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  • Article
    Manivannan A, Mazumder S, Al-Kourainy N.
    Cureus. 2020 Oct 30;12(10):e11269.
    Type 1 autoimmune hepatitis (AIH) is a rare inflammatory disorder of the liver that may arise at any age, from infancy to adulthood. Long-standing autoimmune hepatitis may progress to cirrhosis and subsequent hepatocellular carcinoma (HCC). However, the true incidence of HCC in AIH patients is unknown as there is a paucity of published data. Currently, there are no established guidelines on screening patients with AIH for HCC. Without screening protocols, patients with AIH may present with late-stage HCC that may have been detected and treated earlier in the disease course. We describe a case of a patient with type 1 AIH who developed stage IIIB HCC in the absence of appropriate screening protocols with complex social determinants leading to barriers to access regular follow-up care.
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  • Article
    Todorova T, Delley B.
    Inorg Chem. 2008 Dec 01;47(23):11269-77.
    The structural parameters, electronic properties, and infrared frequencies of three binuclear ruthenium complexes, [(NH(3))(5)Ru(pyrazine)Ru(NH(3))(5)](n+), n = 4-6, have been investigated with density functional theory. Structural analysis demonstrates that the structure of the mixed-valence 5+, or [II,III], is not an intermediate of the reduced 4+, or [II,II], and the oxidized 6+, or [III,III], compounds. Electronic structure comparison shows that the Ru d(yz) antibonding orbital is empty when n = 5 and 6 and occupied, when n = 4. The infrared frequencies have been calculated for a sequence of models with increasingly detailed accounts of counterions, ranging from the free Creutz-Taube 5+ ion, over jellium embedded, COnductor-like Screening MOdel (COSMO), to the experimental structure of the triclinic [II,III](tos)(5).4H(2)O (tos = p-toluenesulfonate) crystal. Analysis of the Ru vibrations shows that the spectra for the two symmetry-inequivalent Ru atoms are essentially the same. We find that Ru-Ru modes exist near three well-defined frequencies in the solid: at 145, 285, and 345 cm(-1). Similar results are also obtained for the simplified jellium and COSMO models. The spectral properties of these vibrational correlations testify to the existence of two coupled Ru atoms in the same charge state.
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  • Article
    Otchere ID, Coscollá M, Sánchez-Busó L, Asante-Poku A, Brites D, Loiseau C, Meehan C, ... Show More Osei-Wusu S, Forson A, Laryea C, Yahayah AI, Baddoo A, Ansa GA, Aboagye SY, Asare P, Borrell S, Gehre F, Beckert P, Kohl TA, N'dira S, Beisel C, Antonio M, Niemann S, de Jong BC, Parkhill J, Harris SR, Gagneux S, Yeboah-Manu D.
    Sci Rep. 2018 07 26;8(1):11269.
    Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some countries of West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including N = 175 Lineage 5 (L5) and N = 78 Lineage 6 (L6). We found that the genomic diversity of L6 was higher than in L5 despite the smaller sample size. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Even though over 90% of the human T cell epitopes were conserved in both lineages, L6 showed a higher ratio of non-synonymous to synonymous single nucleotide variation in these epitopes overall compared to L5. Of the 10% human T cell epitopes that were variable, most carried mutations that were lineage-specific. Our findings indicate that Maf L5 and L6 differ in some of their population genomic characteristics, possibly reflecting different selection pressures linked to distinct ecological niches.
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  • Article
    Parussulo AL, Bonacin JA, Toma SH, Araki K, Toma HE.
    Langmuir. 2009 Oct 06;25(19):11269-71.
    The presence of anatase and rutile domains on nanocrystalline films of P25 TiO2, as well as the distinct coordination modes of carboxylates on those phases, were revealed by confocal Raman microscopy, a technique that showed to be suitable for imaging the chemical morphology down to submicrometric size.
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  • Article
    Guo Z, Hong H, Sun H, Zhang X, Wu CX, Li B, Cao Y, Chen H.
    Nanoscale. 2021 Jul 07;13(25):11262-11269.
