the human immune response to natural ebov infection and identified mabs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. these ...201728525755
nasal infection of enterovirus d68 leading to lower respiratory tract pathogenesis in ferrets (mustela putorius furo).data from ev-d68-infected patients demonstrate that pathological changes in the lower respiratory tract are principally characterized by severe respiratory illness in children and acute flaccid myelitis. however, lack of a suitable animal model for ev-d68 infection has limited the study on the pathogenesis of this critical pathogen, and the development of a vaccine. ferrets have been widely used to evaluate respiratory virus infections. in the current study, we used ev-d68-infected ferrets as a ...201728489053
nontoxic outer membrane vesicles efficiently increase the efficacy of an influenza vaccine in mice and ferrets.in this study, we developed a further-modified outer membrane vesicle (fmomv) from the δmsbb/δpagp mutant of escherichia coli transformed with the plasmid, plpxf, in order to use it as an adjuvant for pandemic h1n1 (ph1n1) influenza vaccine. we evaluated the efficacy of the ph1n1 influenza vaccine containing the fmomv in animal models as compared to the commercial adjuvants, alum or addavax(tm). the fmomv-adjuvanted ph1n1 influenza vaccine induced a significant increase in the humoral immunity; ...201728576571
evaluation of the biological properties and cross-reactive antibody response to h10 influenza viruses in ferrets.the recent outbreak of avian origin h10n7 influenza among seals in northern europe, and two fatal human infections with an avian h10n8 virus in china, have demonstrated that h10 viruses can spread between mammals and cause severe disease in humans. to gain insight into the potential for h10 viruses to cross the species barrier and identify a candidate vaccine strain, we evaluated the in vitro and in vivo properties and antibody response in ferrets to 20 diverse h10 viruses. h10 virus infection o ...201728701401
preclinical and clinical demonstration of immunogenicity by mrna vaccines against h10n8 and h7n9 influenza viruses.recently, the world health organization confirmed 120 new human cases of avian h7n9 influenza in china resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. production speed and scale of mrna-based vaccines make them ideally suited to impede potential pandemic threats. here we show that lipid nanoparticle (lnp)-formulated, modified mrna vaccines, encoding hemagglutinin (ha) proteins of h10n8 (a/j ...201728457665
novel hemagglutinin nanoparticle influenza vaccine with matrix-m™ adjuvant induces hemagglutination inhibition, neutralizing, and protective responses in ferrets against homologous and drifted a(h3n2) subtypes.influenza viruses frequently acquire mutations undergoing antigenic drift necessitating annual evaluation of vaccine strains. highly conserved epitopes have been identified in the hemagglutinin (ha) head and stem regions, however, current influenza vaccines induce only limited responses to these conserved sites. here, we describe a novel seasonal recombinant ha nanoparticle influenza vaccine (niv) formulated with a saponin-based adjuvant, matrix-m™. niv induced hemagglutination inhibition (hai) ...201728844407
zoonotic risk, pathogenesis, and transmission of avian-origin h3n2 canine influenza virus.two subtypes of influenza a virus (iav), avian-origin canine influenza virus h3n2 (civ-h3n2) and equine-origin civ-h3n8, are enzootic in the canine population. dogs have demonstrated seroconversion to diverse iavs and naturally occurring reassortants of civ-h3n2 and the 2009 h1n1 pandemic virus (pdmh1n1) have been isolated. we conducted a thorough phenotypic evaluation of civ-h3n2 in order to assess its threat to human health. using ferret-generated antisera we determined that civ-h3n2 is antige ...201728814512
m2sr, a novel live influenza vaccine, protects mice and ferrets against highly pathogenic avian influenza.the emergence of highly pathogenic avian influenza h5n1 viruses has heightened global concern about the threat posed by pandemic influenza. to address the need for a highly effective universal influenza vaccine, we developed a novel m2-deficient single replication (m2sr) influenza vaccine virus and previously reported that it provided strong heterosubtypic protection against seasonal influenza viruses in mice. in the current study, we assessed m2sr induced protection against h5n1 influenza in mi ...201728668565
