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1.
BMC Infect Dis ; 21(1): 265, 2021 Mar 17.
Article in English | MEDLINE | ID: mdl-33731022

ABSTRACT

BACKGROUND: Increasing arbovirus infections have been a global burden in recent decades. Many countries have experienced the periodic emergence of arbovirus diseases. However, information on the prevalence of arboviruses is largely unknown or infrequently updated because of the lack of surveillance studies, especially in Africa. METHODS: A surveillance study was conducted in Gabon, Central Africa, on arboviruses, which are a major public health concern in Africa, including: West Nile virus (WNV), dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). Serological and molecular assays were performed to investigate past infection history and the current status of infection, using serum samples collected from healthy individuals and febrile patients, respectively. RESULTS: The overall seroprevalence during 2014-2017 was estimated to be 25.3% for WNV, 20.4% for DENV, 40.3% for ZIKV, 60.7% for YFV, 61.2% for CHIKV, and 14.3% for RVFV. No significant differences were found in the seroprevalence of any of the viruses between the male and female populations. However, a focus on the mean age in each arbovirus-seropositive individual showed a significantly younger age in WNV- and DENV-seropositive individuals than in CHIKV-seropositive individuals, indicating that WNV and DENV caused a relatively recent epidemic in the region, whereas CHIKV had actively circulated before. Of note, this indication was supported by the detection of both WNV and DENV genomes in serum samples collected from febrile patients after 2016. CONCLUSIONS: This study revealed the recent re-emergence of WNV and DENV in Gabon as well as the latest seroprevalence state of the major arboviruses, which indicated the different potential risks of virus infections and virus-specific circulation patterns. This information will be helpful for public health organizations and will enable a rapid response towards these arbovirus infections, thereby preventing future spread in the country.


Subject(s)
Arboviruses/isolation & purification , Dengue/epidemiology , Zika Virus Infection/epidemiology , Adolescent , Animals , Arbovirus Infections/diagnosis , Arbovirus Infections/epidemiology , Arboviruses/classification , Child , Child, Preschool , Communicable Diseases, Emerging , Dengue/diagnosis , Female , Fever/epidemiology , Fever/virology , Gabon/epidemiology , Humans , Infant , Male , Public Health , Seroepidemiologic Studies , Zika Virus Infection/diagnosis
2.
Int J Infect Dis ; 105: 452-459, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33667697

ABSTRACT

OBJECTIVES: Lymphocytic choriomeningitis virus (LCMV), a human pathogenic arenavirus, is distributed worldwide. However, no human cases have been reported in Africa. This study aimed to investigate the current situation and potential risks of LCMV infection in Gabon, Central Africa. METHODS: A total of 492 human samples were screened to detect LCMV genome RNA and anti-LCMV IgG antibodies using reverse transcription-quantitative PCR and enzyme-linked immunosorbent assay (ELISA), respectively. ELISA-positive samples were further examined using a neutralization assay. Viral RNAs and antibodies were also analyzed in 326 animal samples, including rodents, shrews, and bushmeat. RESULTS: While no LCMV RNA was detected in human samples, the overall seroprevalence was 21.5% and was significantly higher in male and adult populations. The neutralization assay identified seven samples with neutralizing activity. LCMV RNA was detected in one species of rodent (Lophuromys sikapusi) and a porcupine, and anti-LCMV IgG antibodies were detected in four rodents and three shrews. CONCLUSIONS: This study determined for the first time the seroprevalence of LCMV in Gabon, and revealed that local rodents, shrews, and porcupines in areas surrounding semi-urban cities posed an infection risk. Hence, LCMV infection should be considered a significant public health concern in Africa.

