Vaccination with DNA plasmids expressing Gn coupled to C3d or alphavirus replicons expressing Gn protects mice against rift valley fever virus

Background: Rift Valley fever (RVF) is an arthropod-borne viral zoonosis. Rift Valley fever virus (RVFV) is an important biological threat with the potential to spread to new susceptible areas. In addition, it is a potential biowarfare agent. Methodology/Principal Findings: We developed two potential vaccines, DNA plasmids and alphavirus replicons, expressing the Gn glycoprotein of RVFV alone or fused to three copies of complement protein, C3d. Each vaccine was administered to mice in an all DNA, all replicon, or a DNA prime/replicon boost strategy and both the humoral and cellular responses were assessed. DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited high titer neutralizing antibodies that were similar to titers elicited by the live-attenuated MP12 virus. Mice vaccinated with an inactivated form of MP12 did elicit high titer antibodies, but these antibodies were unable to neutralize RVFV infection. However, only vaccine strategies incorporating alphavirus replicons elicited cellular responses to Gn. Both vaccines strategies completely prevented weight loss and morbidity and protected against lethal RVFV challenge. Passive transfer of antisera from vaccinated mice into naïve mice showed that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn elicited antibodies that protected mice as well as sera from mice immunized with MP12. Conclusion/Significance: These results show that both DNA plasmids expressing Gn-C3d and alphavirus replicons expressing Gn administered alone or in a DNA prime/replicon boost strategy are effective RVFV vaccines. These vaccine strategies provide safer alternatives to using live-attenuated RVFV vaccines for human use. © 2010 Bhardwaj et al

The Distribution of gull Larus species on the Red Sea coast of Sudan

We present information on the status of gull species on the Red Sea coast of Sudan on the basis of observations made during a ten day visit to the region in January 2010. Seven gull taxa were recorded in this time. Sooty Larus hemprichii, Slender-billed L. genei, and Pallas’s L. ichthyaetus Gulls were all widespread along the coast, with Sooty Gull being the most abundant species encountered. Our sightings confirmed Pallas’s Gull as a winter visitor to this coast, and showed that Slender-billed Gull is widespread here. White-eyed L. leucophthalmus, Steppe L. (cachinnans) barabensis, Baltic L. fuscus fuscus, and Black-headed L. ridibundus Gulls were also encountered, but only around the harbours of Port Sudan and Suakin

Criança, violência e saúde: desafios e questões atuais

This paper examines challenges and current issues involved in measuring exposure to different types of violence which are associated mental health problems in children and adolescents. Standardized measures suitable for epidemiological studies, selected based on their relevance in the current literature, are briefly described and commented. The assessment of child's exposure to violence may focus on a specific event (e.g., kidnapping), a specific context (e.g., war) or even of a certain type of exposure (e.g., intrafamilial physical violence). The assessment of child mental health after exposure to violence has traditionally focused on posttraumatic stress disorder (PTSD) - most frequently measured through non-diagnostic scales. However, other mental health reactions may be present and screening as well as diagnostic instruments which may be used to assess these reactions are also described. Two issues of emerging importance - the assessment of impairment and of traumatic grief in children - are also presented. Availability of culturally appropriate instruments is a crucial step towards proper identification of child mental health problems after exposure to violence.Este artigo examina os desafios e perspectivas atuais envolvidos na mensuração da exposição a diferentes tipos de violência e problemas de saúde mental em crianças e adolescentes. Instrumentos padronizados apropriados para estudos epidemiológicos, selecionados com base em sua relevância na literatura, são brevemente descritos e comentados. A avaliação de exposição à violência em crianças pode dizer respeito a um evento específico (como sequestro) ou um contexto específico (como guerra) ou mesmo um determinado tipo de exposição (como violência física intrafamiliar). A avaliação da saúde mental infantil após a exposição à violência tradicionalmente concentrou-se na avaliação do transtorno de estresse pós-traumático (TEPT) - freqüentemente avaliado através de escalas não-diagnósticas. Porém, outras reações psicológicas podem ocorrer e instrumentos que podem ser usados para avaliar estas reações também são descritos neste artigo. Dois tópicos de importância emergente - a avaliação de prejuízo funcional e do pesar traumático em crianças - são também apresentados. Instrumentos culturalmente apropriados são essenciais para a identificação de problemas de saúde mental em crianças após a exposição à violência.Division of Child and Adolescent PsychiatryUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Departamento de PsiquiatriaUNIFESP, EPM, Depto. de PsiquiatriaSciEL

