428 research outputs found

    Armenia and Belarus: caught between the EU's and Russia's conditionalities?

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    This article looks into Armenia's and Belarus’ engagement with the European Union's (EU) and Russia's conditionalities, the two EU Eastern Partnership (EaP) countries that are also members of the Russia-led Eurasian Economic Union (EAEU). While paying attention to political, economic (including energy and technical) as well as security dimensions of the EU's and Russia's approaches, as proposed in the present special section, the article demonstrates that the conditionalities extended by the EU and Russia to the two countries in question have differed. In their turn, Armenia and Belarus have reacted differently to Russia's and the EU's conditionalities. Against the backdrop of the changing significance ascribed to both the EU's and Russia's policies towards their common neighbourhood since the 1990s, the present contribution identifies and analyses factors that account for the diverging positions of Armenia and Belarus, including the type of regime, the geopolitical considerations, the stakes in the economic and energy spheres and the predisposition to integration. The article shows that in the resulting complex context, Armenia and Belarus have been able to influence the shape and content of the EU's and Russia's conditionalities, although in a different way and to a different extent.Ministry of Education and Science (UID/CPO/ 00758/2013

    Effects of a wheat bran extract containing arabinoxylan oligosaccharides on gastrointestinal health parameters in healthy adult human volunteers : a double-blind, randomised, placebo-controlled, cross-over trial

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    Wheat bran extract (WBE) is a food-grade soluble fibre preparation that is highly enriched in arabinoxylan oligosaccharides. In this placebo-controlled cross-over human intervention trial, tolerance and effects on colonic protein and carbohydrate fermentation were studied. After a 1-week run-in period, sixty-three healthy adult volunteers consumed 3, 10 and 0 g WBE/d for 3 weeks in a random order, with 2 weeks' washout between each treatment period. Fasting blood samples were collected at the end of the run-in period and at the end of each treatment period for analysis of haematological and clinical chemistry parameters. Additionally, subjects collected a stool sample for analysis of microbiota, SCFA and pH. A urine sample, collected over 48 h, was used for analysis of p-cresol and phenol content. Finally, the subjects completed questionnaires scoring occurrence frequency and distress severity of eighteen gastrointestinal symptoms. Urinary p-cresol excretion was significantly decreased after WBE consumption at 10 g/d. Faecal bifidobacteria levels were significantly increased after daily intake of 10 g WBE. Additionally, WBE intake at 10 g/d increased faecal SCFA concentrations and lowered faecal pH, indicating increased colonic fermentation of WBE into desired metabolites. At 10 g/d, WBE caused a mild increase in flatulence occurrence frequency and distress severity and a tendency for a mild decrease in constipation occurrence frequency. In conclusion, WBE is well tolerated at doses up to 10 g/d in healthy adults volunteers. Intake of 10 g WBE/d exerts beneficial effects on gut health parameters

    The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

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    Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

    The European Union, Russia and the Eastern region: The analytics of government for sustainable cohabitation

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    This article applies the Foucauldian premise of governmentality and the analytics of government framework to demonstrate how exclusive modalities of power – of the European Union (EU) and Russia – and their competing rationalities relate, intersect and become, counter-intuitively, inextricable in their exercise of governance over the eastern neighbourhood. This particular approach focuses on power as a process to gauge the prospects for compatibility and cohabitation between the EU and Russia. Using original primary evidence, this article contends that cohabitation between these two exclusive power modalities is possible and even inevitable, if they were to legitimise their influence over the contested eastern region. It also exposes a fundamental flaw in the existing power systems, as demonstrated so vividly in the case of Ukraine – that is, a neglect for the essential value of freedom in fostering subjection to one’s authority, and the role of ‘the other’ in shaping the EU–Russian power relations in the contested regio

    The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption

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    Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification

    Acetate Kinase Isozymes Confer Robustness in Acetate Metabolism

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    Acetate kinase (ACK) (EC no: 2.7.2.1) interconverts acetyl-phosphate and acetate to either catabolize or synthesize acetyl-CoA dependent on the metabolic requirement. Among all ACK entries available in UniProt, we found that around 45% are multiple ACKs in some organisms including more than 300 species but surprisingly, little work has been done to clarify whether this has any significance. In an attempt to gain further insight we have studied the two ACKs (AckA1, AckA2) encoded by two neighboring genes conserved in Lactococcus lactis (L. lactis) by analyzing protein sequences, characterizing transcription structure, determining enzyme characteristics and effect on growth physiology. The results show that the two ACKs are most likely individually transcribed. AckA1 has a much higher turnover number and AckA2 has a much higher affinity for acetate in vitro. Consistently, growth experiments of mutant strains reveal that AckA1 has a higher capacity for acetate production which allows faster growth in an environment with high acetate concentration. Meanwhile, AckA2 is important for fast acetate-dependent growth at low concentration of acetate. The results demonstrate that the two ACKs have complementary physiological roles in L. lactis to maintain a robust acetate metabolism for fast growth at different extracellular acetate concentrations. The existence of ACK isozymes may reflect a common evolutionary strategy in bacteria in an environment with varying concentrations of acetate

    QTL mapping of improving forage maize starch degradability in European elite maize germplasm

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    Improving maize starch content is of great importance for both forage and grain yield. In this study, 13 starch degradability traits were analyzed including percentage of the seedling area, floury endosperm, hard endosperm of total grain area, percentage of the floury endosperm surface, and vitreousness ratio surface hard: floury endosperm surface, etc. We mapped quantitative trait loci (QTL) in a biparental population of 309 doubled haploid lines (DHL) based on field phenotyping at two locations. A genetic linkage map was constructed using 168 SSR (simple sequence repeat) markers, which covered 1508 cM of the maize genome, with an average distance of 9.0 cM. Close phenotypic and genotypic correlations were found for all traits, and were all statistically significant (P = 0.01) at two locations. Major QTL for more than two traits were detected, especially in two regions in bins 4.05-4.06 and 7.04-7.05, associated with 13 and 9 traits, respectively. This study contributes to marker assisted breeding and also to fine mapping candidate genes associated with maize starch degradability

    Enterobactin-Mediated Delivery of ÎČ-Lactam Antibiotics Enhances Antibacterial Activity against Pathogenic Escherichia coli

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    The design, synthesis, and characterization of enterobactin–antibiotic conjugates, hereafter Ent-Amp/Amx, where the ÎČ-lactam antibiotics ampicillin (Amp) and amoxicillin (Amx) are linked to a monofunctionalized enterobactin scaffold via a stable poly(ethylene glycol) linker are reported. Under conditions of iron limitation, these siderophore-modified antibiotics provide enhanced antibacterial activity against Escherichia coli strains, including uropathogenic E. coli CFT073 and UTI89, enterohemorrhagic E. coli O157:H7, and enterotoxigenic E. coli O78:H11, compared to the parent ÎČ-lactams. Studies with E. coli K-12 derivatives defective in ferric enterobactin transport reveal that the enhanced antibacterial activity observed for this strain requires the outer membrane ferric enterobactin transporter FepA. A remarkable 1000-fold decrease in minimum inhibitory concentration (MIC) value is observed for uropathogenic E. coli CFT073 relative to Amp/Amx, and time-kill kinetic studies demonstrate that Ent-Amp/Amx kill this strain more rapidly at 10-fold lower concentrations than the parent antibiotics. Moreover, Ent-Amp and Ent-Amx selectively kill E. coli CFT073 co-cultured with other bacterial species such as Staphylococcus aureus, and Ent-Amp exhibits low cytotoxicity against human T84 intestinal cells in both the apo and iron-bound forms. These studies demonstrate that the native enterobactin platform provides a means to effectively deliver antibacterial cargo across the outer membrane permeability barrier of Gram-negative pathogens utilizing enterobactin for iron acquisition.Pacific Southwest Regional Center of Excellence for Biodefense and Emerging Infectious DiseaseKinship Foundation. Searle Scholars ProgramMassachusetts Institute of Technology. Department of Chemistr
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