3.
Gan To Kagaku Ryoho ; 48(1): 57-61, 2021 Jan.
Article in Japanese | MEDLINE | ID: mdl-33468724

ABSTRACT

OBJECTIVE: Risk factors for immune-related adverse events(irAEs)associated with immune checkpoint inhibitors(ICIs) remain to be obscure. Therefore, we evaluated the patient background and clinical findings to identify risk factors for the development of irAEs. METHODS: The subjects consisted of 86 patients treated with ICIs between August 2018 and March 2020. They were classified into 2 groups who developed irAEs(irAE group)and did not develop irAEs(non-irAE group). RESULTS: The median age of the subjects was 70 years(39-84 years), and there were 65 males. The underlying disease was non-small cell lung cancer in 51 patients, gastric cancer in 14, renal cell cancer in 9, urothelial cancer in 11, and MSI-high small bowel cancer in 1. The irAE group, in whom treatment with ICIs was discontinued, included 16 patients(18.6%), and the non-irAE group included 70 patients(81.4%). The median number of treatment cycles was 8(1-91), and the median treatment period was 4 months(1-45 months). Evaluation in our hospital revealed no significant background factors, such as gender, age, or the treatment period, as risk factors for the development of eras. Lung disorders were frequently observed after the third-line treatment and in patients with non-small cell lung cancer. CONCLUSION: At present, the prediction of the development of irAEs is difficult. Careful follow-up observation and early irAEs management are important. In addition, further studies are necessary to identify risk factors for the development of irAEs.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Kidney Neoplasms , Lung Neoplasms , Aged , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/drug therapy , Male , Retrospective Studies , Risk Factors
4.
J Am Chem Soc ; 2020 Dec 30.
Article in English | MEDLINE | ID: mdl-33378189

ABSTRACT

Dianionic bis(propionate)-naphthalenediimide (PCNDI2-) formed simple 2:1 cation-anion salts of (M+)2(PCNDI2-)·(H2O)n (M+ = Li+, Na+, K+, Rb+, and Cs+), which exhibited reversible H2O adsorption-desorption behavior because of the presence of their electrostatically binding crystal lattices. The maximum H2O adsorption amounts (n) for M+ = Li+, Na+, K+, Rb+, and Cs+ were 0.25, 6.0, 4.0, 6.0, and 2.0, respectively, whereas the reversible gate-opening (gate-closing) H2O adsorption-desorption isotherms were observed at 273 and 298 K, except for M+ = Li+. High ionic conductivities of around 10-4-10-5 S cm-1 were observed in M+ = Na+ and K+ salts, whereas short-range thermal fluctuations occurred in large cations of M+ = Rb+ and Cs+. The change in the electrostatic lattice energy for M+ = Na+ and K+ salts during the H2O adsorption-desorption cycles was significantly larger than those for M+ = Rb+ and Cs+. Therefore, the Na+ and K+ salts had a considerably flexible electrostatic crystal lattice with a large amplitude of lattice modulation during the H2O sorption cycle. In contrast, the lattice modulation for M+ = Rb+ and Cs+ salts involved a low magnitude of ion displacements, forming a relatively rigid cation-anion electrostatic crystal lattice. The flash-photolysis time-resolved microwave conductivity and transition absorption spectroscopy results revealed the high electron mobility of H2O-adsorbed thin films, wherein the crystallized H2O molecules did not act as electron-trapping sites. The values of electron mobility increased in the order of Cs+ ≈ Rb+ > K+ > Na+ > Li+.

6.
PLoS Negl Trop Dis ; 14(11): e0008855, 2020 11.
Article in English | MEDLINE | ID: mdl-33147214

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic novel coronavirus that has caused a worldwide outbreak. Here we describe a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay that uses a portable device for efficient detection of SARS-CoV-2. This RT-LAMP assay specifically detected SARS-CoV-2 without cross-reacting with the most closely related human coronavirus, SARS-CoV. Clinical evaluation of nasal swab samples from suspected SARS-CoV-2 pneumonia (COVID-19) patients showed that the assay could detect over 23.7 copies within 15 min with a 100% probability. Since the RT-LAMP assay can be performed with a portable battery-supported device, it is a rapid, simple, and sensitive diagnostic assay for COVID-19 that can be available at point-of-care. We also developed the RT-LAMP assay without the RNA extraction step-Direct RT-LAMP, which could detect more than 1.43 x 103 copies within 15 min with a 100% probability in clinical evaluation test. Although the Direct RT-LAMP assay was less sensitive than the standard RT-LAMP, the Direct RT-LAMP assay can be available as the rapid first screening of COVID-19 in poorly equipped areas, such as rural areas in developing countries.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/diagnosis , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Pneumonia, Viral/diagnosis , Humans , Pandemics , Point-of-Care Systems , Time Factors
7.
ACS Appl Mater Interfaces ; 12(33): 37391-37399, 2020 Aug 19.
Article in English | MEDLINE | ID: mdl-32814389

