Comparative genomics of prevaccination and modern Bordetella pertussis strains

Contains fulltext : 89571.pdf (publisher's version ) (Open Access)BACKGROUND: Despite vaccination since the 1950s, pertussis has persisted and resurged. It remains a major cause of infant death worldwide and is the most prevalent vaccine-preventable disease in developed countries. The resurgence of pertussis has been associated with the expansion of Bordetella pertussis strains with a novel allele for the pertussis toxin (Ptx) promoter, ptxP3, which have replaced resident ptxP1 strains. Compared to ptxP1 strains, ptxP3 produce more Ptx resulting in increased virulence and immune suppression. To elucidate how B. pertussis has adapted to vaccination, we compared genome sequences of two ptxP3 strains with four strains isolated before and after the introduction vaccination. RESULTS: The distribution of SNPs in regions involved in transcription and translation suggested that changes in gene regulation play an important role in adaptation. No evidence was found for acquisition of novel genes. Modern strains differed significantly from prevaccination strains, both phylogenetically and with respect to particular alleles. The ptxP3 strains were found to have diverged recently from modern ptxP1 strains. Differences between ptxP3 and modern ptxP1 strains included SNPs in a number of pathogenicity-associated genes. Further, both gene inactivation and reactivation was observed in ptxP3 strains relative to modern ptxP1 strains. CONCLUSIONS: Our work suggests that B. pertussis adapted by successive accumulation of SNPs and by gene (in)activation. In particular changes in gene regulation may have played a role in adaptation

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Controlling spins in adsorbed molecules by a chemical switch

The development of chemical systems with switchable molecular spins could lead to the architecture of materials with controllable magnetic or spintronic properties. Here, we present conclusive evidence that the spin of an organometallic molecule coupled to a ferromagnetic substrate can be switched between magnetic off and on states by a chemical stimulus. This is achieved by nitric oxide (NO) functioning as an axial ligand of cobalt(II)tetraphenylporphyrin (CoTPP) ferromagnetically coupled to nickel thin-film (Ni(001)). On NO addition, the coordination sphere of Co2+ is modified and a NO–CoTPP nitrosyl complex is formed, which corresponds to an off state of the Co spin. Thermal dissociation of NO from the nitrosyl complex restores the on state of the Co spin. The NO-induced reversible off–on switching of surface-adsorbed molecular spins observed here is attributed to a spin trans effect

Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model

<p>Abstract</p> <p>Background</p> <p>There is strong evidence demonstrating that activation of epidermal growth factor receptors (EGFRs) leads to tumor growth, progression, invasion and metastasis. Erlotinib and gefitinib, two EGFR-targeted agents, have been shown to be relevant drugs for lung cancer treatment. Recent studies demonstrate that lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2 receptors, is clinically effective against HER-2-overexpressing metastatic breast cancer. In this report, we investigated the activity of lapatinib against non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>We selected the lung cancer cell line A549, which harbors genomic amplification of EGFR and HER-2. Proliferation, cell cycle analysis, clonogenic assays, and signaling cascade analyses (by western blot) were performed <it>in vitro</it>. <it>In vivo </it>experiments with A549 cells xenotransplanted into nude mice treated with lapatinib (with or without radiotherapy) were also carried out.</p> <p>Results</p> <p>Lapatinib dramatically reduced cell proliferation (<it>P </it>< 0.0001), DNA synthesis (<it>P </it>< 0.006), and colony formation capacity (<it>P </it>< 0.0001) in A549 cells <it>in vitro</it>. Furthermore, lapatinib induced G1 cell cycle arrest (<it>P </it>< 0.0001) and apoptotic cell death (<it>P </it>< 0.0006) and reduced cyclin A and B1 levels, which are regulators of S and G2/M cell cycle stages, respectively. Stimulation of apoptosis in lapatinib-treated A549 cells was correlated with increased cleaved PARP, active caspase-3, and proapoptotic Bak-1 levels, and reduction in the antiapoptic IAP-2 and Bcl-xL protein levels. We also demonstrate that lapatinib altered EGFR/HER-2 signaling pathways reducing p-EGFR, p-HER-2, p-ERK1/2, p-AKT, c-Myc and PCNA levels. <it>In vivo </it>experiments revealed that A549 tumor-bearing mice treated with lapatinib had significantly less active tumors (as assessed by PET analysis) (<it>P </it>< 0.04) and smaller in size than controls. In addition, tumors from lapatinib-treated mice showed a dramatic reduction in angiogenesis (<it>P </it>< 0.0001).</p> <p>Conclusion</p> <p>Overall, these data suggest that lapatinib may be a clinically useful agent for the treatment of lung cancer.</p

