48 research outputs found

    Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2

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    Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease—a disease endemic especially in the Asia-Pacific region1. Scavenger receptor class B member 2 (SCARB2) is the major receptor of EV71, as well as several other enteroviruses responsible for hand, foot and mouth disease, and plays a key role in cell entry2. The isolated structures of EV71 and SCARB2 are known3,4,5,6, but how they interact to initiate infection is not. Here, we report the EV71–SCARB2 complex structure determined at 3.4 Å resolution using cryo-electron microscopy. This reveals that SCARB2 binds EV71 on the southern rim of the canyon, rather than across the canyon, as predicted3,7,8. Helices 152–163 (α5) and 183–193 (α7) of SCARB2 and the viral protein 1 (VP1) GH and VP2 EF loops of EV71 dominate the interaction, suggesting an allosteric mechanism by which receptor binding might facilitate the low-pH uncoating of the virus in the endosome/lysosome. Remarkably, many residues within the binding footprint are not conserved across SCARB2-dependent enteroviruses; however, a conserved proline and glycine seem to be key residues. Thus, although the virus maintains antigenic variability even within the receptor-binding footprint, the identification of binding ‘hot spots’ may facilitate the design of receptor mimic therapeutics less likely to quickly generate resistance

    Wege des Viruseintritts: am Beispiel der Erkältungsviren

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    Prevalence of Plasmid-Associated Tetracycline Resistance Genes in Multidrug-Resistant <i>Escherichia coli</i> Strains Isolated from Environmental, Animal and Human Samples in Panama

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    Antimicrobial resistance bacteria are nowadays ubiquitous. Its presence has been reported in almost every type of source, from water for agricultural and recreative use, water distribution pipes, and wastewater, to food, fomites, and clinical samples. Enterobacteriaceae, especially Escherichia coli, are not the exception, showing an increased resistance to several antibiotics, causing a global health and economic burden. Therefore, the monitoring of fecal microbiota is important because it is present in numerous reservoirs where gene transfer between commensal and virulent bacteria can take place, representing a potential source of resistant E. coli. In this work, antibiotic resistance profiles of 150 E. coli isolates from environmental, animal, and human samples, collected in three rural areas in Panama, were analyzed. A total of 116 isolates were resistant to at least one of the nine antibiotics tested. Remarkably, almost 100% of these exhibited resistance to tetracycline. Plasmid-associated tetA and tetB genes were detected in 42.86% of the isolates analyzed, tetA being the most prevalent. These results suggest that tetracycline resistance would be used as a convenient indicator of genetic horizontal transfer within a community

    Prevalence of Plasmid-Associated Tetracycline Resistance Genes in Multidrug-Resistant Escherichia coli Strains Isolated from Environmental, Animal and Human Samples in Panama

    No full text
    Antimicrobial resistance bacteria are nowadays ubiquitous. Its presence has been reported in almost every type of source, from water for agricultural and recreative use, water distribution pipes, and wastewater, to food, fomites, and clinical samples. Enterobacteriaceae, especially Escherichia coli, are not the exception, showing an increased resistance to several antibiotics, causing a global health and economic burden. Therefore, the monitoring of fecal microbiota is important because it is present in numerous reservoirs where gene transfer between commensal and virulent bacteria can take place, representing a potential source of resistant E. coli. In this work, antibiotic resistance profiles of 150 E. coli isolates from environmental, animal, and human samples, collected in three rural areas in Panama, were analyzed. A total of 116 isolates were resistant to at least one of the nine antibiotics tested. Remarkably, almost 100% of these exhibited resistance to tetracycline. Plasmid-associated tetA and tetB genes were detected in 42.86% of the isolates analyzed, tetA being the most prevalent. These results suggest that tetracycline resistance would be used as a convenient indicator of genetic horizontal transfer within a community

    Security policy of Sweden after 2009

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    Krievijas iebrukums Gruzijā 2008. gadā rosināja plašas diskusijas par spēka politikas atgriešanos starptautiskās politikas dienaskārtībā. Tas radīja bažas, ka militāri līdzekļi atkal var tikt izmantoti kā politikas instruments. Saskaņā ar reālisma skolu, līdzsvarošanas politikas īstenošana ir viens no galvenajiem veidiem, kā valstis reaģē uz draudīgu un agresīvu spēcīgāku valstu rīcību. Maģistra darba „Zviedrijas drošības politika pēc 2009. gada” galvenais izpētes mērķis ir noskaidrot, vai pēc 2009. gada ir iespējams konstatēt līdzsvarošanas mehānismu izmantošanu Zviedrijas drošības politikā pret Krieviju. Atslēgvārdi: Zviedrija, drošības politika, spēku līdzsvara teorija, cietā līdzsvarošana, maigā līdzsvarošana, KrievijaRussia’s invasion in Georgia in 2008 caused widespread discussion on whether power politics have returned to be a part of international political agenda once again. It caused concern that military means may be used as political tool again. According to realism, implementation of balancing behavior is one of the main reactions to aggressive activities of threatening and more powerful states. The aim of Master thesis “Security policy of Sweden after 2009” is to determine whether tools of balancing have been used in security policy of Sweden towards Russia after 2009. Key words: Sweden, security policy, balance of power theory, hard balancing, soft balancing, Russia

    Translation Initiation Factors eIF3 and HCR1 Control Translation Termination and Stop Codon Read-Through in Yeast Cells

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    Translation is divided into initiation, elongation, termination and ribosome recycling. Earlier work implicated several eukaryotic initiation factors (eIFs) in ribosomal recycling in vitro. Here, we uncover roles for HCR1 and eIF3 in translation termination in vivo. A substantial proportion of eIF3, HCR1 and eukaryotic release factor 3 (eRF3) but not eIF5 (a well-defined “initiation-specific” binding partner of eIF3) specifically co-sediments with 80S couples isolated from RNase-treated heavy polysomes in an eRF1-dependent manner, indicating the presence of eIF3 and HCR1 on terminating ribosomes. eIF3 and HCR1 also occur in ribosome- and RNA-free complexes with both eRFs and the recycling factor ABCE1/RLI1. Several eIF3 mutations reduce rates of stop codon read-through and genetically interact with mutant eRFs. In contrast, a slow growing deletion of hcr1 increases read-through and accumulates eRF3 in heavy polysomes in a manner suppressible by overexpressed ABCE1/RLI1. Based on these and other findings we propose that upon stop codon recognition, HCR1 promotes eRF3·GDP ejection from the post-termination complexes to allow binding of its interacting partner ABCE1/RLI1. Furthermore, the fact that high dosage of ABCE1/RLI1 fully suppresses the slow growth phenotype of hcr1? as well as its termination but not initiation defects implies that the termination function of HCR1 is more critical for optimal proliferation than its function in translation initiation. Based on these and other observations we suggest that the assignment of HCR1 as a bona fide eIF3 subunit should be reconsidered. Together our work characterizes novel roles of eIF3 and HCR1 in stop codon recognition, defining a communication bridge between the initiation and termination/recycling phases of translation
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