188 research outputs found

    Antibiotic resistance of enterobacteria isolated from freshwater bodies of different climatic zones

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    An important problem of our time is the resistance of bacteria to antimicrobial drugs. Surface water bodies accumulate all kinds of antibiotic-resistant bacteria found in the catchment area.The aim. To compare the antibiotic resistance of enterobacteria isolated from freshwater ecosystems of the Murmansk and Ryazan regions.Methods. Isolation was performed by the disk-diffusion method. For species identification, the “Rapid-entero 200 M” test system was used. Sensitivity was determined to 19 antibacterial drugs by the disk diffusion method in accordance with the requirements of MUK 4.2.1980-04 and Clinical guidelines (2014). Data interpretation was carried out using EUCAST v. 7.0 (2017) criteria and the WHONET software package.Results. In 2016, 771 isolates of enterobacteria were isolated from the water bodies of the Ryazan region, 323 isolates from the Murmansk region. The results showed that enterobacteria were found in all surveyed surface water bodies. Citrobacter (36 %), Escherichia coli (21 %) and Providencia (21 %) dominated in the Ryazan region, while Citrobacter (35 %) and Enterobacter (21 %) dominated in the Murmansk region. Enterobacteria resistant to one or more antimicrobials dominate in both regions. The phenotype of multiple drug resistance (MDR) was found in 82.62 % of isolates in Ryazan and 95.98 % in Murmansk regions. The extreme resistance phenotype (XDR) was more common among enterobacteria isolated from water bodies of the Ryazan region. In both districts, there was a fairly high level of resistance to beta-lactam antibiotics. In both regions, the quinolones were the most effective group for inhibiting the growth of enterobacteria.Conclusion. The results of the study show that the spread of antibiotic-resistant isolates of enterobacteria in freshwater ecosystems occurs everywhere, but in northern waters this process is slower

    Analysis of natural variants of the hepatitis C virus internal ribosome entry site reveals that primary sequence plays a key role in cap-independent translation

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    The HCV internal ribosome entry site (IRES) spans a region of ∼340 nt that encompasses most of the 5′ untranslated region (5′UTR) of the viral mRNA and the first 24–40 nt of the core-coding region. To investigate the implication of altering the primary sequence of the 5′UTR on IRES activity, naturally occurring variants of the 5′UTR were isolated from clinical samples and analyzed. The impact of the identified mutations on translation was evaluated in the context of RLuc/FLuc bicistronic RNAs. Results show that depending on their location within the RNA structure, these naturally occurring mutations cause a range of effects on IRES activity. However, mutations within subdomain IIId hinder HCV IRES-mediated translation. In an attempt to explain these data, the dynamic behavior of the subdomain IIId was analyzed by means of molecular dynamics (MD) simulations. Despite the loss of function, MD simulations predicted that mutant G266A/G268U possesses a structure similar to the wt-RNA. This prediction was validated by analyzing the secondary structure of the isolated IIId RNAs by circular dichroism spectroscopy in the presence or absence of Mg2+ ions. These data strongly suggest that the primary sequence of subdomain IIId plays a key role in HCV IRES-mediated translation

    An internal ribosome entry site in the 5′ untranslated region of epidermal growth factor receptor allows hypoxic expression

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    The expression of epidermal growth factor receptor (EGFR/ERBB1/HER1) is implicated in the progress of numerous cancers, a feature that has been exploited in the development of EGFR antibodies and EGFR tyrosine kinase inhibitors as anti-cancer drugs. However, EGFR also has important normal cellular functions, leading to serious side effects when EGFR is inhibited. One damaging characteristic of many oncogenes is the ability to be expressed in the hypoxic conditions associated with the tumour interior. It has previously been demonstrated that expression of EGFR is maintained in hypoxic conditions via an unknown mechanism of translational control, despite global translation rates generally being attenuated under hypoxic conditions. In this report, we demonstrate that the human EGFR 5′ untranslated region (UTR) sequence can initiate the expression of a downstream open reading frame via an internal ribosome entry site (IRES). We show that this effect is not due to either cryptic promoter activity or splicing events. We have investigated the requirement of the EGFR IRES for eukaryotic initiation factor 4A (eIF4A), which is an RNA helicase responsible for processing RNA secondary structure as part of translation initiation. Treatment with hippuristanol (a potent inhibitor of eIF4A) caused a decrease in EGFR 5′ UTR-driven reporter activity and also a reduction in EGFR protein level. Importantly, we show that expression of a reporter gene under the control of the EGFR IRES is maintained under hypoxic conditions despite a fall in global translation rates

