207 research outputs found

    Strain-specific activation of the NF-kappa B pathway by GRA15, a novel Toxoplasma gondii dense granule protein

    No full text
    NF-κB is an integral component of the immune response to Toxoplasma gondii. Although evidence exists that T. gondii can directly modulate the NF-κB pathway, the parasite-derived effectors involved are unknown. We determined that type II strains of T. gondii activate more NF-κB than type I or type III strains, and using forward genetics we found that this difference is a result of the polymorphic protein GRA15, a novel dense granule protein which T. gondii secretes into the host cell upon invasion. A GRA15-deficient type II strain has a severe defect in both NF-κB nuclear translocation and NF-κB–mediated transcription. Furthermore, human cells expressing type II GRA15 also activate NF-κB, demonstrating that GRA15 alone is sufficient for NF-κB activation. Along with the rhoptry protein ROP16, GRA15 is responsible for a large part of the strain differences in the induction of IL-12 secretion by infected mouse macrophages. In vivo bioluminescent imaging showed that a GRA15-deficient type II strain grows faster compared with wild-type, most likely through its reduced induction of IFN-γ. These results show for the first time that a dense granule protein can modulate host signaling pathways, and dense granule proteins can therefore join rhoptry proteins in T. gondii’s host cell–modifying arsenal.American Heart Association (Scientist Development Grant 0835099N)Massachusetts Life Sciences CenterSingapore. Agency for Science, Technology and ResearchNational Institutes of Health (U.S.) (AI080621)Cleo and Paul Schimmel FoundationCancer Research Institute (New York, N.Y.

    Persona?based development of a new discovery system using MERESCO open?source components

    No full text
    Sophie and Rogier are students at Delft University of Technology. Sophie is a master student of Architecture. She searches for information mostly to get inspired. Sometimes she’s looking for a specific book and uses Amazon first, because she knows what the cover looks like, but can’t remember the author or title. Rogier is writing his master’s thesis at the faculty of Civil Engineering. He searches the library for relevant publications. He is very insecure about the search results he’s getting back from the library catalogue and various bibliographic databases. Did he get the key publications? TU Delft Library’s websites and databases are not supporting either Sophie or Rogier’s needs. Sophie and Rogier are fictional customers of TU Delft Library. They are personas constructed from a context mapping study. Six different personas give our customers voices and faces. They help us specify the services and systems that our customers expect now and in the future, such as Discover (http://discover.tudelft.nl) which will replace the traditional WebOPAC. With Discover, Sophie and Rogier can use Google-like queries and drilldown facets to find both books from the catalogue and full text articles (from Elsevier, DOAJ, Repositories and more). Records are enriched with cover images, abstracts, user ratings and LibraryThing tags. Discover is built with Meresco open source component library, which uses the Lucene search engine.Library TU DelftDelft University of Technolog

    Author Correction: Toddlers strategically adapt their information search

    No full text
    Correction to: Nature Communicationshttps://doi.org/10.1038/s41467-024-48855-4, published online 10 July 2024 In this article the affiliation ‘Max Planck Research Group iSearch, Max Planck Institute for Human Development, Berlin, Germany’ was incorrectly given for Rogier Mars but should have been removed. In addition, the affiliation ‘Wellcome Centre for Integrative Neuroimaging, Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, UK’ was incorrectly given for Azzurra Ruggeri but should have been ‘Max Planck Research Group iSearch, Max Planck Institute for Human Development, Berlin, Germany’. The original article has been corrected

    Correction to: Severe Dysbiosis and Specific Haemophilus and Neisseria Signatures as Hallmarks of the Oropharyngeal Microbiome in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients

    No full text
    This is a pre-copyedited, author-produced PDF of an article accepted for publication in Clinical Infectious Diseases following peer review. The version of record, Juliana de Castilhos, PhD, Eli Zamir, PhD, Theresa Hippchen, MD, Roman Rohrbach, Sabine Schmidt, Silvana Hengler, Hanna Schumacher, Melanie Neubauer, Sabrina Kunz, Tonia Müller-Esch, Andreas Hiergeist, PhD, André Gessner, MD PhD, Dina Khalid, MD, Rogier Gaiser, PhD, Nyssa Cullin, PhD, Stamatia M Papagiannarou, Bettina Beuthien-Baumann, MD, Alwin Krämer, MD, Ralf Bartenschlager, PhD, Dirk Jäger, MD, Michael Müller, MD, Felix Herth, MD, Daniel Duerschmied, MD, Jochen Schneider, MD, Roland M Schmid, MD, Johann F Eberhardt, Yascha Khodamoradi, MD, Maria J G T Vehreschild, MD, Andreas Teufel, MD, Matthias P Ebert, MD, Peter Hau, MD, Bernd Salzberger, MD, Paul Schnitzler, PhD, Hendrik Poeck, MD, Eran Elinav, MD PhD, Uta Merle, MD, Christoph K Stein-Thoeringer, MD, Severe dysbiosis and specific Haemophilus and Neisseria signatures as hallmarks of the oropharyngeal microbiome in critically ill COVID-19 patients, Clinical Infectious Diseases, 2021;, ciab902, https://doi.org/10.1093/cid/ciab902, is available online at: https://doi.org/10.1093/cid/ciab902. Deposited by shareyourpaper.org and openaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailing [email protected]

