95 research outputs found

    Much more than meh: the 2022 Northern Ireland Assembly elections

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    The Northern Ireland Assembly election of May 2022 was transformational, despite small shifts in the magnitudes of seats won by the two dominant blocs. John Garry, Brendan O’Leary and James Pow discuss the results

    Biomolecular mechanisms of staphylococcal biofilm formation

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    The multitude of biomolecular and regulatory factors involved in staphylococcal adhesion and biofilm formation owe much to their ability to colonize surfaces, allowing the biofilm form to become the preferential bacterial phenotype. Judging by total number, biomass and variety of environments colonized, bacteria can be categorized as the most successful lifeform on earth. This is due to the ability of bacteria and other microorganisms to respond phenotypically via biomolecular processes to the stresses of their surrounding environment. This review focuses on the specific pathways involved in the adhesion of the Gram-positive bacteria Staphylococcus epidermidis and Staphylococcus aureus with reference to the role of specific cell surface adhesins, the ica operon, accumulation-associated proteins and quorum-sensing systems and their significance in medical device-related infection

    Potential strategies for the eradication of multi-drug resistant Gram-negative bacterial infections

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    Antimicrobial resistance is one of the leading threats to society. The increasing burden of multidrug-resistant Gram-negative infection is particularly concerning as such bacteria are demonstrating resistance to nearly all currently licensed therapies. Various strategies have been hypothesized to treat multidrug-resistant Gram-negative infections including: targeting the Gram-negative outer membrane; neutralization of lipopolysaccharide; inhibition of bacterial efflux pumps and prevention of protein folding. Silver and silver nanoparticles, fusogenic liposomes and nanotubes are potential strategies for extending the activity of licensed, Gram-positive selective, antibiotics to Gram-negatives. This may serve as a strategy to fill the current void in pharmaceutical development in the short term. This review outlines the most promising strategies that could be implemented to solve the threat of multidrug-resistant Gram-negative infections. </jats:p

    Self-assembling Ultrashort NSAID-Peptide Nanosponges: Multifunctional Antimicrobial and Anti-inflammatory Materials

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    This paper outlines the design, synthesis and characterisation of innovative NSAID-peptide gelators which demonstrate antimicrobial and anti-inflammatory properties and have potential use as multifunctional materials for biomedical applications.</p

    Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

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    The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa

    Working Group on Unification Referendums on the Island of Ireland: Interim Report

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    The Belfast/Good Friday Agreement of 1998 provides for the possibility of future referendums on the question of whether Northern Ireland should remain in the United Kingdom or become part of a united Ireland. It sets out some of the principles that such votes would need to follow, but it leaves many aspects of the process unclear or unspecified. How would the Secretary of State for Northern Ireland decide whether to call a referendum? Would a vote also be needed in the Republic of Ireland? Would referendums north and south need to be simultaneous? Would they best take place before or after detailed proposals for the form of a united Ireland had been worked out? Who should be able to vote? What should the question on the ballot paper be? How would the referendum campaigns be conducted? This interim report explores possible answers to these and other questions, and sets out the provisional conclusions of the Working Group on Unification Referendums on the Island of Ireland. The Working Group has no collective view on whether such referendums should take place or what the outcome should be if a vote is called. The Group does not see referendums on this subject as imminent. But they could happen in the future. And thinking through in advance what that would involve is vitally important

    OXA1L mutations cause mitochondrial encephalopathy and a combined oxidative phosphorylation defect

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    OXA1, the mitochondrial member of the YidC/Alb3/Oxa1 membrane protein insertase family, is required for the assembly of oxidative phosphorylation complexes IV and V in yeast. However, depletion of human OXA1 (OXA1L) was previously reported to impair assembly of complexes I and V only. We report a patient presenting with severe encephalopathy, hypotonia and developmental delay who died at 5 years showing complex IV deficiency in skeletal muscle. Whole exome sequencing identified biallelic OXA1L variants (c.500507dup, p.(Ser170Glnfs*18) and c.620G>T, p.(Cys207Phe)) that segregated with disease. Patient muscle and fibroblasts showed decreased OXA1L and subunits of complexes IV and V. Crucially, expression of wild-type human OXA1L in patient fibroblasts rescued the complex IV and V defects. Targeted depletion of OXA1L in human cells or Drosophila melanogaster caused defects in the assembly of complexes I, IV and V, consistent with patient data. Immunoprecipitation of OXA1L revealed the enrichment of mtDNA-encoded subunits of complexes I, IV and V. Our data verify the pathogenicity of these OXA1L variants and demonstrate that OXA1L is required for the assembly of multiple respiratory chain complexes.Peer reviewe
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