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

Data-Driven Understanding of Smart Service Systems Through Text Mining

Smart service systems are everywhere, in homes and in the transportation, energy, and healthcare sectors. However, such systems have yet to be fully understood in the literature. Given the widespread applications of and research on smart service systems, we used text mining to develop a unified understanding of such systems in a data-driven way. Specifically, we used a combination of metrics and machine learning algorithms to preprocess and analyze text data related to smart service systems, including text from the scientific literature and news articles. By analyzing 5,378 scientific articles and 1,234 news articles, we identify important keywords, 16 research topics, 4 technology factors, and 13 application areas. We define ???smart service system??? based on the analytics results. Furthermore, we discuss the theoretical and methodological implications of our work, such as the 5Cs (connection, collection, computation, and communications for co-creation) of smart service systems and the text mining approach to understand service research topics. We believe this work, which aims to establish common ground for understanding these systems across multiple disciplinary perspectives, will encourage further research and development of modern service systems

Differential branching fraction and angular analysis of Λb0→Λμ+μ−\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^- decays

The differential branching fraction of the rare decay $\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-$ is measured as a function of $q^{2}$, the square of the dimuon invariant mass. The analysis is performed using proton-proton collision data, corresponding to an integrated luminosity of 3.0 \mbox{ fb}^{-1}, collected by the LHCb experiment. Evidence of signal is observed in the $q^2$ region below the square of the $J/\psi$ mass. Integrating over 15 < q^{2} < 20 \mbox{ GeV}^2/c^4 the branching fraction is measured as d\mathcal{B}(\Lambda^{0}_{b} \rightarrow \Lambda \mu^+\mu^-)/dq^2 = (1.18 ^{+ 0.09} _{-0.08} \pm 0.03 \pm 0.27) \times 10^{-7} ( \mbox{GeV}^{2}/c^{4})^{-1}, where the uncertainties are statistical, systematic and due to the normalisation mode, $\Lambda^{0}_{b} \rightarrow J/\psi \Lambda$, respectively. In the $q^2$ intervals where the signal is observed, angular distributions are studied and the forward-backward asymmetries in the dimuon ($A^{l}_{\rm FB}$) and hadron ($A^{h}_{\rm FB}$) systems are measured for the first time. In the range 15 < q^2 < 20 \mbox{ GeV}^2/c^4 they are found to be A^{l}_{\rm FB} = -0.05 \pm 0.09 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)} and A^{h}_{\rm FB} = -0.29 \pm 0.07 \mbox{ (stat)} \pm 0.03 \mbox{ (syst)}.Comment: 27 pages, 10 figures, Erratum adde

The conserved C-terminus of the PcrA/UvrD helicase interacts directly with RNA polymerase

Copyright: © 2013 Gwynn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a Wellcome Trust project grant to MD (Reference: 077368), an ERC starting grant to MD (Acronym: SM-DNA-REPAIR) and a BBSRC project grant to PM, NS and MD (Reference: BB/I003142/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Microdevices for extensional rheometry of low viscosity elastic liquids : a review

Extensional flows and the underlying stability/instability mechanisms are of extreme relevance to the efficient operation of inkjet printing, coating processes and drug delivery systems, as well as for the generation of micro droplets. The development of an extensional rheometer to characterize the extensional properties of low viscosity fluids has therefore stimulated great interest of researchers, particularly in the last decade. Microfluidics has proven to be an extraordinary working platform and different configurations of potential extensional microrheometers have been proposed. In this review, we present an overview of several successful designs, together with a critical assessment of their capabilities and limitations

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae

The benzylisoquinoline alkaloids (BIAs) are a diverse class of metabolites that exhibit a broad range of pharmacological activities and are synthesized through plant biosynthetic pathways comprised of complex enzyme activities and regulatory strategies. We have engineered yeast to produce the key intermediate reticuline and downstream BIA metabolites from a commercially available substrate. An enzyme tuning strategy was implemented that identified activity differences between variants from different plants and determined optimal expression levels. By synthesizing both stereoisomer forms of reticuline and integrating enzyme activities from three plant sources and humans, we demonstrated the synthesis of metabolites in the sanguinarine/berberine and morphinan branches. We also demonstrated that a human P450 enzyme exhibits a novel activity in the conversion of (R)-reticuline to the morphinan alkaloid salutaridine. Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches