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https://www.readbyqxmd.com/read/28931216/emergence-of-oseltamivir-resistant-h7n9-influenza-viruses-in-immunosuppressed-cynomolgus-macaques
#1
Maki Kiso, Kiyoko Iwatsuki-Horimoto, Seiya Yamayoshi, Ryuta Uraki, Mutsumi Ito, Noriko Nakajima, Shinya Yamada, Masaki Imai, Eiryo Kawakami, Yuriko Tomita, Satoshi Fukuyama, Yasushi Itoh, Kazumasa Ogasawara, Tiago J S Lopes, Tokiko Watanabe, Louise H Moncla, Hideki Hasegawa, Thomas C Friedrich, Gabriele Neumann, Yoshihiro Kawaoka
Antiviral compounds (eg, the neuraminidase inhibitor oseltamivir) are invaluable for the treatment of individuals infected with influenza A viruses of the H7N9 subtype (A[H7N9]), which have infected and killed hundreds of persons. However, oseltamivir treatment often leads to the emergence of resistant viruses in immunocompromised individuals. To better understand the emergence and properties of oseltamivir-resistant A(H7N9) viruses in immunosuppressed individuals, we infected immunosuppressed cynomolgus macaques with an A(H7N9) virus and treated them with oseltamivir...
September 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28929521/safety-tolerability-and-pharmacokinetics-of-radavirsen-avi-7100-an-antisense-oligonucleotide-targeting-influenza-a-m1-m2-translation
#2
John H Beigel, Jocelyn Voell, Paula Muñoz, Parag Kumar, Kristina M Brooks, Jianbo Zhang, Patrick Iversen, Alison Heald, Michael Wong, Richard T Davey
AIMS: To assess the safety, tolerability, and pharmacokinetics (PK) of radavirsen following single ascending doses and multiple doses given as IV infusions in healthy adults. METHODS: A Phase 1 safety and pharmacokinetic (PK) study of radavirsen was performed in healthy volunteers. The study was divided into 2 parts. The first was a single-ascending dose study of 5 cohorts of 8 subjects each, randomized 6:2 to receive single intravenous doses of radavirsen ranging from 0...
September 20, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28922855/a%C3%A2-complex-code-of-extrinsic-influences-on-cortical-progenitor-cells-of-higher-mammals
#3
Isabel Reillo, Camino de Juan Romero, Adrián Cárdenas, Francisco Clascá, Maria Ángeles Martínez-Martinez, Víctor Borrell
Development of the cerebral cortex depends critically on the regulation of progenitor cell proliferation and fate. Cortical progenitor cells are remarkably diverse with regard to their morphology as well as laminar and areal position. Extrinsic factors, such as thalamic axons, have been proposed to play key roles in progenitor cell regulation, but the diversity, extent and timing of interactions between extrinsic elements and each class of cortical progenitor cell in higher mammals remain undefined. Here we use the ferret to demonstrate the existence of a complex set of extrinsic elements that may interact, alone or in combination, with subpopulations of progenitor cells, defining a code of extrinsic influences...
September 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28918695/large-animal-models-of-traumatic-brain-injury
#4
Jun-Xi Dai, Yan-Bin Ma, Nan-Yang Le, Jun Cao, Yang Wang
Traumatic brain injury (TBI) is a devastating and common health problem in today's society. Relevant animal models of TBI provide powerful tools to study TBI in a controlled, rigorous and cost-efficient manner. The mostly used animals in TBI studies so far are rodents, however, huge inter-species differences in anatomy, morphology, metabolism, neurobiology, and lifespan between rodents and humans have impeded the translation of research findings from labs to human. Compared with rodents, large animals (eg. swine, rabbit, sheep, ferret) show great advantages in modelling TBI due to the similarity of their brains to human brain...