in vitro and in vivo evidence of a potential a(h1n1)pdm09 antigenic drift mediated by escape mutations in the haemagglutinin sa antigenic site.influenza a(h1n1)pdm09 virus continues to circulate worldwide without evidence of significant antigenic drift between 2009 and 2016. by using escape mutants, we previously identified six haemagglutinin (ha) changes (t80r, g143e, g158e, n159d, k166e and a198e) that were located within antigenic sites. combinations of these mutations were introduced into the a(h1n1)pdm09 ha plasmid by mutagenesis. reassortant 6 : 2 viruses containing both the ha and na genes of the a(h1n1)pdm09 and the six interna ...201728631598
inhibition of the infectivity and inflammatory response of influenza virus by arbidol hydrochloride in vitro and in vivo (mice and ferret).influenza virus infections are the main contagious respiratory disease with high levels of morbidity and mortality worldwide. antiviral drugs are indispensable for the prophylaxis and treatment of influenza and other respiratory viral infections. in this study, the arbidol hydrochloride (arb), which has been licensed in russia and china, is used to investigate its anti-viral and anti-inflammatory efficacy in vitro and in vivo. the antiviral results in vitro showed that arb had a better inhibitio ...201728475918
intravenous immunoglobulin protects against severe pandemic influenza infection.influenza is a highly contagious, acute, febrile respiratory infection that can have fatal consequences particularly in individuals with chronic illnesses. sporadic reports suggest that intravenous immunoglobulin (ivig) may be efficacious in the influenza setting. we investigated the potential of human ivig to ameliorate influenza infection in ferrets exposed to either the pandemic h1n1/09 virus (ph1n1) or highly pathogenic avian influenza (h5n1). ivig administered at the time of influenza virus ...201728408242
pathogenicity and transmission of a swine influenza a(h6n6) virus.subtype h6 influenza a viruses (iavs) are commonly detected in wild birds and domestic poultry and can infect humans. in 2010, a h6n6 virus emerged in southern china, and since then, it has caused sporadic infections among swine. we show that this virus binds to α2,6-linked and α2,3-linked sialic acids. mutations at residues 222 (alanine to valine) and 228 (glycine to serine) of the virus hemagglutinin (ha) affected its receptor-binding properties. experiments showed that the virus has limited t ...201728400591
an amino acid in the stalk domain of n1 neuraminidase is critical for enzymatic activity.neuraminidase (na) is a sialidase expressed on the surface of influenza a viruses that releases progeny viruses from the surface of infected cells and prevents viruses becoming trapped in mucus. it is a homotetramer, with each monomer consisting of a transmembrane region, a stalk, and a globular head with sialidase activity. we recently characterized two swine viruses of the pandemic h1n1 lineage, a/swine/virginia/1814-1/2012 (ph1n1low-1) and a/swine/virginia/1814-2/2012 (ph1n1low-2), with almos ...201727847354
permissivity of dpp4 orthologs to mers-coronavirus is governed by glycosylation and other complex determinants.middle east respiratory syndrome coronavirus (mers-cov) utilizes dipeptidyl peptidase 4 (dpp4) as an entry receptor. while bat, camel, and human dpp4 support mers-cov infection, several dpp4 orthologs, including mouse, ferret, hamster, and guinea pig, do not. previous work revealed that glycosylation of mouse dpp4 plays a role in blocking mers-cov infection. here, we test whether glycosylation also acts as a determinant of permissivity for ferret, hamster, and guinea pig dpp4. we find that while ...201728747502
mutations driving airborne transmission of a/h5n1 virus in mammals cause substantial attenuation in chickens only when combined.a/h5n1 influenza viruses pose a threat to human and animal health. a fully avian a/h5n1 influenza virus was previously shown to acquire airborne transmissibility between ferrets upon accumulation of five or six substitutions that affected three traits: polymerase activity, hemagglutinin stability and receptor binding. here, the impact of these traits on a/h5n1 virus replication, tissue tropism, pathogenesis and transmission was investigated in chickens. the virus containing all substitutions ass ...201728775271
