The Crystal Structure of the Escherichia coli Autoinducer-2 Processing Protein LsrF

Many bacteria produce and respond to the quorum sensing signal autoinducer-2 (AI-2). Escherichia coli and Salmonella typhimurium are among the species with the lsr operon, an operon containing AI-2 transport and processing genes that are up regulated in response to AI-2. One of the Lsr proteins, LsrF, has been implicated in processing the phosphorylated form of AI-2. Here, we present the structure of LsrF, unliganded and in complex with two phospho-AI-2 analogues, ribose-5-phosphate and ribulose-5-phosphate. The crystal structure shows that LsrF is a decamer of (αβ)8-barrels that exhibit a previously unseen N-terminal domain swap and have high structural homology with aldolases that process phosphorylated sugars. Ligand binding sites and key catalytic residues are structurally conserved, strongly implicating LsrF as a class I aldolase

Higher spin interactions with scalar matter on constant curvature spacetimes: conserved current and cubic coupling generating functions

Cubic couplings between a complex scalar field and a tower of symmetric tensor gauge fields of all ranks are investigated on any constant curvature spacetime of dimension d>2. Following Noether's method, the gauge fields interact with the scalar field via minimal coupling to the conserved currents. A symmetric conserved current, bilinear in the scalar field and containing up to r derivatives, is obtained for any rank r from its flat spacetime counterpart in dimension d+1, via a radial dimensional reduction valid precisely for the mass-square domain of unitarity in (anti) de Sitter spacetime of dimension d. The infinite collection of conserved currents and cubic vertices are summarized in a compact form by making use of generating functions and of the Weyl/Wigner quantization on constant curvature spaces.Comment: 35+1 pages, v2: two references added, typos corrected, enlarged discussions in Subsection 5.2 and in Conclusion, to appear in JHE

Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.Funding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184info:eu-repo/semantics/publishedVersio

Effective action in a higher-spin background

We consider a free massless scalar field coupled to an infinite tower of background higher-spin gauge fields via minimal coupling to the traceless conserved currents. The set of Abelian gauge transformations is deformed to the non-Abelian group of unitary operators acting on the scalar field. The gauge invariant effective action is computed perturbatively in the external fields. The structure of the various (divergent or finite) terms is determined. In particular, the quadratic part of the logarithmically divergent (or of the finite) term is expressed in terms of curvatures and related to conformal higher-spin gravity. The generalized higher-spin Weyl anomalies are also determined. The relation with the theory of interacting higher-spin gauge fields on anti de Sitter spacetime via the holographic correspondence is discussed.Comment: 40 pages, Some errors and typos corrected, Version published in JHE

LsrR-Mediated Quorum Sensing Controls Invasiveness of Salmonella typhimurium by Regulating SPI-1 and Flagella Genes

Bacterial cell-to-cell communication, termed quorum sensing (QS), controls bacterial behavior by using various signal molecules. Despite the fact that the LuxS/autoinducer-2 (AI-2) QS system is necessary for normal expression of Salmonella pathogenicity island-1 (SPI-1), the mechanism remains unknown. Here, we report that the LsrR protein, a transcriptional regulator known to be involved in LuxS/AI-2-mediated QS, is also associated with the regulation of SPI-1-mediated Salmonella virulence. We determined that LsrR negatively controls SPI-1 and flagella gene expressions. As phosphorylated AI-2 binds to and inactivates LsrR, LsrR remains active and decreases expression of SPI-1 and flagella genes in the luxS mutant. The reduced expression of those genes resulted in impaired invasion of Salmonella into epithelial cells. Expression of SPI-1 and flagella genes was also reduced by overexpression of the LsrR regulator from a plasmid, but was relieved by exogenous AI-2, which binds to and inactivates LsrR. These results imply that LsrR plays an important role in selecting infectious niche of Salmonella in QS dependent mode

Variables involved in the perception of psychological harassment in the nursing work environment