ABSTRACT

Polar H2O molecules generally act as trapping sites and suppress the electron mobility of n-type organic semiconductors, making chemical design of H2O-tolerant and responsive n-type semiconductors an important step toward multifunctional electron-ion coupling devices. The introduction of effective electrostatic interactions between potassium ions (K+) and carboxylate (-COO-) anions into the electron-transporting naphthalenediimide π-framework enables the design of high-performance H2O-tolerant n-type semiconductors with a reversible H2O adsorption-desorption ability, where the electron mobility and K+ ionic conductivity were coupled with the reversible H2O sorption behavior. The reversible H2O adsorption into the crystals enhanced the electron mobility from 0.04 to 0.28 cm2 V-1 s-1, whereas the K+ ionic conductivity decreased from 3.4 × 10-5 to 4.7 × 10-7 S cm-1. Because this reversible electron-ion conducting switch is responsive to H2O sorption behavior, it is a strong candidate for H2O gating carrier transport systems.

8.
J Viral Hepat ; 27(11): 1234-1242, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32564517

ABSTRACT

Although a high seroprevalence of antibodies against hepatitis A virus (HAV) has been estimated in Central Africa, the current status of both HAV infections and seroprevalence of anti-HAV antibodies remains unclear due to a paucity of surveillance data available. We conducted a serological survey during 2015-2017 in Gabon, Central Africa, and confirmed a high seroprevalence of anti-HAV antibodies in all age groups. To identify the currently circulating HAV strains and to reveal the epidemiological and genetic characteristics of the virus, we conducted molecular surveillance in a total of 1007 patients presenting febrile illness. Through HAV detection and sequencing, we identified subgenotype IIA (HAV-IIA) infections in the country throughout the year. A significant prevalence trend emerged in the young child population, presenting several infection peaks which appeared to be unrelated to dry or rainy seasons. Whole-genome sequencing and phylogenetic analyses revealed local HAV-IIA evolutionary events in Central Africa, indicating the circulation of HAV-IIA strains of a region-specific lineage. Recombination analysis of complete genome sequences revealed potential recombination events in Gabonese HAV strains. Interestingly, Gabonese HAV-IIA possibly acquired the 5'-untranslated region (5'-UTR) of the rare subgenotype HAV-IIB in recent years, suggesting the present existence of HAV-IIB in Central Africa. These findings indicate a currently stable HAV-IIA circulation in Gabon, with a high risk of infections in children aged under 5 years. Our findings will enhance the understanding of the current status of HAV infections in Central Africa and provide new insight into the molecular epidemiology and evolution of HAV genotype II.

9.
Int J Infect Dis ; 91: 129-136, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31821892

ABSTRACT

OBJECTIVES: Dengue outbreaks, mainly caused by dengue virus serotype 2 (DENV-2), occurred in 2007 and in 2010 in Gabon, Central Africa. However, information on DENV infections has been insufficient since 2010. The aim of this study was to investigate the current DENV infection scenario and the risk of repeated infections in Gabon. METHODS: During 2015-2017, serum samples were collected from enrolled febrile participants and were tested for DENV infection using RT-qPCR. DENV-positive samples were analyzed for a history of previous DENV infection(s) using ELISA. The complete DENV genome was sequenced to analyze the phylogeny of Gabonese DENV strains. RESULTS: DENV-3 was exclusively detected, with a high rate of anti-DENV IgG seropositivity among DENV-3-positive participants. DENV-3 showed higher infection rates in adults and the infection was seasonal with peaks in the rainy seasons. Phylogenetic analysis revealed that Gabonese DENV-3 originated from West African strains and has been circulating continuously in Gabon since at least 2010, when the first DENV-3 case was reported. CONCLUSIONS: These findings indicate stable DENV-3 circulation and the risk of repeated DENV infections in Gabon, highlighting the need for continuous monitoring to control DENV infections.