    Single molecule force spectroscopy has emerged as a powerful tool to study protein folding dynamics, ligand-receptor interactions, and various mechanobiological processes. High force precision does not necessarily lead to high force accuracy, as the uncertainties in calibration can bring serious systematic errors. In the case of magnetic tweezers, accurate determination of the applied forces for short biomolecular tethers, by measuring thermal fluctuations of inhomogeneous magnetic beads, remains difficult. Here we address this challenge by showing that the SpyTag/SpyCatcher complex is not only a convenient and genetically encodable covalent linker but also an ideal molecular fingerprint and force marker in single molecule force spectroscopy experiments. By stretching the N-termini of both SpyCatcher and SpyTag, the complex unfolds locally up to the isopeptide bond position in an unzipping geometry, resulting in equilibrium transitions at ∼30 pN with step sizes of ∼3.4 nm. This mechanical feature can be used as the fingerprint to identify single-molecular events. Moreover, the transitions occur with a fast exchange rate and in a narrow force range. Therefore, the real applied forces can be determined accurately based on the force-dependent transitions. The equilibrium forces are insensitive to buffer conditions and temperature, making the calibration applicable to many complicated experimental systems. We provide an example to calibrate protein unfolding forces using this force marker and expect that this method can greatly simplify force calibration in single-molecule force spectroscopy experiments and improve the force accuracy.
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  • Article
    Cartailler J, Schuss Z, Holcman D.
    Sci Rep. 2017 09 12;7(1):11269.
    Voltage and charge distributions in cellular microdomains regulate communications, excitability, and signal transduction. We report here new electrical laws in a biological cell, which follow from a nonlinear electro-diffusion model. These newly discovered laws derive from the geometrical cell-membrane properties, such as membrane curvature, volume, and surface area. The electro-diffusion laws can now be used to predict and interpret voltage distribution in cellular microdomains such as synapses, dendritic spine, cilia and more.
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  • Article
    Yao W, Huang CM, Zhao JX, Huang R, Li WH, Fan PL, Zhou QH.
    Ecol Evol. 2024 Apr;14(4):e11269.
    Limestone forests are an unusual habitat for primates, especially fragmented limestone habitats. However, while some research has been conducted on François' langurs (Trachypithecus francois) in these habitats, there is still a need to improve the understanding of their behavioral adaptations to the fragmented limestone habitat. We collected data on the diet of François' langurs in a fragmented limestone habitat in Encheng National Nature Reserve, southwestern Guangxi, China using instantaneous scanning sampling, and their feeding adaptations to the fragmented forest were examined. The results indicated that a total of 101 species of plants were consumed by the langurs. They also fed on two non-plant components, including cliff minerals and at least one species of insect. The langurs ate a higher number of food species in Encheng when compared with the other geographic populations, and they maintained a high level of food diversity and ate more vines. Moreover, they were highly selective in their use of vegetation in their home range, and fewer plants provided a high-quality food source. During the season when food resources were scarce, the consumption of fruits and young leaves decreased as their availability decreased. This led to the use of other food components, such as mature leaves and seeds. The findings support that François' langurs adjust their feeding behavior to cope with seasonal and micro-variations in their dietary requirements and to adapt to their particular environment.
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  • Article
    Li S, Zheng S.
    Cancer Manag Res. 2020;12:11257-11269.
    BACKGROUND: 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is an effective chemotherapy for colorectal cancer (CRC) in clinic. It remains unclear regarding the effect of circular RNA (circRNA) circ_0032833 on regulating chemosensitivity in CRC.
    METHODS: Drug resistance analysis was performed by Cell Counting Kit-8 (CCK-8) assay. All RNA and protein levels were, respectively, measured via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Cellular colony capacity, apoptosis and metastasis were evaluated using colony formation assay, Annexin-FITC/PI flow cytometry and transwell migration/invasion assays. The molecular combination was notarized using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The in vivo experiment was conducted via xenograft tumors in mice.