the hemagglutinin a stem antibody medi8852 prevents and controls disease and limits transmission of pandemic influenza viruses.medi8852 is a novel monoclonal antibody (mab) that neutralizes both group i and group ii influenza a viruses (iavs) in vitro. we evaluated whether medi8852 was effective for prophylaxis and therapy against representative group i (h5n1) and group ii (h7n9) pandemic iavs in mice and ferrets and could be used to block transmission of influenza h1n1pdm09 in ferrets, compared to an irrelevant control mab r347 and oseltamivir.201728633457
enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza a h5n1 viruses in ferrets.sporadic avian to human transmission of highly pathogenic avian influenza (hpai) a(h5n1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. following the spread and sustained circulation of clade 2 viruses across multiple continents, numerous subclades and genotypes have been described. to better understand the pathogenesis associated with the continued diversification of clade 2a(h5n1) influenza viruses, we investigated the relative vi ...201728038412
pathogenicity testing of influenza candidate vaccine viruses in the ferret model.the development of influenza candidate vaccine viruses (cvvs) for pre-pandemic vaccine production represents a critical step in pandemic preparedness. the multiple subtypes and clades of avian or swine origin influenza viruses circulating world-wide at any one time necessitates the continuous generation of cvvs to provide an advanced starting point should a novel zoonotic virus cross the species barrier and cause a pandemic. furthermore, the evolution and diversity of novel influenza viruses tha ...201728846898
influenza-omics and the host response: recent advances and future prospects.influenza a viruses (iav) continually evolve and have the capacity to cause global pandemics. because iav represents an ongoing threat, identifying novel therapies and host innate immune factors that contribute to iav pathogenesis is of considerable interest. this review summarizes the relevant literature as it relates to global host responses to influenza infection at both the proteome and transcriptome level. the various-omics infection systems that include but are not limited to ferrets, mice ...201728604586
assessment of pathogenicity and antigenicity of american lineage influenza h5n2 viruses in taiwan.during december 2003 and march 2004, large scale epidemics of low-pathogenic avian influenza (lpai) h5n2 occurred in poultry farms in central and southern taiwan. based on genomic analysis, these h5n2 viruses contain ha and na genes of american-lineage h5n2 viruses and six internal genes from avian influenza a/h6n1 viruses endemic in poultry in taiwan. after disappearing for several years, these novel influenza h5n2 viruses caused outbreaks in poultry farms again in 2008, 2010 and 2012, and have ...201728549236
carbohydrate fatty acid monosulphate esters are safe and effective adjuvants for humoral responses.carbohydrate fatty acid sulphate esters (cfases) formulated in a squalane-in-water emulsion are effective adjuvants for humoral responses to a wide range of antigens in various animal species but rise in body temperature and local reactions albeit mild or minimal hampers application in humans. in rabbits, body temperature increased 1°c one day after intramuscular (im) injection, which returned to normal during the next day. the effect increased with increasing dose of cfase but not with the numb ...201728479181
replication of h9 influenza viruses in the human ex vivo respiratory tract, and the influence of neuraminidase on virus release.h9n2 viruses are the most widespread influenza viruses in poultry in asia. we evaluated the infection and tropism of human and avian h9 influenza virus in the human respiratory tract using ex vivo respiratory organ culture. h9 viruses infected the upper and lower respiratory tract and the majority of h9 viruses had a decreased ability to release virus from the bronchus rather than the lung. this may be attributed to a weak neuraminidase (na) cleavage of carbon-6-linked sialic acid (sia) rather t ...201728740108
antiviral drug-resistant influenza b viruses carrying h134n substitution in neuraminidase, laos, february 2016.in february 2016, three influenza b/victoria/2/87 lineage viruses exhibiting 4- to 158-fold reduced inhibition by neuraminidase inhibitors were detected in laos. these viruses had an h134n substitution in the neuraminidase and replicated efficiently in vitro and in ferrets. current antiviral drugs may be ineffective in controlling infections caused by viruses harboring this mutation.201728322707