Subject(s)
Dengue Virus/isolation & purification , Dengue/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Dengue/virology , Dengue Virus/classification , Dengue Virus/genetics , Female , Gabon/epidemiology , Humans , Infant , Male , Middle Aged , Phylogeny , Real-Time Polymerase Chain Reaction , Seasons , Seroepidemiologic Studies , Serogroup , Young Adult
10.
J Med Virol ; 92(2): 251-256, 2020 02.
Article in English | MEDLINE | ID: mdl-31538666

ABSTRACT

Hepatitis B virus (HBV) infection remains to be a major public health issue worldwide, although there is currently a safe vaccine and effective antiviral treatments. In surveillance of infectious diseases in Gabon, HBV viremia was detected in patients with febrile. Whole-genome sequencing was conducted to characterize the HBV strains currently circulating in Gabon and to investigate HBV genome diversity during viremia. Phylogenetic analysis revealed the existence of former subgenotype A5, which exhibits a particular pattern of distribution from several West and Central African countries to Haiti. Furthermore, sequencing analysis identified two similar HBV strains mixed in one sample, and a very rare 1-base pair insertion in the viral precore region. This insertion caused a frameshift mutation, indicating the production of an aberrant fusion protein of the HBV x and e antigens. Our data showed that the detected HBV strain was possibly in an "evolving" state during viremia, a phase of active replication.

11.
Arch Virol ; 164(2): 457-472, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30415389

ABSTRACT

Surveillance studies of influenza A virus of swine (IAV-S) have accumulated information regarding IAVs-S circulating in Thailand, but how IAVs-S evolve within a farm remains unclear. In the present study, we isolated 82 A(H1N1)pdm09 and 87 H3N2 viruses from four farms from 2011 through 2017. We then phylogenetically and antigenically analyzed the isolates to elucidate their evolution within each farm. Phylogenetic analysis demonstrated multiple introductions of A(H1N1)pdm09 viruses that resembled epidemic A(H1N1)pdm09 strains in humans in Thailand, and they reassorted with H3N2 viruses as well as other A(H1N1)pdm09 viruses. Antigenic analysis revealed that the viruses had acquired antigenic diversity either by accumulating substitutions in the hemagglutinin protein or through the introduction of IAV-S strains with different antigenicity. Our results, obtained through continuous longitudinal surveillance, revealed that IAV-S can be maintained on a pig farm over several years through the generation of antigenic diversity due to the accumulation of mutations, introduction of new strains, and reassortment events.


Subject(s)
Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/immunology , Orthomyxoviridae Infections/veterinary , Swine Diseases/virology , Animals , Antigenic Variation , Genetic Variation , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Influenza A Virus, H1N1 Subtype/classification , Influenza A Virus, H1N1 Subtype/isolation & purification , Influenza A Virus, H3N2 Subtype/classification , Influenza A Virus, H3N2 Subtype/isolation & purification , Longitudinal Studies , Orthomyxoviridae Infections/virology , Phylogeny , Swine , Thailand
12.
PLoS Negl Trop Dis ; 12(11): e0006971, 2018 11.
Article in English | MEDLINE | ID: mdl-30500827

ABSTRACT

Lassa virus (LASV) is endemic in parts of West Africa where it causes Lassa fever (LF), a viral hemorrhagic fever with frequent fatal outcomes. The diverse LASV strains are grouped into six major lineages based on the geographical location of the isolated strains. In this study, we have focused on the lineage II strains from southern Nigeria. We determined the viral sequences from positive cases of LF reported at tertiary hospitals in Ebonyi and Enugu between 2012 and 2016. Reverse transcription-polymerase chain reaction (RT-PCR) showed that 29 out of 123 suspected cases were positive for the virus among which 11 viral gene sequences were determined. Phylogenetic analysis of the complete coding sequences of the four viral proteins revealed that lineage II strains are broadly divided into two genetic clades that diverged from a common ancestor 195 years ago. One clade, consisting of strains from Ebonyi and Enugu, was more conserved than the other from Irrua, although the four viral proteins were evolving at similar rates in both clades. These results suggested that the viruses of these clades have been distinctively evolving in geographically separate parts of southern Nigeria. Furthermore, the epidemiological data of the 2014 outbreak highlighted the role of human-to-human transmission in this outbreak, which was supported by phylogenetic analysis showing that 13 of the 16 sequences clustered together. These results provide new insights into the evolution of LASV in southern Nigeria and have important implications for vaccine development, diagnostic assay design, and LF outbreak management.