September 18, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28917826/potassic-zeolites-from-brazilian-coal-ash-for-use-as-a-fertilizer-in-agriculture
#5
Camila Gomes Flores, Helena Schneider, Nilson Romeu Marcilio, Lizete Ferret, João Carlos Pinto Oliveira
Brazilian coal has an ash content ranging from 30 to 50% by weight. Consequently, its use in coal-fired thermoelectric for power production generates a lot of waste. The construction sector is the largest consumer of coal ash, but it cannot absorb the entire amount generated. Thus, other applications for coal ash should be studied in aim to optimize the use of this industrial waste. This research had as focus to synthesize potassic zeolite from of the coal ash into on potassium fertilizer for the grown wheat plant...
September 13, 2017: Waste Management
https://www.readbyqxmd.com/read/28904995/distribution-of-o-acetylated-sialic-acids-among-target-host-tissues-for-influenza-virus
#6
Brian R Wasik, Karen N Barnard, Robert J Ossiboff, Zahra Khedri, Kurtis H Feng, Hai Yu, Xi Chen, Daniel R Perez, Ajit Varki, Colin R Parrish
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 virus host tropisms through their altered interactions with the viral glycoproteins...
September 2017: MSphere
https://www.readbyqxmd.com/read/28888734/influence-of-the-container-on-the-consumption-of-cosmetic-products
#7
M P Gomez-Berrada, A S Ficheux, M Galonnier, J E Rolfo, A Rielland, S Guillou, D De Javel, A C Roudot, P J Ferret
The container, also known as primary package or inner package, could be defined as the packaging designed to come into direct contact with the cosmetic product. To author's knowledge, no study was available regarding the effect of the primary package on the consumption of cosmetic products. The aim of the study was to assess the impact of the container on the consumption of three cosmetic products widely used, i.e. shampoo, shower gel and emollient cream. The three products were contained in a tube with a flip top cap and in a bottle with a pump...
September 6, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28883554/adaptive-mutations-of-neuraminidase-stalk-truncation-and-deglycosylation-confer-enhanced-pathogenicity-of-influenza-a-viruses
#8
Sehee Park, Jin Il Kim, Ilseob Lee, Joon-Yong Bae, Kirim Yoo, Misun Nam, Juwon Kim, Mee Sook Park, Ki-Joon Song, Jin-Won Song, Sun-Ho Kee, Man-Seong Park
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 with viral pathogenicity changes, we generated NA stalk mutant viruses on the pH1N1 backbone by reverse genetics...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28879613/vaccines-for-conservation-plague-prairie-dogs-black-footed-ferrets-as-a-case-study
#9
Daniel J Salkeld
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 vaccine delivered in oral baits can increase prairie dog survival...
September 6, 2017: EcoHealth
https://www.readbyqxmd.com/read/28874549/molecular-basis-of-mammalian-transmissibility-of-avian-h1n1-influenza-viruses-and-their-pandemic-potential
#10
Mark Zanin, Sook-San Wong, Subrata Barman, Challika Kaewborisuth, Peter Vogel, Adam Rubrum, Daniel Darnell, Atanaska Marinova-Petkova, Scott Krauss, Richard J Webby, Robert G Webster
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 transmissibility in the Polymerase Basic 2 (PB2), PB1, PB1-F2, Polymerase Acidic-X (PA-X), Nonstructural Protein 1 (NS1), and Nuclear Export Protein (NEP) genes...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28873012/altered-virulence-of-highly-pathogenic-avian-influenza-hpai-h5n8-reassortant-viruses-in-mammalian-models
#11
Su-Jin Park, Eun-Ha Kim, Hyeok-Il Kwon, Min-Suk Song, Se Mi Kim, Young-Il Kim, Young-Jae Si, In-Won Lee, Hiep Dinh Nguyen, Ok Sarah Shin, Chul-Joong Kim, Young Ki Choi
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 from the H5N1 virus resulted in significantly enhanced pathogenicity compared with the parental H5N8 virus in mice...
