Mutation Analysis in Regulator DNA-Binding Regions for Antimicrobial Efflux Pumps in 17,000 Pseudomonas aeruginosa Genomes

Mutations leading to upregulation of efflux pumps can produce multiple drug resistance in the pathogen Pseudomonas aeruginosa. Changes in their DNA binding regions, i.e., palindromic operators, can compromise pump depression and subsequently enhance resistance against several antibacterials and biocides. Here, we have identified (pseudo)palindromic repeats close to promoters of genes encoding 13 core drug-efflux pumps of P. aeruginosa. This framework was applied to detect mutations in these repeats in 17,292 genomes. Eighty-nine percent of isolates carried at least one mutation. Eight binary genetic properties potentially related to expression were calculated for mutations. These included palindromicity reduction, mutation type, positioning within the repeat and DNA-bending shift. High-risk ST298, ST308 and ST357 clones commonly carried four conserved mutations while ST175 and the cystic fibrosis-linked ST649 clones showed none. Remarkably, a T-to-C transition in the fourth position of the upstream repeat for mexEF-oprN was nearly exclusive of the high-risk ST111 clone. Other mutations were associated with high-risk sublineages using sample geotemporal metadata. Moreover, 1.5% of isolates carried five or more mutations suggesting they undergo an alternative program for regulation of their effluxome. Overall, P. aeruginosa shows a wide range of operator mutations with a potential effect on efflux pump expression and antibiotic resistance.This research was funded by Acción Estratégica en Salud from the ISCIII, grant MPY 509/19. This research was also supported by Personalized and Precision Medicine grant from the Instituto de Salud Carlos III (MePRAM Project, PMP22/00092), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU.S

Prediction factors of permanent maxillary canine impaction

Objective: The main objective of this study was to evaluate whether impaction of the maxillary permanent canine (IMPC) can be predicted by factors such as sex, class of malocclusion, facial biotype, microdontia/peg-shaped maxillary permanent lateral incisor or congenital missing maxillary permanent lateral incisor. Methods: The initial study sample consisted of 95 children with 9 years old, which were selected from the clinic of the Faculty of Dental Medicine, University of Porto in the period between 2008 and 2010. In April 2014, all participants were asked to return for clinical examination. Agreed to participate in the study 51 children, now with the chronological age of 13-14 years. In the intraoral exam at 2014, the eruption of 13 and 23 was checked. Statistical analyses were performed with the IBM SPSS Statistics 22.0 statistical package. The statistical methods for the associations between each variable and IMPC included chi-square tests.P values less than 0.05 were considered significant. Results: There was no statistically significant differences (p < 0.05) between the studied predictive factors and the eruption of the maxillary permanent canine. Further investigations with large samples should be performed in order to increase our knowledge in this field. Conclusion: No statistically significant differences were found between the predictive variables analyzed and the impaction of the maxillary permanent canine.(undefined)info:eu-repo/semantics/publishedVersio

Two Antimycin A Analogues from Marine-Derived Actinomycete Streptomyces lusitanus

Two new antimycin A analogues, antimycin B1 and B2 (1–2), were isolated from a spent broth of a marine-derived bacterium, Streptomyces lusitanus. The structures of 1 and 2 were established on the basis of spectroscopic analyses and chemical methods. The isolated compounds were tested for their anti-bacterial potency. Compound 1 was found to be inactive against the bacteria Bacillus subtilis, Staphyloccocus aureus, and Loktanella hongkongensis. Compound 2 showed antibacterial activities against S. aureus and L. hongkongensis with MIC values of 32.0 and 8.0 μg/mL, respectively