Planck intermediate results. XLI. A map of lensing-induced B-modes

The secondary cosmic microwave background (CMB) $B$-modes stem from the post-decoupling distortion of the polarization $E$-modes due to the gravitational lensing effect of large-scale structures. These lensing-induced $B$-modes constitute both a valuable probe of the dark matter distribution and an important contaminant for the extraction of the primary CMB $B$-modes from inflation. Planck provides accurate nearly all-sky measurements of both the polarization $E$-modes and the integrated mass distribution via the reconstruction of the CMB lensing potential. By combining these two data products, we have produced an all-sky template map of the lensing-induced $B$-modes using a real-space algorithm that minimizes the impact of sky masks. The cross-correlation of this template with an observed (primordial and secondary) $B$-mode map can be used to measure the lensing $B$-mode power spectrum at multipoles up to $2000$. In particular, when cross-correlating with the $B$-mode contribution directly derived from the Planck polarization maps, we obtain lensing-induced $B$-mode power spectrum measurement at a significance level of $12\,\sigma$, which agrees with the theoretical expectation derived from the Planck best-fit $\Lambda$CDM model. This unique nearly all-sky secondary $B$-mode template, which includes the lensing-induced information from intermediate to small ($10\lesssim \ell\lesssim 1000$) angular scales, is delivered as part of the Planck 2015 public data release. It will be particularly useful for experiments searching for primordial $B$-modes, such as BICEP2/Keck Array or LiteBIRD, since it will enable an estimate to be made of the lensing-induced contribution to the measured total CMB $B$-modes.Comment: 20 pages, 12 figures; Accepted for publication in A&A; The B-mode map is part of the PR2-2015 Cosmology Products; available as Lensing Products in the Planck Legacy Archive http://pla.esac.esa.int/pla/#cosmology; and described in the 'Explanatory Supplement' https://wiki.cosmos.esa.int/planckpla2015/index.php/Specially_processed_maps#2015_Lensing-induced_B-mode_ma

Prácticas del enfermero en el contexto de la atención básica: scoping review

Objective: to identify and categorize the practices performed by nurses working in Primary Health Care and Family Health Strategy Units in light of responsibilities established by the profession’s legal and programmatic frameworks and by the Brazilian Unified Health System. Method: a scoping review was conducted in the following databases: LILACS, IBECS, BDENF, CINAHL and MEDLINE, and the Cochrane and SciELO libraries. Original research papers written by nurses addressing nursing practices in the primary health care context were included. Results: the review comprised 30 studies published between 2005 and 2014. Three categories emerged from the analysis: practices in the service; practices in the community; and management and education practices. Conclusion: the challenges faced by nurses are complex, as care should be centered on the population’s health needs, which requires actions at other levels of clinical and health responsibility. Brazilian nursing has achieved important advancements since the implementation of policies intended to reorganize work. There is, however, a need to shift work processes from being focused on individual procedures to being focused on patients so that an enlarged clinic is the ethical-political imperative guiding the organization of services and professional intervention.Objetivo: identificar e categorizar as práticas exercidas pelos enfermeiros junto às Unidades Básicas e às Equipes de Saúde da Família, à luz das atribuições previstas pelos marcos legais e programáticos da profissão e do Sistema Único de Saúde. Método: realizou-se uma revisão da literatura com o método scoping review, nas bases LILACS, IBECS, BDENF, CINAHL e MEDLINE, e nas bibliotecas Cochrane e SciELO. Incluíram-se artigos de pesquisa original, produzidos com enfermeiros, sobre as práticas de enfermagem no contexto dos cuidados de saúde primários. Resultados: a revisão abrangeu trinta estudos publicados entre 2005 e 2014. Da análise, resultaram três categorias: práticas no serviço, práticas na comunidade e práticas de gestão e formação. Conclusão: os desafios dos enfermeiros são complexos, posto que o cuidado deve estar centrado nas necessidades de saúde da população, o que remete à ação para outros níveis de responsabilidade clínica e sanitária. A enfermagem brasileira mostra importantes avanços desde a implantação das políticas de reorganização do trabalho. Necessita, entretanto, avançar no que se refere ao deslocamento dos processos de trabalho, focados em procedimentos individuais, para um processo mais voltado aos usuários, onde a clínica ampliada seja o imperativo ético-político da organização dos serviços e da intervenção profissional.Objetivo: identificar y categorizar las prácticas ejercidas por los enfermeros en las Unidades Básicas y los Equipos de Salud de la Familia, desde el punto de vista de las atribuciones previstas por los marcos legales y programáticos de la profesión y del Sistema Único de la Salud. Método: se realizó una revisión de la literatura con el método scoping review, en las bases LILACS, IBECS, BDENF, CINAHL y MEDLINE, y en las bibliotecas Cochrane y SciELO. Se incluyeron artículos de investigación original, producidos con enfermeros, sobre las prácticas de enfermería en el contexto de los cuidados de salud primarios. Resultados: la revisión abarcó treinta estudios publicados entre 2005 y 2014. Del análisis, resultaron tres categorías: prácticas en el servicio; prácticas en la comunidad; y, prácticas de administración y formación. Conclusión: los desafíos de los enfermeros son complejos, ya que el cuidado debe estar centrado en las necesidades de salud de la población, lo que conduce a la acción para otros niveles de responsabilidad clínica y sanitaria. La enfermería brasileña muestra importantes avances a partir de la implantación de las políticas de reorganización del trabajo. Necesita, entre tanto, avanzar en lo que se refiere al desplazamiento de los procesos de trabajo, enfocados en procedimientos individuales, para un proceso más dirigido a los usuarios, en donde la clínica ampliada sea el imperativo ético político de la organización de los servicios y de la intervención profesional.info:eu-repo/semantics/publishedVersio