circulation of influenza b lineages in northern viet nam, 2007-2014.influenza b viruses circulate throughout viet nam, and their activities vary by region. there have been two antigenically distinct lineages of influenza b viruses co-circulating in the past 20 years; however, only one lineage is selected as a component of contemporary trivalent seasonal influenza vaccines. to improve the understanding of circulating influenza b lineages and influenza vaccine mismatches, we report the virus lineages circulating in northern viet nam over an eight-year period (2007 ...201726798557
modified vaccinia virus ankara preferentially targets antigen presenting cells in vitro, ex vivo and in vivo.modified vaccinia virus ankara (mva) is a promising vaccine vector with an excellent safety profile. however, despite extensive pre-clinical and clinical testing, surprisingly little is known about the cellular tropism of mva, especially in relevant animal species. here, we performed in vitro, ex vivo and in vivo experiments with recombinant mva expressing green fluorescent protein (rmva-gfp). in both human peripheral blood mononuclear cells and mouse lung explants, rmva-gfp predominantly infect ...201728819261
transmission of mycobacterium xenopi to a pet albino ferret (mustela putorius furo) from a domestic aquarium.a three-year-old ferret presented with a three-month history of rapid clinical deterioration necessitating euthanasia shortly after initial veterinary assessment. postmortem pcr testing confirmed mycobacterium xenopi which is most commonly identified in amphibians, reptiles and aquatic life. infection of a captive-bred domestic ferret is highly unusual. a collaborative effort involving medical doctors, clinical veterinarians and veterinary pathologists investigated the potential sources of human ...201728774941
unexpected detection of porcine rotavirus c strains carrying human origin vp6 gene.rotavirus c (rvc), a known etiological agent of diarrheal outbreaks, mainly inflicts swine population globally with sporadic incidence in human, cattle, ferret, mink and dog.201728643555
burrow dusting or oral vaccination prevents plague-associated prairie dog colony collapse.plague impacts prairie dogs (cynomys spp.), the endangered black-footed ferret (mustela nigripes) and other sensitive wildlife species. we compared efficacy of prophylactic treatments (burrow dusting with deltamethrin or oral vaccination with recombinant "sylvatic plague vaccine" [rcn-f1/v307]) to placebo treatment in black-tailed prairie dog (c. ludovicianus) colonies. between 2013 and 2015, we measured prairie dog apparent survival, burrow activity and flea abundance on triplicate plots ("bloc ...201728643090
characterization of sudan ebolavirus infection in ferrets.sudan virus (sudv) outbreaks in africa are highly lethal; however, the development and testing of novel antivirals and vaccines for this virus has been limited by a lack of suitable animal models. non-human primates (nhp) remain the gold standard for modeling filovirus disease, but they are not conducive to screening large numbers of experimental compounds and should only be used to test the most promising candidates. therefore, other smaller animal models are a valuable asset. we have recently ...201728545034
analysis of zp1 gene reveals differences in zona pellucida composition in carnivores.the zona pellucida (zp) is an extracellular envelope that surrounds mammalian oocytes. this coat participates in the interaction between gametes, induction of the acrosome reaction, block of polyspermy and protection of the oviductal embryo. previous studies suggested that carnivore zp was formed by three glycoproteins (zp2, zp3 and zp4), with zp1 being a pseudogene. however, a recent study in the cat found that all four proteins were expressed. in the present study, in silico and molecular anal ...201728679462
biobanking efforts and new advances in male fertility preservation for rare and endangered species.understanding and sustaining biodiversity is a multi-disciplinary science that benefits highly from the creation of organized and accessible collections of biomaterials (genome resource banks). large cryo-collections are invaluable tools for understanding, cataloging, and protecting the genetic diversity of the world's unique animals and plants. specifically, the systematic collection and preservation of semen from rare species has been developed significantly in recent decades with some biobank ...201725966625