Whole-brain imaging of freely-moving zebrafish

One of the holy grails of neuroscience is to record the activity of every neuron in the brain while an animal moves freely and performs complex behavioral tasks. While important steps forward have been taken recently in large-scale neural recording in rodent models, single neuron resolution across the entire mammalian brain remains elusive. In contrast the larval zebrafish offers great promise in this regard. Zebrafish are a vertebrate model with substantial homology to the mammalian brain, but their transparency allows whole-brain recordings of genetically-encoded fluorescent indicators at single-neuron resolution using optical microscopy techniques. Furthermore zebrafish begin to show a complex repertoire of natural behavior from an early age, including hunting small, fast-moving prey using visual cues. Until recently work to address the neural bases of these behaviors mostly relied on assays where the fish was immobilized under the microscope objective, and stimuli such as prey were presented virtually. However significant progress has recently been made in developing brain imaging techniques for zebrafish which are not immobilized. Here we discuss recent advances, focusing particularly on techniques based on light-field microscopy. We also draw attention to several important outstanding issues which remain to be addressed to increase the ecological validity of the results obtained

Age and geochemistry of the Charlestown Group, Ireland:Implications for the Grampian orogeny, its mineral potential and the Ordovician timescale

Accurately reconstructing the growth of continental margins during episodes of ocean closure has important implications for understanding the formation, preservation and location of mineral deposits in ancient orogens. The Charlestown Group of county Mayo, Ireland, forms an important yet understudied link in the Caledonian-Appalachian orogenic belt located between the well documented sectors of western Ireland and Northern Ireland. We have reassessed its role in the Ordovician Grampian orogeny, based on new fieldwork, high-resolution airborne geophysics, graptolite biostratigraphy, U–Pb zircon dating, whole rock geochemistry, and an examination of historic drillcore from across the volcanic inlier. The Charlestown Group can be divided into three formations: Horan, Carracastle, and Tawnyinah. The Horan Formation comprises a mixed sequence of tholeiitic to calc-alkaline basalt, crystal tuff and sedimentary rocks (e.g. black shale, chert), forming within an evolving peri-Laurentian affinity island arc. The presence of graptolites Pseudisograptus of the manubriatus group and the discovery of Exigraptus uniformis and Skiagraptus gnomonicus favour a latest Dapingian (i.e. Yapeenian Ya 2/late Arenig) age for the Horan Formation (equivalent to c. 471.2–470.5 Ma according to the timescale of Sadler et al., 2009). Together with three new U–Pb zircon ages of 471.95–470.82 Ma from enclosing felsic tuffs and volcanic breccias, this fauna provides an important new constraint for calibrating the Middle Ordovician timescale. Overlying deposits of the Carracastle and Tawnyinah formations are dominated by LILE- and LREE-enriched calc-alkaline andesitic tuffs and flows, coarse volcanic breccias and quartz-feldspar porphyritic intrusive rocks, overlain by more silicic tuffs and volcanic breccias with rare occurrences of sedimentary rocks. The relatively young age for the Charlestown Group in the Grampian orogeny, coupled with high Th/Yb and zircon inheritance (c. 2.7 Ga) in intrusive rocks indicate that the arc was founded upon continental crust (either composite Laurentian margin or microcontinental block). Regional correlation is best fitted to an association with the post-subduction flip volcanic/intrusive rocks of the Irish Caledonides, specifically the late-stage development of the Tyrone Igneous Complex, intrusive rocks of Connemara (western Ireland) and the Slishwood Division (Co. Sligo). Examination of breccia textures and mineralization across the volcanic inlier questions the previous porphyry hypothesis for the genesis of the Charlestown Cu deposit, which are more consistent with a volcanogenic massive sulfide (VMS) deposit.</p

'This is what democracy looks like' : New Labour's blind spot and peripheral vision

New Labour in government since 1997 has been roundly criticized for not possessing a clear, coherent and consistent democratic vision. The absence of such a grand vision has resulted, from this critical perspective, in an absence of 'joined-up' thinking about democracy in an evolving multi-level state. Tensions have been all too apparent between the government's desire to exert central direction - manifested in its most pathological form as 'control freakery' - and its democratising initiatives derived from 'third-way' obsessions with 'decentralising', 'empowering' and 'enabling'. The purpose of this article is to examine why New Labour displayed such apparently impaired democratic vision and why it appeared incapable of conceiving of democratic reform 'in the round'. This article seeks to explain these apparent paradoxes, however, through utilising the notion of 'macular degeneration'. In this analysis, the perceived democratic blind spot of New Labour at Westminster is connected to a democratic peripheral vision, which has envisaged innovative participatory and decentred initiatives in governance beyond Westminster