Subject(s)
Lassa Fever/virology , Lassa virus/genetics , Lassa virus/isolation & purification , Evolution, Molecular , Genetic Variation , Humans , Lassa Fever/epidemiology , Lassa virus/classification , Nigeria/epidemiology , Phylogeny , Viral Proteins/genetics
13.
Chemistry ; 24(45): 11545-11549, 2018 Aug 09.
Article in English | MEDLINE | ID: mdl-29920806

ABSTRACT

A ruthenium-catalyzed carbocyclization of 2-alkynylstyrenes that involves a very rare 1,2-carbon migration of internal alkynes is reported. Various 1,2-di -and 1,4,7-trisubstituted naphthalenes are synthesized. Mechanistic studies revealed that this reaction proceeds via a disubstituted vinylidene complex as the key intermediate by 1,2-carbon migration of the 2-alkynylstyrenes.

14.
Sci Rep ; 7(1): 13503, 2017 10 18.
Article in English | MEDLINE | ID: mdl-29044149

ABSTRACT

The recent outbreak of Zika virus (ZIKV) disease caused an enormous number of infections in Central and South America, and the unusual increase in the number of infants born with microcephaly associated with ZIKV infection aroused global concern. Here, we developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay using a portable device for the detection of ZIKV. The assay specifically detected ZIKV strains of both Asian and African genotypes without cross-reactivity with other arboviruses, including Dengue and Chikungunya viruses. The assay detected viral RNA at 14.5 TCID50/mL in virus-spiked serum or urine samples within 15 min, although it was slightly less sensitive than reference real time RT-PCR assay. We then evaluated the utility of this assay as a molecular diagnostic test using 90 plasma or serum samples and 99 urine samples collected from 120 suspected cases of arbovirus infection in the states of Paraíba and Pernambuco, Brazil in 2016. The results of this assay were consistent with those of the reference RT-PCR test. This portable RT-LAMP assay was highly specific for ZIKV, and enable rapid diagnosis of the virus infection. Our results provide new insights into ZIKV molecular diagnostics and may improve preparedness for future outbreaks.


Subject(s)
Molecular Diagnostic Techniques/methods , Real-Time Polymerase Chain Reaction/methods , Zika Virus Infection/blood , Animals , Chlorocebus aethiops , Sensitivity and Specificity , Vero Cells , Zika Virus/genetics , Zika Virus Infection/urine
15.
J Anim Ecol ; 86(3): 556-565, 2017 May.
Article in English | MEDLINE | ID: mdl-28146344

ABSTRACT

Insects tend to feed on related hosts. The phylogenetic composition of host plant communities thus plays a prominent role in determining insect specialization, food web structure, and diversity. Previous studies showed a high preference of insect herbivores for congeneric and confamilial hosts suggesting that some levels of host plant relationships may play more prominent role that others. We aim to quantify the effects of host phylogeny on the structure of quantitative plant-herbivore food webs. Further, we identify specific patterns in three insect guilds with different life histories and discuss the role of host plant phylogeny in maintaining their diversity. We studied herbivore assemblages in three temperate forests in Japan and the Czech Republic. Sampling from a canopy crane, a cherry picker and felled trees allowed a complete census of plant-herbivore interactions within three 0·1 ha plots for leaf chewing larvae, miners, and gallers. We analyzed the effects of host phylogeny by comparing the observed food webs with randomized models of host selection. Larval leaf chewers exhibited high generality at all three sites, whereas gallers and miners were almost exclusively monophagous. Leaf chewer generality dropped rapidly when older host lineages (5-80 myr) were collated into a single lineage but only decreased slightly when the most closely related congeneric hosts were collated. This shows that leaf chewer generality has been maintained by feeding on confamilial hosts while only a few herbivores were shared between more distant plant lineages and, surprisingly, between some congeneric hosts. In contrast, miner and galler generality was maintained mainly by the terminal nodes of the host phylogeny and dropped immediately after collating congeneric hosts into single lineages. We show that not all levels of host plant phylogeny are equal in their effect on structuring plant-herbivore food webs. In the case of generalist guilds, it is the phylogeny of deeper plant lineages that drives the food web structure whereas the terminal relationships play minor roles. In contrast, the specialization and abundance of monophagous guilds are affected mainly by the terminal parts of the plant phylogeny and do not generally reflect deeper host phylogeny.