pulse of inflammatory proteins in the pregnant uterus of european polecats (mustela putorius) leading to the time of implantation.uterine secretory proteins protect the uterus and conceptuses against infection, facilitate implantation, control cellular damage resulting from implantation, and supply pre-implantation embryos with nutrients. unlike in humans, the early conceptus of the european polecat (mustela putorius; ferret) grows and develops free in the uterus until implanting at about 12 days after mating. we found that the proteins appearing in polecat uteri changed dramatically with time leading to implantation. seve ...201728405395
regional distribution of cholinergic, catecholaminergic, serotonergic and orexinergic neurons in the brain of two carnivore species: the feliform banded mongoose (mungos mungo) and the caniform domestic ferret (mustela putorius furo).the nuclear organization of the cholinergic, catecholaminergic, serotonergic and orexinergic neurons in the brains of two species of carnivore, the banded mongoose (mungos mungo) and domestic ferret (mustela putorius furo), is presented. the banded mongoose belongs to the feliform suborder and the domestic ferret to the caniform suborder, having last shared a common ancestor approximately 53 million years ago; however, they have a very similar overall morphology and life history, presenting an i ...201728416460
vaccines for conservation: plague, prairie dogs & black-footed ferrets as a case study.the endangered black-footed ferret (mustela nigripes) is affected by plague, caused by yersinia pestis, both directly, as a cause of mortality, and indirectly, because of the impacts of plague on its prairie dog (cynomys spp.) prey base. recent developments in vaccines and vaccine delivery have raised the possibility of plague control in prairie dog populations, thereby protecting ferret populations. a large-scale experimental investigation across the western us shows that sylvatic plague vaccin ...201728879613
hodgkin's-like lymphoma in a ferret (mustela putorius furo).a 7-year-old castrated male ferret developed unilateral cervical lymphadenomegaly over a 1-month period. histological examination revealed proliferation of tumor cells in a diffuse and partially nodular pattern. the tumor cells were predominantly hodgkin cells and binucleated reed-sternberg cells, characterized by abundant, clear, vacuolated cytoplasm, pleomorphic, ovoid nuclei with thick nuclear membranes and distinct nucleoli. multinucleated cells, resembling lymphocytic and histiocytic (l&h) ...201728804091
diagnosis and treatment of esophageal foreign body or stricture in three ferrets (mustela putorius furo).case description 3 ferrets (mustela putorius furo), aged 1 to 2 years, were referred for evaluation of a 4-day to 2-week history of gastrointestinal signs, including anorexia, regurgitation, and vomiting. clinical findings all 3 ferrets had clinical signs suggestive of dysphagia or esophagitis on initial examination. esophagoscopy, barium-contrast esophagography, or both revealed foreign bodies with mucosal inflammation in 1 patient and an esophageal foreign body with stricture in 2 patients. on ...201728763273
molecular investigations of development and diseases of the brain of higher mammals using the ferret.the brains of higher mammals such as primates and carnivores contain well-developed unique brain structures. uncovering the physiological functions, developmental mechanisms and evolution of these brain structures would greatly facilitate our understanding of the human brain and its diseases. although the anatomical and electrophysiological features of these brain structures have been intensively investigated, our knowledge about their molecular bases is still limited. to overcome this limitatio ...201728496051
delineating morbillivirus entry, dissemination and airborne transmission by studying in vivo competition of multicolor canine distemper viruses in ferrets.identification of cellular receptors and characterization of viral tropism in animal models have vastly improved our understanding of morbillivirus pathogenesis. however, specific aspects of viral entry, dissemination and transmission remain difficult to recapitulate in animal models. here, we used three virologically identical but phenotypically distinct recombinant (r) canine distemper viruses (cdv) expressing different fluorescent reporter proteins for in vivo competition and airborne transmi ...201728481926
pneumatosis coli in a domestic ferret (mustela putorius furo).a 4-year-old spayed female ferret was presented with acute diarrhea and partial anorexia. pneumatosis coli and segmental enteropathy were identified by ultrasonography and radiography. fecal culture did not identify any pathogenic bacteria. medical management of concurrent diseases and antibiotic therapy resulted in resolution of clinical signs and pneumatosis coli.201728373731