    RESULTS: Circ_0032833 was significantly up-regulated in FOLFOX-resistant CRC and associated with drug resistance. Knockdown of circ_0032833 could sensitize FOLFOX-resistant CRC cells to 5-fluorouracil and oxaliplatin. Circ_0032833 was a miR-125-5p sponge, and miR-125-5p overexpression was responsible for the effect of circ_0032833 knockdown on 5-fluorouracil and oxaliplatin sensitivities. Besides, miR-125-5p targeted Musashi1 (MSI1) to increase the susceptibility of 5-fluorouracil and oxaliplatin in FOLFOX-resistant CRC cells. We found that circ_0032833 generated the regulation on MSI1 by sponging miR-125-5p. Circ_0032833 down-regulation also promoted the 5-fluorouracil and oxaliplatin sensitivities partly through the miR-125-5p/MSI1 axis in vivo.
    CONCLUSION: This study illuminated an unambiguous mechanism circ_0032833/miR-125-5p/MSI1 on regulating 5-fluorouracil and oxaliplatin sensitivities in FOLFOX therapy, maybe providing a deep insight of resistance formation and developing a novel strategy to enhance chemosensitivity in CRC.
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  • Article
    Chen Z, Xie Y, Huang W, Qin C, Yu A, Lai G.
    Nanoscale. 2019 Jun 21;11(23):11262-11269.
    As an important biomarker for early disease diagnosis, microRNA-21 (miRNA-21) has attracted considerable attention owing to its accurate detection. Herein we combine the one-step biorecognition reaction at a vertically aligned nanostructure-based biosensor with the T7 exonuclease (Exo)-assisted target recycling to develop a novel electrochemical bioassay method for miRNA-21 detection. The vertically aligned nanointerface is constructed through the covalent attachment of terminally carboxylated single-walled carbon nanotubes (SWCNTs) at an aryldiazonium salt-modified electrode, which enables the noncovalent adsorption of a ferrocene-labeled single-stranded signal DNA to obtain the biosensor. Upon its incubation with a target miRNA-21 solution, DNA/RNA hybridized duplexes will form and release from the electrode surface, leading to the corresponding electrochemical signal decrease of the biosensor. Moreover, this biorecognition reaction can also trigger the T7 Exo-assisted target recycling to achieve great signal amplification. Together with the highly efficient biorecognition and excellent electron transfer promotion at the vertically aligned SWCNTs, this biosensor exhibits a wide linear range varying from 0.01 to 100 pM and a low detection limit down to 3.5 fM. Considering its obvious performance superiority and convenient manipulations, this vertically aligned SWCNT-based electrochemical biosensing method has extensive potential for practical applications.
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  • Article
    Xu Z, Zhang Y, Xu M, Zheng X, Lin M, Pan J, Ye C, Deng Y, Jiang C, Lin Y, Lu X, Chi P.
    Onco Targets Ther. 2019;12:11255-11269.
    PURPOSE: This study aimed to evaluate the role of colony-stimulating factor 2 (CSF2) in chemotherapy resistance, prognosis, and immune response and to identify its possible mechanisms underlying drug resistance.
    METHODS: Drug-resistant cell lines were obtained by successively increasing drug concentration. RNA-Seq was performed to screen hub genes. CSF2 expression was analyzed via immunohistochemistry. Moreover, The Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER) dataset, and R2 platform were used to explore the correlations among CSF2 expression, prognosis, and immune response.
    RESULTS: RNA-Seq indicated that microRNAs in cancer, P53 signaling pathway, and cell cycle were associated with FOLFOX chemotherapy resistance. Protein-protein interaction (PPI), molecular complex detection (MOCDE), and qRT-PCR analysis verified CSF2 as the hub gene in chemotherapy resistance. Moreover, CSF2 expression was lower in the normal tissue than in the cancerous tissue (P<0.05). Higher expression of CSF2 was associated with poor OS and DFS in colon cancer patients (P<0.05). We further found similar results in the Oncomine database and R2 platform (P<0.05). A higher expression of CSF2 in the CRC tissue may be caused by demethylation, which was verified using the TCGA datasets. Moreover, GSEA demonstrated that CSF2 was associated with immune response, which was consistent with results reported using TIMER datasets.
    CONCLUSION: CSF2 is a novel biomarker and a prognostic factor for the survival of CRC patients affecting the immune response, and an overexpression of CSF2 in CRC patients may be caused by DNA demethylation.
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  • Article
    Roy C, Drover D, Simmonds A.
    Can J Urol. 2022 08;29(4):11266-11269.