September 5, 2017: Virulence
https://www.readbyqxmd.com/read/28860997/specific-features-of-the-hypothalamic-leptin-signaling-response-to-cold-exposure-are-reflected-in-peripheral-blood-mononuclear-cells-in-rats-and-ferrets
#12
Bàrbara Reynés, Marlou Klein Hazebroek, Estefanía García-Ruiz, Jaap Keijer, Paula Oliver, Andreu Palou
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 evaluated the potential of peripheral blood mononuclear cells to reflect hypothalamic molecular responses...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28854363/folding-of-the-cerebral-cortex-requires-cdk5-in-upper-layer-neurons-in-gyrencephalic-mammals
#13
Yohei Shinmyo, Yukari Terashita, Tung Anh Dinh Duong, Toshihide Horiike, Muneo Kawasumi, Kazuyoshi Hosomichi, Atsushi Tajima, Hiroshi Kawasaki
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 gyrencephalic brains of ferrets...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28846898/pathogenicity-testing-of-influenza-candidate-vaccine-viruses-in-the-ferret-model
#14
Jessica A Belser, Adam Johnson, Joanna A Pulit-Penaloza, Claudia Pappas, Melissa B Pearce, Wen-Pin Tzeng, M Jaber Hossain, Callie Ridenour, Li Wang, Li-Mei Chen, David E Wentworth, Jacqueline M Katz, Taronna R Maines, Terrence M Tumpey
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 that cause zoonotic infections requires ongoing monitoring and surveillance, and, when a lack of antigenic match between circulating viruses and available CVVs is identified, the production of new CVVs...
August 25, 2017: Virology
https://www.readbyqxmd.com/read/28844407/novel-hemagglutinin-nanoparticle-influenza-vaccine-with-matrix-m%C3%A2-adjuvant-induces-hemagglutination-inhibition-neutralizing-and-protective-responses-in-ferrets-against-homologous-and-drifted-a-h3n2-subtypes
#15
Gale Smith, Ye Liu, David Flyer, Michael J Massare, Bin Zhou, Nita Patel, Larry Ellingsworth, Maggie Lewis, James F Cummings, Greg Glenn
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) and microneutralizing (MN) antibodies against a broad range of influenza A(H3N2) subtypes...
September 25, 2017: Vaccine
https://www.readbyqxmd.com/read/28821753/dynamic-reconfiguration-of-cortical-functional-connectivity-across-brain-states
#16
Iain Stitt, Karl J Hollensteiner, Edgar Galindo-Leon, Florian Pieper, Eva Fiedler, Thomas Stieglitz, Gerhard Engler, Guido Nolte, Andreas K Engel
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 ferret using chronically implanted micro-electrocorticographic (µECoG) arrays positioned over occipital, parietal, and temporal cortical regions...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820381/possible-role-of-fish-as-transport-hosts-for-dracunculus-spp-larvae
#17
Christopher A Cleveland, Mark L Eberhard, Alec T Thompson, Stephen J Smith, Hubert Zirimwabagabo, Robert Bringolf, Michael J Yabsley
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.
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28820366/determination-of-ferret-enteric-coronavirus-genome-in-laboratory-ferrets
#18
Tian-Cheng Li, Sayaka Yoshizaki, Michiyo Kataoka, Yen Hai Doan, Yasushi Ami, Yuriko Suzaki, Tomofumi Nakamura, Naokazu Takeda, Takaji Wakita
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.
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28819261/modified-vaccinia-virus-ankara-preferentially-targets-antigen-presenting-cells-in-vitro-ex-vivo-and-in-vivo
#19
Arwen F Altenburg, Carolien E van de Sandt, Bobby W S Li, Ronan J MacLoughlin, Ron A M Fouchier, Geert van Amerongen, Asisa Volz, Rudi W Hendriks, Rik L de Swart, Gerd Sutter, Guus F Rimmelzwaan, Rory D de Vries
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 infected antigen presenting cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814512/zoonotic-risk-pathogenesis-and-transmission-of-avian-origin-h3n2-canine-influenza-virus
#20
Hailiang Sun, Sherry Blackmon, Guohua Yang, Kaitlyn Waters, Tao Li, Ratanaporn Tangwangvivat, Yifei Xu, Daniel Shyu, Feng Wen, Jim Cooley, Lucy Senter, Xiaoxu Lin, Richard Jarman, Larry Hanson, Richard Webby, Xiu-Feng Wan
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 antigenically distinct from contemporary human H3N2 IAVs, suggesting there may be minimal herd immunity in humans...
August 16, 2017: Journal of Virology
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