generation of monoclonal antibodies against immunoglobulin proteins of the domestic ferret (mustela putorius furo).the domestic ferret (mustela putorius furo) serves as an animal model for the study of several viruses that cause human disease, most notably influenza. despite the importance of this animal model, characterization of the immune response by flow cytometry (fcm) is severely hampered due to the limited number of commercially available reagents. to begin to address this unmet need and to facilitate more in-depth study of ferret b cells including the identification of antibody-secreting cells, eight ...201728286781
cold exposure down-regulates immune response pathways in ferret aortic perivascular adipose tissue.perivascular adipose tissue (pvat) surrounds blood vessels and releases paracrine factors, such as cytokines, which regulate local inflammation. the inflammatory state of pvat has an important role in vascular disease; a pro-inflammatory state has been related with atherosclerosis development, whereas an anti-inflammatory one is protective. cold exposure beneficially affects immune responses and, could thus impact the pathogenesis of cardiovascular diseases. in this study, we investigated the ef ...201728251235
invasive histiocytic sarcoma of the lumbar spine in a ferret (mustela putorius furo).this report describes the history, clinical examination and histopathology of a histiocytic sarcoma in a domestic ferret. clinical signs were acute paraplegia and dysuria. physical examination revealed a firm, smooth, touch-sensitive mass in and around the lumbar vertebral column. neurologic examination was consistent with a lesion between spinal cord segments t3 and l3. magnetic resonance images revealed bone lesions of l2 and l3 combined with compression of the spinal cord due to a homogenous, ...201728160308
ferret oncology: diseases, diagnostics, and therapeutics.neoplastic disease is common in ferrets. approximately half of all tumors diagnosed in ferrets are located in the endocrine or hemolymphatic system. many factors may influence the choice of treatment. medical management of adrenal tumors has a greater disease-free period compared to adrenalectomy. in ferrets with an insulinoma, no difference is seen in the mean survival time of medically and surgically treated patients. aside from medical and surgical treatment modalities, chemotherapy and radia ...201727890288
imaging diagnosis-radiography and ultrasonography of bilateral congenital ureterovesical junction stenosis causing hydronephrosis and hydroureter in a ferret (mustela putorius furo).an 8-month-old neutered male ferret was presented for vaccination and preventive treatment for adrenal gland disease. abdominal ultrasound revealed severe bilateral hydronephrosis and hydroureter. excretory urography and negative contrast cystography showed bilateral ureterovesical junction stenosis. positive retrograde cystography demonstrated right ureteral reflux. a subcutaneous ureteral bypass was placed in the left kidney; however, it had to be removed 3 months later due to an obstruction a ...201727490371
lachrymal gland basal cell adenocarcinoma in a ferret (mustela putorius furo).a 1 cm diameter mass was detected in the caudal superotemporal area of the left eye of a 6-year-old neutered male ferret (mustela putorius furo). the mass and the left eye were removed surgically. microscopical examination revealed a tumour of the adnexal gland of the eye that had invaded the surrounding ocular muscle. the tumour was composed of basal-type epithelial cells arranged in a solid, or occasionally tubular, pattern. immunohistochemically, the tumour cells expressed cytokeratin and p63 ...201727388784
distribution of o-acetylated sialic acids among target host tissues for influenza virus.sialic acids (sias) are important glycans displayed on the cells and tissues of many different animals and are frequent targets for binding and modification by pathogens, including influenza viruses. influenza virus hemagglutinins bind sias during the infection of their normal hosts, while the encoded neuraminidases and/or esterases remove or modify the sia to allow virion release or to prevent rebinding. sias naturally occur in a variety of modified forms, and modified sias can alter influenza ...201728904995