    We present the case of a 73-year-old male patient who presented with obstructive urinary symptoms, pelvic pressure, and hematuria. CT imaging revealed a heterogenous prostate enlargement, and MRI demonstrated the mass to be arising from the seminal vesicle. Prostate biopsies showed benign tissue. Surgical excision was completed and pathology revealed it to be an epithelioid smooth muscle neoplasm of uncertain biologic potential. This is only the second known case of such a seminal vesicle tumour. As soft tissue sarcomas of the seminal vesicle emerge in the literature, we may develop a better understanding of their biologic behaviour and prognostic potential.
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  • Article
    Zhong C, Xin M, He L, Sun G, Shen F.
    Medicine (Baltimore). 2018 Jul;97(27):e11269.
    BACKGROUND: Studies on the prognostic role of von Willebrand factor (vWF) in patients with atrial fibrillation (AF) are conflicting. This meta-analysis aimed to evaluate the association of elevated circulating vWF level with adverse outcomes in patients with AF.
    METHODS: PubMed and Embase were used to search literature through August 2017. Prospective observational studies that evaluated the association of elevated vWF level with major adverse cardiac events (MACEs) and all-cause mortality in patients with AF were deemed eligible. The MACEs included death, stroke/transient ischemic attack, heart failure, myocardial infarction, and systemic/peripheral embolism.
    RESULTS: A total of 6 studies were included this meta-analysis. Patients with AF with the highest vWF level were independently associated with greater risk of MACEs (risk ratio [RR] 2.20; 95% confidence intervals [CI] 1.61-3.01) and all-cause mortality (RR 1.63; 95% CI 1.39-1.91). Subgroup analysis showed that the prognostic role of higher vWF level was consistently observed in each defined subgroups.
    CONCLUSION: Patients with AF with elevated vWF level are independently associated with a higher risk of MACEs and all-cause mortality. However, more well-designed prospective studies are needed to confirm these findings.
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  • Article
    Goiriena-Goikoetxea M, Guslienko KY, Rouco M, Orue I, Berganza E, Jaafar M, Asenjo A, Fernández-Gubieda ML, Fernández Barquín L, García-Arribas A.
    Nanoscale. 2017 Aug 10;9(31):11269-11278.
    We present a detailed study of the magnetic behavior of Permalloy (Ni80Fe20 alloy) circular nanodots with small radii (30 nm and 70 nm) and different thicknesses (30 nm or 50 nm). Despite the small size of the dots, the measured hysteresis loops manifestly display the features of classical vortex behavior with zero remanence and lobes at high magnetic fields. This is remarkable because the size of the magnetic vortex core is comparable to the dot diameter, as revealed by magnetic force microscopy and micromagnetic simulations. The dot ground states are close to the border of the vortex stability and, depending on the dot size, the magnetization distribution combines attributes of the typical vortex, single domain states or even presents features resembling magnetic skyrmions. An analytical model of the dot magnetization reversal, accounting for the large vortex core size, is developed to explain the observed behavior, providing a rather good agreement with the experimental results. The study extends the understanding of magnetic nanodots beyond the classical vortex concept (where the vortex core spins have a negligible influence on the magnetic behavior) and can therefore be useful for improving emerging spintronic applications, such as spin-torque nano-oscillators. It also delimits the feasibility of producing a well-defined vortex configuration in sub-100 nm dots, enabling the intracellular magneto-mechanical actuation for biomedical applications.
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  • Article
    Wu G, Li GB, Dai B.
    Molecules. 2012 Sep 21;17(9):11269-80.
    KIF6 is a class of molecular motor from the kinesin superfamily. Recently, multiple large studies consisting mainly of Europeans have shown that KIF6 Trp719Arg SNP may be a new predictive factor for coronary artery disease (CAD) event risk. The allelic frequency distribution of rs20455 is different in various populations, yet studies among the Han population, one of the largest ethnic groups in the World, have not been conducted. This study is aimed to evaluate the association of KIF6 Trp719Arg variant with angiographic CAD and serum lipid levels in the Han population from northern China. In this case-controlled study, peripheral blood samples were collected from 356 patients and 568 controls of Han Chinese origin. Genotyping was performed by a high-resolution melting curve. The impact of rs20455 on CAD and non-fatal MI was evaluated in a dominant genetic model with stepwise multiple regression analysis. There were no significant differences of genotypes and allele frequency between angiographic CAD and control groups (p > 0.05); however, that of MI and non-MI subgroups were significant differences (p < 0.05). After adjusting for significant risk factors, angiographic CAD risk was not significantly increased in 719Arg allele carriers compared with non-carriers. Further analysis revealed that the non-fatal MI risk and triglyceride levels were significantly higher in 719Arg allele carriers than non-carriers. In conclusion, KIF6 719Arg allele was not an independent risk factor for angiographic CAD susceptibility in Han populations from northern China. However, it was associated with a significantly higher TG level, which may indicate an increased myocardial infarction risk in angiographic CAD patients.