Subject(s)
Food Chain , Forests , Herbivory , Insecta/physiology , Magnoliopsida/classification , Phylogeny , Animals , Czech Republic , Insecta/growth & development , Japan , Larva/physiology , Plant Leaves/physiology
16.
Biochem Biophys Res Commun ; 473(4): 1071-1077, 2016 05 13.
Article in English | MEDLINE | ID: mdl-27059140

ABSTRACT

In the early postnatal period, cerebellar granule cells exhibit an activity-dependent downregulation of a set of immaturation genes involved in cell growth and migration and are shifted to establishment of a mature network formation. Through the use of a granule cell culture and both pharmacological and RNA interference (siRNA) analyses, the present investigation revealed that the downregulation of these immaturation genes is controlled by strikingly unified signaling mechanisms that operate sequentially through the stimulation of AMPA and NMDA receptors, tetrodotoxin-sensitive Na(+) channels and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). This signaling cascade induces the Etv1 transcription factor, and knockdown of Etv1 by a siRNA technique prevented this activity-dependent downregulation of immaturation genes. Thus, taken into consideration the mechanism that controls the upregulation of maturation genes involved in synaptic formation, these results indicate that Etv1 orchestrates the activity-dependent regulation of both maturation and immaturation genes in developing granule cells and plays a key role in specifying the identity of mature granule cells in the cerebellum.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism , Cerebellum/cytology , Cerebellum/physiology , DNA-Binding Proteins/metabolism , Neurons/cytology , Neurons/physiology , Transcription Factors/metabolism , Animals , Cell Differentiation/physiology , Cell Proliferation/physiology , Cells, Cultured , Down-Regulation/physiology , Gene Expression Regulation, Developmental/physiology , Mice , Mice, Inbred ICR , Neurogenesis/physiology
17.
PLoS One ; 11(4): e0153649, 2016.
Article in English | MEDLINE | ID: mdl-27078641

ABSTRACT

Differences in the pathogenicity of genetically closely related H5N1 highly pathogenic avian influenza viruses (HPAIVs) were evaluated in White Leghorn chickens. These viruses varied in the clinical symptoms they induced, including lethality, virus shedding, and replication in host tissues. A comparison of the host responses in the lung, brain, and spleen suggested that the differences in viral replication efficiency were related to the host cytokine response at the early phase of infection, especially variations in the proinflammatory cytokine IL-6. Based on these findings, we inoculated the virus that showed the mildest pathogenicity among the five tested, A/pigeon/Thailand/VSMU-7-NPT/2004, into four breeds of Thai indigenous chicken, Phadu-Hung-Dang (PHD), Chee, Dang, and Luang-Hung-Khao (LHK), to explore effects of genetic background on host response. Among these breeds, Chee, Dang, and LHK showed significantly longer survival times than White Leghorns. Virus shedding from dead Thai indigenous chickens was significantly lower than that from White Leghorns. Although polymorphisms were observed in the Mx and MHC class I genes, there was no significant association between the polymorphisms in these loci and resistance to HPAIV.


Subject(s)
Chickens/virology , Host Specificity , Influenza A Virus, H5N1 Subtype/pathogenicity , Influenza in Birds/virology , Animals , Avian Proteins/genetics , Breeding , Chickens/classification , Chickens/genetics , Cytokines/genetics , Humans , Influenza A Virus, H5N1 Subtype/classification , Influenza in Birds/genetics , Molecular Sequence Data , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Species Specificity , Virulence , Virus Replication , Virus Shedding
18.
Virology ; 484: 203-12, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26115167

ABSTRACT

Following the 2009 H1N1 pandemic, surveillance activities have been accelerated globally to monitor the emergence of novel reassortant viruses. However, the mechanism by which influenza A viruses of swine (IAV-S) acquire novel gene constellations through reassortment events in natural settings remains poorly understood. To explore the mechanism, we collected 785 nasal swabs from pigs in a farm in Thailand from 2011 to 2014. H3N2, H3N1, H1N1 and H1N2 IAVs-S were isolated from a single co-infected sample by plaque purification and showed a high degree of diversity of the genome. In particular, the H1N1 isolates, possessing a novel gene constellation previously unreported in Thailand, exhibited greater variation in internal genes than H3N2 IAVs-S. A pair of isolates, designated H3N2-B and H1N1-D, was determined to have been initially introduced to the farm. These results demonstrate that numerous IAVs-S with various gene constellations can be created in a single co-infected pig via reassortment.