adaptive mutations of neuraminidase stalk truncation and deglycosylation confer enhanced pathogenicity of influenza a viruses.it has been noticed that neuraminidase (na) stalk truncation has arisen from evolutionary adaptation of avian influenza a viruses (iavs) from wild aquatic birds to domestic poultry. we identified this molecular alteration after the adaptation of a 2009 pandemic h1n1 virus (ph1n1) in balb/c mice. the mouse-adapted ph1n1 lost its eight consecutive amino acids including one potential n-linked glycosite from the na stalk region. to explore the relationship of na stalk truncation or deglycosylation w ...201728883554
molecular basis of mammalian transmissibility of avian h1n1 influenza viruses and their pandemic potential.north american wild birds are an important reservoir of influenza a viruses, yet the potential of viruses in this reservoir to transmit and cause disease in mammals is not well understood. our surveillance of avian influenza viruses (aivs) at delaware bay, usa, revealed a group of similar h1n1 aivs isolated in 2009, some of which were airborne-transmissible in the ferret model without prior adaptation. comparison of the genomes of these viruses revealed genetic markers of airborne transmissibili ...201728874549
altered virulence of highly pathogenic avian influenza (hpai) h5n8 reassortant viruses in mammalian models.recently identified highly pathogenic avian influenza (hpai) h5n8 viruses (clade 2.3.4.4) are relatively low to moderately pathogenic in mammalian hosts compared to hpai h5n1 viruses. in this study, we generated reassortant viruses comprised of a/md/korea/w452/2014(h5n8) with substitution of individual genes from a/em/korea/w149/2006(h5n1) to understand the contribution of each viral gene to virulence in mammals. substituting the pb2 gene segment or the na gene segment of the h5n8 virus by that ...201728873012
specific features of the hypothalamic leptin signaling response to cold exposure are reflected in peripheral blood mononuclear cells in rats and ferrets.objectives: cold exposure induces hyperphagia to counteract fat loss related to lipid mobilization and thermogenic activation. the aim of this study was investigate on the molecular mechanisms involved in cold-induced compensatory hyperphagia. methods: we analyzed the effect of cold exposure on gene expression of orexigenic and anorexigenic peptides, and of leptin signaling-related genes in the hypothalamus of rats at different ages (1, 2, 4, and 6 months), as well as in ferrets. we also evaluat ...201728860997
folding of the cerebral cortex requires cdk5 in upper-layer neurons in gyrencephalic mammals.folds in the cerebral cortex in mammals are believed to be key structures for accommodating increased cortical neurons in the cranial cavity. however, the mechanisms underlying cortical folding remain largely unknown, mainly because genetic manipulations for the gyrencephalic brain have been unavailable. by combining in utero electroporation and the crispr/cas9 system, we succeeded in efficient gene knockout of cdk5, which is mutated in some patients with classical lissencephaly, in the gyrencep ...201728854363
dynamic reconfiguration of cortical functional connectivity across brain states.throughout each day, the brain displays transient changes in state, as evidenced by shifts in behavior and vigilance. while the electrophysiological correlates of brain states have been studied for some time, it remains unclear how large-scale cortico-cortical functional connectivity systematically reconfigures across states. here, we investigate state-dependent shifts in cortical functional connectivity by recording local field potentials (lfps) during spontaneous behavioral transitions in the ...201728821753
determination of ferret enteric coronavirus genome in laboratory ferrets.ferret enteric coronavirus (frecv) rna was detected in laboratory ferrets. analysis of the complete genome sequence of 2 strains, frcov4370 and frcov063, revealed that frecv shared 49.9%-68.9% nucleotide sequence identity with known coronaviruses. these results suggest that frecv might be classified as a new species in the genus alphacoronavirus.201728820366
evidence-based advances in ferret medicine.this literature review covers approximately 35 years of veterinary medicine. this article develops the current state of knowledge in pet ferret medicine regarding the most common diseases according to evidence-based data and gives insight into further axis of research. literature review was conducted through identification of keywords (title + ferret) with web-based database searching. to appreciate the methodological quality and the level of evidence of each article included in the review, full ...201728781033