This is a descriptive-exploratory study with a quantitative approach, with the objective of identifying how nurses perceive psychological harassment at work, the behaviors experienced and the variables involved. In collecting data, two questionnaires were used: one socio-professional and another for identifying the behaviors involving psychological harassment experienced by the subjects in the previous twelve months, along with the duration and frequency of the behaviors. At the end of the questionnaire, a dichotomous question was added, which addressed nurses' perceptions in relation to feeling victimized by psychological harassment at work. Both the questionnaires were applied in electronic and print format between May and September 2010. The data was analyzed through descriptive statistics. The results showed that some of the subjects felt that they were victims of psychological harassment. Only the variables related to characterization of the psychological harassment presented significant association. The following were highlighted among the most-referred-to behaviors: "They question your decisions" and "You receive verbal attacks criticizing work you have done". It's important to open spaces for discussing violence at work, so that managers may establish strategic measures for preventing and containing this type of violence, so as to ensure health, dignity and well-being at work. It is also important to discuss this issue in the academic space, so as to give the theme greater visibility, such that future nurses will be able to identify and appropriately confront this type of violence.Estudio descriptivo-exploratorio de abordaje cuantitativo, con el objetivo de identificar la percepción de enfermeros sobre el asedio moral en el trabajo, las conductas vividas y las variables relacionadas. En la recogida de datos se utilizó un cuestionario socio-profesiográfico y otro para identificar las conductas de asedio moral vividas por los sujetos en los últimos doce meses, el periodo y la frecuencia de las conductas. Al final del cuestionario fue adicionada una cuestión dicotómica relacionada a la percepción del enfermero cuanto a sentirse víctima de asedio moral en el trabajo. Los dos cuestionarios fueran aplicados electrónicamente e impresos entre mayo y septiembre de 2010. Los datos fueran tratados por estadística descriptiva. Los resultados mostraron que los sujetos se sintieron víctimas de asedio moral. Solamente las variables relacionadas a la caracterización del asedio moral presentaron asociación significativa. Entre las conductas más referidas, se destacaron: "Cuestionan las decisiones que usted toma" y "Usted recibe ataques verbales criticando trabajos realizados". Es importante la apertura de espacios de discusión sobre la violencia en el trabajo para que gestores puedan establecer medidas estratégicas de prevención y contención de este tipo de violencia a fin de garantizar la salud, la dignidad y el bienestar del profesional en el trabajo. También es importante discutir el tema en el ámbito académico, con el fin de dar mayor visibilidad a la cuestión, para que los futuras enfermeros puedan identificar y abordar adecuadamente este tipo de violencia.Trata-se de estudo descritivo-exploratório, de abordagem quantitativa, com o objetivo de identificar a percepção de enfermeiros sobre o assédio moral no trabalho, condutas vivenciadas e variáveis envolvidas. Na coleta de dados, utilizaram-se dois questionários: um socioprofissiográfico e outro para identificar as condutas de assédio moral, vivenciadas pelos sujeitos nos últimos 12 meses, o período e a frequência das condutas. Ao final do questionário, foi adicionada uma questão dicotômica que abordava a percepção do enfermeiro em relação a se sentir vítima de assédio moral no trabalho. Ambos os questionários foram aplicados no formato eletrônico e impresso, entre maio e setembro de 2010. Os dados foram tratados por estatística descritiva. Os resultados mostraram que parte dos sujeitos sentiu-se vítima de assédio moral. Somente as variáveis relacionadas à caracterização do assédio moral apresentaram associação significativa. Entre as condutas mais referidas, destacaram-se: "questionam as decisões que você toma" e "você recebe ataques verbais criticando trabalhos realizados". É importante a abertura de espaços para discussão sobre a violência no trabalho, para que gestores possam estabelecer medidas estratégicas de prevenção e contenção desse tipo de violência, a fim de garantir a saúde, a dignidade e o bem-estar no trabalho. Torna-se importante, também, discutir o assunto no espaço acadêmico, a fim de dar maior visibilidade ao tema, para que futuros enfermeiros possam identificar e enfrentar adequadamente esse tipo de violência

Opposing effects of final population density and stress on Escherichia coli mutation rate

Evolution depends on mutations. For an individual genotype, the rate at which mutations arise is known to increase with various stressors (stress-induced mutagenesis-SIM) and decrease at high final population density (density-associated mutation-rate plasticity-DAMP). We hypothesised that these two forms of mutation-rate plasticity would have opposing effects across a nutrient gradient. Here we test this hypothesis, culturing Escherichia coli in increasingly rich media. We distinguish an increase in mutation rate with added nutrients through SIM (dependent on error-prone polymerases Pol IV and Pol V) and an opposing effect of DAMP (dependent on MutT, which removes oxidised G nucleotides). The combination of DAMP and SIM results in a mutation rate minimum at intermediate nutrient levels (which can support 7 × 10  cells ml ). These findings demonstrate a strikingly close and nuanced relationship of ecological factors-stress and population density-with mutation, the fuel of all evolution

Patterning Bacterial Communities on Epithelial Cells

Micropatterning of bacteria using aqueous two phase system (ATPS) enables the localized culture and formation of physically separated bacterial communities on human epithelial cell sheets. This method was used to compare the effects of Escherichia coli strain MG1655 and an isogenic invasive counterpart that expresses the invasin (inv) gene from Yersinia pseudotuberculosis on the underlying epithelial cell layer. Large portions of the cell layer beneath the invasive strain were killed or detached while the non-invasive E. coli had no apparent effect on the epithelial cell layer over a 24 h observation period. In addition, simultaneous testing of the localized effects of three different bacterial species; E. coli MG1655, Shigella boydii KACC 10792 and Pseudomonas sp DSM 50906 on an epithelial cell layer is also demonstrated. The paper further shows the ability to use a bacterial predator, Bdellovibrio bacteriovorus HD 100, to selectively remove the E. coli, S. boydii and P. sp communities from this bacteria-patterned epithelial cell layer. Importantly, predation and removal of the P. Sp was critical for maintaining viability of the underlying epithelial cells. Although this paper focuses on a few specific cell types, the technique should be broadly applicable to understand a variety of bacteria-epithelial cell interactionsopen3