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  • Article
    Nazar H, Nazar Z, Simpson J, Yeung A, Whittlesea C.
    BMJ Open. 2016 08 26;6(8):e011269.
    OBJECTIVES: To demonstrate the contribution of community pharmacy from NHS 111 referrals out of hours (OOH) for emergency supply repeat medication requests via presentation of service activity, community pharmacist feedback and lean thinking transformation.
    DESIGN: Descriptive service evaluation using routine service activity data over the pilot period; survey of community pharmacists, and service redesign through lean thinking transformation.
    SETTING: North East of England NHS 111 provider and accredited community pharmacies across the North East of England.
    PARTICIPANTS: Patients calling the North East of England NHS 111 provider during OOH with emergency repeat medication supply requests.
    INTERVENTIONS: NHS 111 referral to community pharmacies for assessment and if appropriate, supply of emergency repeat medication.
    MAIN OUTCOME MEASURES: Number of emergency repeat medication supply referrals, completion rates, reasons for rejections, time of request, reason for access, medication(s), pharmaceutical advice and services provided. Secondary outcomes were community pharmacist feedback and lean thinking transformation of the patient pathway.
    RESULTS: NHS 111 referred 1468 patients to 114 community pharmacies (15/12/2014-7/4/2015). Most patients presented on Saturdays, with increased activity over national holidays. Community pharmacists completed 951 (64.8%) referrals providing 2297 medications; 412 were high risk. The most common reason for rejecting referrals was no medication in stock. Community pharmacists were positive about the provision of this service. The lean thinking transformation reduced the number of non-added value steps, waits and bottlenecks in the patient pathway.
    CONCLUSIONS: NHS 111 can redirect callers OOH from urgent and emergency care services to community pharmacy for management of emergency repeat medication supply. Existing IT and community pharmacy regulations allowed patients to receive a medication supply and pharmaceutical advice. Community pharmacists supported integration into the NHS OOH services. Adopting lean thinking provided a structured framework to evaluate and redesign the service with the aim to improve effectiveness and efficiency.
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  • Article
    Jain P, Hung HC, Lin X, Ma J, Zhang P, Sun F, Wu K, Jiang S.
    Langmuir. 2017 10 24;33(42):11264-11269.
    The development of nonfouling zwitterionic materials has a wide range of biomedical and engineering applications. This work delineates the design and synthesis of a new zwitterionic material based on a naturally occurring compatible solute, ectoine, which is known to possess additional protective properties that stabilize even whole cells against ultraviolet radiation or cytotoxins. These properties and applications of ectoine inspire us to design a functional monomer containing the natural zwitterion moiety of ectoine imparting nonfouling properties and the methacrylate moiety for polymerization. The synthesis route designed for the ectoine methacrylate monomer is simple with a high yield, which is characterized by nuclear magnetic resonance spectroscopy and mass spectrometry. After monomer synthesis, we have prepared a poly(ectoine) hydrogel via thermal polymerization. The equilibrium water content, degree of cross-linking, mechanical strength, and nonfouling properties are determined for polyectoine hydrogels with different cross-linking conditions. Poly(ectoine) hydrogels are shown to have highly hydrated and excellent nonfouling properties and can be considered to be a promising biomaterial.
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  • Article
    Farsalinos KE, Spyrou A, Stefopoulos C, Tsimopoulou K, Kourkoveli P, Tsiapras D, Kyrzopoulos S, Poulas K, Voudris V.
    Sci Rep. 2015 Jun 17;5:11269.