retrospective investigation of cardiopulmonary resuscitation outcome in 146 exotic animals.the outcomes of cardiopulmonary resuscitation (cpr) were retrospectively evaluated in 146 exotic animals including 20 pet birds, 47 rabbits, 34 hamsters, 18 ferrets, 7 turtles, and 20 other small mammals in cardiopulmonary arrest (cpa) at presentation or during hospitalization at an animal clinic. the rates of return of spontaneous circulation, survival after cpr, and discharge were 9.3%, 2.3%, and 1.2%, respectively. the mean success rate of cpr in animals included in this study was lower than ...201728757521
effect of the camelid's seminal plasma ovulation-inducing factor/β-ngf: a kisspeptin target hypothesis.female mammals are classified into spontaneous and induced ovulators based on the mechanism eliciting ovulation. ovulation in spontaneous species (e.g., human, sheep, cattle, horse, pigs, and most rodents) occurs at regular intervals and depends upon the circulating estradiol. however, in induced ovulators (e.g., rabbits, ferrets, cats, and camelids), ovulation is associated with coitus. in the later, various factors have been proposed to trigger ovulation, including auditory, visual, olfactory, ...201728713816
ultrasonographic features of insulinoma in six ferrets.insulinoma is a functional, insulin-secreting tumor, arising from the beta islet cells of the pancreas. it is one of the most common neoplasms in ferrets and has been associated with clinical signs of hypoglycemia, such as ptyalism, pawing at the mouth, seizures, lethargy, and coma. the ultrasonographic features of insulinoma in ferrets have not been previously reported. the purpose of this retrospective case series study was to describe the ultrasonographic features of confirmed insulinoma in a ...201728699200
corticogeniculate feedback sharpens the temporal precision and spatial resolution of visual signals in the ferret.the corticogeniculate (cg) pathway connects the visual cortex with the visual thalamus (lgn) in the feedback direction and enables the cortex to directly influence its own input. despite numerous investigations, the role of this feedback circuit in visual perception remained elusive. to probe the function of cg feedback in a causal manner, we selectively and reversibly manipulated the activity of cg neurons in anesthetized ferrets in vivo using a combined viral-infection and optogenetics approac ...201728698363
expanding access to care: scope of practice laws.allied health professionals play an integral role in providing safe, affordable care to communities in need. laws that define the permissible scope of practice for these professionals may take full advantage of these providers and may unnecessarily restrict safe and effective care. nurse practitioners in many states may provide care independent of a physician; research reveals that this care is safe, affordable and accessible. yet hurdles exist that prevent communities from securing the full ben ...201728661304
improved growth patterns in cystic fibrosis mice after loss of histone deacetylase 6.growth failure in cystic fibrosis (cf) patients has been well-documented and shown to correlate with poorer disease outcomes. this observation is also true in cf animal models, including mouse, pig, rat, and ferret. the etiology underlying growth deficits is unknown, and our previous work demonstrated reduced tubulin acetylation in cf cell models and tissue that is correctable by inhibition of histone deacetylase-6 (hdac6). here, we hypothesize that loss of hdac6 will improve growth phenotype in ...201728623308
egocentric and allocentric representations in auditory cortex.a key function of the brain is to provide a stable representation of an object's location in the world. in hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system, and auditory cortex is necessary for sound localization. however, the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) ...201728617796
breakdown of local information processing may underlie isoflurane anesthesia effects.the disruption of coupling between brain areas has been suggested as the mechanism underlying loss of consciousness in anesthesia. this hypothesis has been tested previously by measuring the information transfer between brain areas, and by taking reduced information transfer as a proxy for decoupling. yet, information transfer is a function of the amount of information available in the information source-such that transfer decreases even for unchanged coupling when less source information is ava ...201728570661
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