Subject(s)
Coinfection/veterinary , Influenza A virus/growth & development , Influenza A virus/genetics , Orthomyxoviridae Infections/veterinary , Reassortant Viruses/isolation & purification , Recombination, Genetic , Animals , Coinfection/virology , Nasal Mucosa/virology , Orthomyxoviridae Infections/virology , Swine , Thailand
19.
Bioorg Med Chem ; 21(11): 2895-902, 2013 Jun 01.
Article in English | MEDLINE | ID: mdl-23639683

ABSTRACT

The glycopolymer composed of an inulin scaffold and pendent ß-lactosides was developed from commercially available inulin through sequential chemical modification processes composed of tosylation, azidation, and the subsequent Huisgen cyclocoupling with an alkyne-terminated ß-lactoside. The resultant inulin-based glycopolymer has unique dual affinity towards ß-galactoside and α-glucoside specific lectins which is attributable to its pendent ß-lactosides and terminal α-glucoside. Its gellation property was also accessed to find that the inulin-based glycopolymer forms hydrogels whose critical gellation concentration (CGC) was lower than that required for hydrogels made from native inulin. Drug release properties of the inulin-based glycopolymer were also discussed in this paper.


Subject(s)
Drug Carriers/chemical synthesis , Galactosides/chemistry , Hydrogels/chemistry , Inulin/chemical synthesis , Lectins/chemistry , Alkynes/chemistry , Drug Carriers/chemistry , Fluorescein-5-isothiocyanate , Fluorescent Dyes , Inulin/chemistry , Kinetics , Rutin/chemistry , Spectrometry, Fluorescence , Tosyl Compounds/chemistry
20.
Proc Natl Acad Sci U S A ; 109(22): 8734-9, 2012 May 29.
Article in English | MEDLINE | ID: mdl-22586091

ABSTRACT

In maturing postnatal cerebellar granule cells, the Etv1/Er81 transcription factor is induced by sequential activity-dependent mechanisms through stimulation of AMPA and NMDA receptors, voltage-dependent Nav1.2 Na(+) channels, and voltage-dependent Ca(2+) channels. Etv1 then up-regulates a battery of maturation genes involved in the cerebellar circuitry. In this process, BDNF is also induced and participates in the up-regulation of these maturation genes. Using cultures of granule cells, we addressed how the activity-dependent and BDNF signaling mechanisms converge on the regulation of the representative NR2C NMDA receptor and Tiam1 maturation genes. BDNF up-regulated both the NR2C and Tiam1 genes via the TrkB-Erk cascade and this up-regulation was blocked not only by inhibition of the activity-dependent signaling mechanisms but also by suppression of Etv1 expression with Etv1 siRNA. Importantly, Etv1 was selectively phosphorylated by Erk1/2 in the BDNF signaling cascade, and the inhibition of this phosphorylation abrogated the BDNF-induced up-regulation of the NR2C and Tiam1 genes. The luciferase reporter assays in combination with mutations of MEK and Etv1 indicated that the Erk-mediated, phosphorylated Etv1 interacted with the Ets motifs of the NR2C promoter sequence and that phosphorylation at both serine 94 and a cluster of threonines and a serine (Thr139, Thr143, and Ser146) of Etv1 was indispensable for the BDNF-mediated activation of the NR2C promoter activity. This study demonstrates that the NR2C and Tiam1 maturation genes are synergistically controlled by the activity-dependent induction of Etv1 and its phosphorylation by the BDNF signaling cascade.


Subject(s)
Brain-Derived Neurotrophic Factor/pharmacology , Cerebellum/metabolism , DNA-Binding Proteins/genetics , Gene Expression Regulation/drug effects , Transcription Factors/genetics , Animals , Base Sequence , Cell Line, Tumor , Cells, Cultured , Cerebellum/cytology , DNA-Binding Proteins/metabolism , Extracellular Signal-Regulated MAP Kinases/genetics , Extracellular Signal-Regulated MAP Kinases/metabolism , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolism , Immunoblotting , Luciferases/genetics , Luciferases/metabolism , Mice , Mice, Inbred ICR , Mutation , Phosphorylation/drug effects , Promoter Regions, Genetic/genetics , RNA Interference , Receptor, trkB/genetics , Receptor, trkB/metabolism , Receptors, N-Methyl-D-Aspartate/genetics , Receptors, N-Methyl-D-Aspartate/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Serine/genetics , Serine/metabolism , T-Lymphoma Invasion and Metastasis-inducing Protein 1 , Threonine/genetics , Threonine/metabolism , Transcription Factors/metabolism
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