    Le Peire Rogier de Peire d’Alvernhe revisité par l’auteur de Flamenca : Guillem de Nevers, le troubadour au psautier

    No full text
    S’il a été établi que les paroles constitutives du dialogue amoureux entre les personnages du roman, Guillem de Nevers et Flamenca, prenaient leur source dans les vers de Peire Rogier (Ges non puesc en bon vers fallir, sixième cobla) ou encore dans ceux, inspirés du précédent, de Guiraut de Borneil (̶ Ai las, com mor ! – Quez as, amis ?), le lien entre Guillem de Nevers et Peire Rogier apparaît davantage évident si l’on prend en compte la vida de ce dernier ainsi que la cobla que lui consacre Peire d’Alvernhe dans sa chanson satirique Cantarai d’aqestz trobadors. Dans cette chanson, une partie du conseil de Peire d’Alvernhe à Peire Rogier – à savoir qu’au lieu de chanter l’amour devant tous, il devrait tenir un psautier à l’église ̶ resserre d’autant plus les liens entre le troubadour et le personnage du roman. Il semble que l’auteur de Flamenca se soit amusé à fondre dans son personnage le troubadour Peire Rogier afin de lui faire suivre les conseils de Peire d’Alvernhe mais en redirigeant la satire – qui visait le troubadour dans la chanson  ̶ , vers la société religieuse et, en apparence, courtoise de son roman : il instaure un jeu particulièrement ingénieux autour de la symbolique du psautier et de celle de l’homme religieux. En effet, l’auteur s’amuse à faire de Guillem un clerc dont l’ordination n’a pas d’autre raison que l’amour qu’il éprouve pour Flamenca comme il s’amuse à faire du livre sacré le support où Guillem lit – par le biais de la bibliomancie – l’avenir de son amour avec Flamenca, le support par lequel les baisers de paix préfigurent les baisers amoureux, le support au-dessus duquel il échange les mots d’amour avec Flamenca. L’auteur s’ingénie ainsi à recouvrir les mots et les gestes sacrés par les mots et les gestes de la fin’amor afin de nous laisser entendre que le sacré est à trouver dans les valeurs de cette dernière qui elles-mêmes – puisque, dans cette société qui n’a de courtoise que le nom, elles ne peuvent s’accomplir que par la ruse et la dissimulation – n’ont peut-être pas d’autre avenir que dans les sphères de la fiction.Although it has been established that the words that make up the love dialogue between the novel’s characters, Guillem de Nevers and Flamenca, originated in Peire Rogier’s verses (Ges non puesc en bon vers fallir, sixth cobla) or in those, inspired by the former, by Guiraut de Borneil (– Ai las, com mor ! – Quez as, amis ?), the link between Guillem de Nevers and Peire Rogier becomes even more obvious if we take into account the latter’s vida and the cobla dedicated to him by Peire d’Alvernhe in his satirical song Cantarai d’aqestz trobadors. In this song, part of Peire d’Alvernhe’s advice to Peire Rogier – namely, that instead of singing about love in front of everyone, he should hold a psalter in church ̶ further tightens the ties between the troubadour and the character in the novel. It seems that the author of Flamenca had fun fusing the troubadour Peire Rogier into his character in order to have him follow Peire d’Alvernhe’s advice, but redirecting the satire – which was aimed at the troubadour in the song –, towards the religious and, seemingly, courteous society of his novel : he sets up a particularly ingenious game about the symbolism of the psalter and that of the religious man. Indeed, the author amuses himself by making Guillem a cleric whose ordination has no other reason than the love he feels for Flamenca and by making the holy book the medium in which Guillem is able to foresee ̶ through bibliomancy  ̶ his love for Flamenca ; the medium also by which peace kisses foreshadow love kisses, and over which he exchanges words of love with Flamenca. In this way, the author ingeniously covers the sacred words and gestures with the ones of the fin’amor in order to suggest to us that the sacred is to be found in the values of the latter, which themselves – since, in this society which is courteous in name only, they can only be accomplished by cunning and dissimulation – perhaps have no other future than in the spheres of fiction