    The 3′-Terminal Hexamer Sequence of Classical swine fever virus RNA Plays a Role in Negatively Regulating the IRES-Mediated Translation

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    The 3′ untranslated region (UTR) is usually involved in the switch of the translation and replication for a positive-sense RNA virus. To understand the 3′ UTR involved in an internal ribosome entry site (IRES)-mediated translation in Classical swine fever virus (CSFV), we first confirmed the predicted secondary structure (designated as SLI, SLII, SLIII, and SLIV) by enzymatic probing. Using a reporter assay in which the luciferase expression is under the control of CSFV 5′ and 3′ UTRs, we found that the 3′ UTR harbors the positive and negative regulatory elements for translational control. Unlike other stem loops, SLI acts as a repressor for expression of the reporter gene. The negative cis-acting element in SLI is further mapped to the very 3′-end hexamer CGGCCC sequence. Further, the CSFV IRES-mediated translation can be enhanced by the heterologous 3′-ends such as the poly(A) or the 3′ UTR of Hepatitis C virus (HCV). Interestingly, such an enhancement was repressed by flanking this hexamer to the end of poly(A) or HCV 3′ UTR. After sequence comparison and alignment, we have found that this hexamer sequence could hypothetically base pair with the sequence in the IRES IIId1, the 40 S ribosomal subunit binding site for the translational initiation, located at the 5′ UTR. In conclusion, we have found that the 3′-end terminal sequence can play a role in regulating the translation of CSFV

    Search for slow magnetic monopoles with the NOvA detector on the surface

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    We report a search for a magnetic monopole component of the cosmic-ray flux in a 95-day exposure of the NOvA experiment’s Far Detector, a 14 kt segmented liquid scintillator detector designed primarily to observe GeV-scale electron neutrinos. No events consistent with monopoles were observed, setting an upper limit on the flux of 2 × 10−14 cm−2 s−1 sr−1 at 90% C.L. for monopole speed 6 × 10−4 < β < 5 × 10−3 and mass greater than 5 × 108 GeV. Because of NOvA’s small overburden of 3 meters-water equivalent, this constraint covers a previously unexplored low-mass region

    Measurement of the νe -Nucleus Charged-Current Double-Differential Cross Section at «eν »=2.4 GeV Using NOvA

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    The inclusive electron neutrino charged-current cross section is measured in the NOvA near detector using 8.02×1020 protons-on-target in the NuMI beam. The sample of GeV electron neutrino interactions is the largest analyzed to date and is limited by ≃17% systematic rather than the ≃7.4% statistical uncertainties. The double-differential cross section in final-state electron energy and angle is presented for the first time, together with the single-differential dependence on Q2 (squared four-momentum transfer) and energy, in the range 1 GeV≤Eν<6 GeV. Detailed comparisons are made to the predictions of the GENIE, GiBUU, NEUT, and NuWro neutrino event generators. The data do not strongly favor a model over the others consistently across all three cross sections measured, though some models have especially good or poor agreement in the single differential cross section vs Q2

    Measurement of the double-differential muon-neutrino charged-current inclusive cross section in the NOvA near detector

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    We report cross-section measurements of the final-state muon kinematics for νμ charged-current interactions in the NOvA near detector using an accumulated 8.09×1020 protons on target in the NuMI beam. We present the results as a double-differential cross section in the observed outgoing muon energy and angle, as well as single-differential cross sections in the derived neutrino energy, Eν, and square of the four-momentum transfer, Q2. We compare the results to inclusive cross-section predictions from various neutrino event generators via χ2 calculations using a covariance matrix that accounts for bin-to-bin correlations of systematic uncertainties. These comparisons show a clear discrepancy between the data and each of the tested predictions at forward muon angle and low Q2, indicating a missing suppression of the cross section in current neutrino-nucleus scattering models
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