Integrated stress response of Escherichia coli to methylglyoxal : transcriptional readthrough from the nemRA operon enhances protection through increased expression of glyoxalase I

© 2013 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.Peer reviewedPublisher PD

Caracterización genotípica y nuevos tipos de secuencia multilocus de exoU+ de Pseudomonas aeruginosa presente en diferentes infecciones clínicas y entornos

Introducción: The exoU gene, a marker for highly virulent strains of Pseudomonas aeruginosa, is the major contributor to a wide varietyof healthcare-associated infections. Methods: In this study, the antibiotic susceptibility profile, prevalence and genotyping of exoU+ P.aeruginosa were demonstrated. A total of 101 isolates of P. aeruginosa were analysed from different clinical and environmental sources. Results: The antibiotic susceptibility profile classified these isolates as extensively drug resistant (35.6%), multidrug resistant (40.5%) and non-multidrug resistant (23.7%). The prevalence of exoU gene was screened by PCR and 23 exoU+ genotypes were detected which all were clinical isolates. Multilocus sequence typing (MLST) analysis of seven loci assigned these exoU+ genotypes to 21 sequence types (STs) from which 16 new STs were identified. The prevalent STs were ST-308 and ST-235. Phylogenetic analysis using the concatenated nucleotide sequences of the seven housekeeping genes, exoU and the ITS region differentiated these exoU+ strains into five main groups. However, distinct evolutionary origins for some new sequence types were also indicated. Conclusions: The studied isolates showed the coexistence of exoU- and exoU+ genotypes of clinical P. aeruginosa in Kurdistan with a majority of MDR and XDR pattern. The prevalent STs found in other hospitals worldwide and at the international level

Pherotype polymorphism in Streptococcus pneumoniae has no obvious effects on population structure and recombination

Natural transformation in the Gram-positive pathogen Streptococcus pneumoniae occurs when cells become “competent”, a state that is induced in response to high extracellular concentrations of a secreted peptide signal called CSP (Competence Stimulating Peptide) encoded by the comC locus. Two main CSP signal types (pherotypes) are known to dominate the pherotype diversity across strains. Using 4,089 fully sequenced pneumococcal genomes, we confirm that pneumococcal populations are highly genetically structured and that there is significant variation among diverged populations in pherotype frequencies; most carry only a single pherotype. Moreover, we find that the relative frequencies of the two dominant pherotypes significantly vary within a small range across geographical sites. It has been variously proposed that pherotypes either promote genetic exchange among cells expressing the same pherotype, or conversely that they promote recombination between strains bearing different pherotypes. We attempt to distinguish these hypotheses using a bioinformatics approach by estimating recombination frequencies within and between pherotypes across 4,089 full genomes. Despite underlying population structure, we observe extensive recombination between populations; additionally, we found significantly higher (although marginal) rates of genetic exchange between strains expressing different pherotypes than among isolates carrying the same pherotype. Our results indicate that pherotypes do not restrict, and may even slightly facilitate, recombination between strains; however, these marginal effects suggest the more likely possibility that the cause of CSP polymorphism lies outside of its effects on transformation. Our results suggest that the CSP balanced polymorphism does not causally underlie population differentiation. Therefore, when strains carrying different pherotypes encounter one another during co-colonization, genetic exchange can occur without restriction

Knowledge, agency and collective action as barriers to energy-saving behaviour

peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=cloe20Energy saving is becoming a rising priority as a response to climate change and fossil fuel depletion in recent years. However, despite energy-related behaviour change being an important part of many environmental education initiatives, “energy literacy” among citizens remains patchy in both the USA and the UK, with evidence of strong positive attitudes but less consistent knowledge. Whilst it is clear that increasing knowledge does not automatically produce behaviour changes, potential questions must be asked about the logic of focusing solely on behaviour without simultaneously exploring and enhancing understanding of energy issues. This research, undertaken at a higher education institution with a strong focus on sustainability, illustrates the potential risks of targeting behaviour change and individual action at the expense of increasing knowledge, or encouraging collaborative and democratic endeavours. Results from an online survey indicate widespread misconceptions about energy which may reduce the effectiveness of energy-saving behaviours, alongside variable levels of motivation and engagement with energy issues. Respondents report a strong belief in the efficacy of personal changes, yet uncertainty about their capacity to influence business and government alongside a persistent faith in science to provide solutions to energy issues. The paper concludes by reflecting on the challenges arising from these findings for understanding agency and effectiveness in energy relationships

Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced Susceptibility to Death during the 2009 H1N1 Pandemic.

Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 "Spanish flu." Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 "swine flu" pandemic and during the resurgent 2013-2014 H1N1 outbreak for those born at the time of the 1957 H2N2 "Asian flu" pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics.IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918-when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest levels of excess mortality. Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1 pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and 2013-2014 H1N1-dominated season for those born during the heterosubtypic 1957 H2N2 "Asian flu" pandemic. These data highlight the heretofore underappreciated phenomenon that, in certain instances, prior exposure to pandemic influenza virus strains can enhance susceptibility during subsequent pandemics. These results have important implications for pandemic risk assessment and should inform laboratory studies aimed at uncovering the mechanism responsible for this effect

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody–liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: A phase 1 dose-escalation study

BackgroundThis phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.MethodsPatients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.ResultsSixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.ConclusionMM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w