    Electronic cigarettes (ECs) are nicotine delivery devices that are proposed as tobacco harm reduction products to smokers. Nicotine delivery from ECs is potentially important in their efficacy as smoking substitutes. Herein, nicotine delivery from using a new-generation EC device (variable-wattage, set at 9 W) was evaluated, comparing experienced (vapers) with naïve users (smokers). Twenty-four vapers and 23 smokers participated to the study. They were asked to obtain 10 puffs in 5 minutes and then use the EC ad lib for 60 more minutes (total duration of use: 65 minutes). An 18 mg/mL nicotine-containing liquid was used. Blood samples were obtained at baseline, 5-minutes and every 15 minutes thereafter, while number of puffs and average puff duration were recorded. Although at baseline both groups had similar plasma nicotine levels, smokers consistently exhibited lower levels at all time-periods; at 5-minutes the levels were lower by 46%, while during the subsequent period they were lower by 43% (at 65-minutes) to 54% (at 20-minutes). Both groups took similar number of puffs, but smokers had average puff duration of 2.3 s compared to 3.5 s in vapers. Even in vapers, plasma nicotine levels at 5 minutes were lower than those observed after smoking 1 tobacco cigarette.
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  • Article
    Guo T, Feng Y, Liu Q, Yang X, Jiang T, Chen Y, Zhang Q.
    Tumour Biol. 2014 Nov;35(11):11269-75.
    Glioblastoma (GBM) is the most aggressive and malignant glioma. Currently, a few modern surgical and medical therapeutic strategies are applied for GBM, but the prognosis of GBM patients remains poor, and the average median survival time is only 14.6 months. In this study, we for the first time found that the levels of miR-320a were decreased in both GBM patients and glioma cells. In GBM patients, elevated miR-320a expression was associated with better prognosis. In addition, insulin-like growth factor-1 receptor (IGF-1R) was identified as a key direct target of miR-320a. Overexpression of miR-320a led to the inhibition of cell proliferation, migration, invasion, as well as tumorigenesis by targeting IGF-1R, and thus regulated the signaling pathways downstream, including PI3K/AKT and MAPK/ERK. In tumor orthotopic xenograft experiment, the tumor growth was depressed and survival time of mice model was prolonged when miR-320a was overexpressed. Therefore, our results suggested that miR-320a could suppress tumor development and growth by targeting IGF-1R, and miR-320a might serve as a new effective target for anti-cancer therapy strategies.
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  • Article
    Sturm-Ramirez KM, Hulse-Post DJ, Govorkova EA, Humberd J, Seiler P, Puthavathana P, Buranathai C, Nguyen TD, Chaisingh A, Long HT, Naipospos TS, Chen H, Ellis TM, Guan Y, Peiris JS, Webster RG.
    J Virol. 2005 Sep;79(17):11269-79.
    Wild waterfowl are the natural reservoir of all influenza A viruses, and these viruses are usually nonpathogenic in these birds. However, since late 2002, H5N1 outbreaks in Asia have resulted in mortality among waterfowl in recreational parks, domestic flocks, and wild migratory birds. The evolutionary stasis between influenza virus and its natural host may have been disrupted, prompting us to ask whether waterfowl are resistant to H5N1 influenza virus disease and whether they can still act as a reservoir for these viruses. To better understand the biology of H5N1 viruses in ducks and attempt to answer this question, we inoculated juvenile mallards with 23 different H5N1 influenza viruses isolated in Asia between 2003 and 2004. All virus isolates replicated efficiently in inoculated ducks, and 22 were transmitted to susceptible contacts. Viruses replicated to higher levels in the trachea than in the cloaca of both inoculated and contact birds, suggesting that the digestive tract is not the main site of H5N1 influenza virus replication in ducks and that the fecal-oral route may no longer be the main transmission path. The virus isolates' pathogenicities varied from completely nonpathogenic to highly lethal and were positively correlated with tracheal virus titers. Nevertheless, the eight virus isolates that were nonpathogenic in ducks replicated and transmitted efficiently to naïve contacts, suggesting that highly pathogenic H5N1 viruses causing minimal signs of disease in ducks can propagate silently and efficiently among domestic and wild ducks in Asia and that they represent a serious threat to human and veterinary public health.
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