    Adaptive deformable mirror dynamics and modular control

    No full text
    The refractive index of air varies a.o. with temperature, humidity, pressure and the CO2 concentration. Due to atmospheric turbulence this refractive index varies both in space and in time, leading to aberrations in images of light having passed though it. These aberrations limit the achievable resolution of optical telescopes such that the quality of their images is no longer diffraction limited. An adaptive optics (AO) system is a means to recover the diffraction limited quality of the images. This can be achieved a.o. by reflecting the incoming light on a deformable mirror (DM) that adapts its shape to the wavefront of this light such that some norm of the residual wavefront after reflection is minimal. In this thesis novel designs are considered for the DM and its control system. They are primarily aimed at the 8m class of telescopes in visible light, leading to a 200Hz controller bandwidth requirement and 6mm actuator spacing or 5000 actuators on a 500mm diameter DM.. To observe fainter celestial objects and/or increase the image resolution, optical telescopes are foreseen with primary mirrors of up to 40m in diameter. Therefore, the DM system design is aimed at extendibility to a larger number of Degrees Of Freedom (DOF), which is realized using a modular concept. Other drivers are low power consumption to prevent the need for active cooling systems and low production costs. The DM design is realized using electromagnetic reluctance type actuators that are connected to the DM's reflective membrane by a thin rod. Modules containing 61 hexagonally arranged actuators are manufactured using techniques suitable for mass-production. To generate the currents through the actuator coils, driver electronics are developed based on Pulse-Width Modulation (implemented in FPGAs) in combination with analog low-pass filters. Several prototype DMs are realized whose behavior is analyzed both statically and dynamically by comparing Wyko and laser vibrometer measurements with first principle models of the driver electronics, the actuators and the facesheet. To retain modularity of the system, a distributed control system architecture is foreseen in which each (group of) actuator(s) has its own controller that has a fixed computational power, communicates only to its neighbors and receives only a subset of the wavefront measurement data. The design of a distributed controller with good performance is complicated by the wavefront reconstruction step made necessary by the Shack-Hartmann wavefront sensor. Nevertheless, a distributed algorithm that combines wavefront reconstruction with adaptive prediction is shown in simulation to approximate the performance of a centralized finite impulse response (FIR) predictor/reconstructor and does not deteriorate as the number of DOFs increases.DCSCMechanical, Maritime and Materials Engineerin

    Production of eukaryotic antimicrobial peptides by bacteria A review.

    No full text
    11 páginas, 2 tablas -- PAGS nros. 978-988The alarming increase in incidence of multidrug-resistant, pathogenic bacteria, the paucity in the discovery of new antibiotic leads, and the resulting public health risk have recently heightened interest in naturally occurring antimicrobial peptides (AMPs) as potential novel therapeutics. [1, 2] Higher organisms are equipped with an innate immune system that allows them to fight invading pathogens. Antimicrobial peptides, also referred to as host-defense peptides (HDP) [3], are gene-encoded, small effector molecules of the innate immune system, which play a major role as the first chemical barrier against invading pathogens. Their characteristic features are broad-spectrum antimicrobial activity and constitutive expression or fast induction after pathogen challenge. [4] Usually ranging between 13-45 amino acid residues long, these peptides share a net positive charge and amphipathic 3D structures (displaying both hydrophilic and hydrophobic areas), despite the large variety of their primary sequences. [5, 6] Three major families of AMPs have been described in humans: cathelicidins, defensins, and histatins. Overall, more than 1,200 AMP sequences have been reported from animals and plants. [7, 8] The heterologous expression of eukaryotic antimicrobial peptides (EAPs) by microorganisms could be a costeffective tool for functional and clinical research. The use of bacteria as cell-factories is interesting due to the possibility of isolating and purifying secreted proteins. [9] The Gram-positive lactic acid bacteria (LAB) have a generallyregarded- as-safe (GRAS)-status, and are widely employed in human food production, with a long history of safe use in a variety of fermentation processes. [10] Several studies have been performed on the use of LAB as mucosal delivery vehicles of heterologous proteins, such as vaccine antigens or therapeutic agents. [11, 12, 13] Recent advances in inducible promoters and selection markers in food-grade organisms open up possibilities to select safe organisms as probiotics. [14] This review focuses on currently available systems for the heterologous expression of functionally active eukaryotic antimicrobial peptides by bacteria, with a focus on potential future applications in LABRA Gaiser is supported by a EU Marie Curie fellowship within the FP7 Initial Training Network, grant no. 238490.Peer reviewe

    Antimicrobial peptides and the interplay between microbes and host : towards preventing porcine infections with Streptococcus suis

    No full text
    The increasing prevalence of antibiotic resistance in pathogenic bacteria and the potential future implications for human and animal morbidity and mortality, health-care costs and economic losses pose an urgent worldwide problem. As a result, exploration of alternative strategies to combat antibiotic resistant bacteria have intensified over the last decades. The work described in this thesis focused on the study of naturally occurring antimicrobial peptides (AMPs) and other bioactive molecules produced by bacteria as potential alternatives to prevent or treat infections with pathogenic bacteria. A large part of the thesis aimed to increase knowledge about the role of the microbiota (the collection of microbes present at a certain location of the body) of the oral cavity or small intestine in the abundance of Streptococcus suis, a pathogenic bacteria that mostly causes disease in young pigs. We identified commensal bacteria that displayed strong and selective antagonism against this S. suis. Several bacteria that showed strong growth inhibition of S. suis in the lab through the production of AMPs were isolated and characterised. This thesis increased the understanding of the role of host- and microbiota-derived biologically active small molecules in microbe-microbe and microbe-host interplay. Such knowledge may contribute to the development of novel therapeutic solutions to treat antibiotic resistant bacteria, such as beneficial microbial communities (i.e. next-generation probiotics) or biotechnological applications of natural or modified AMPs

    Modeling mind and matter: reductionism and psychological measurement in cognitive neuroscience

    No full text
    The article presents the author's response to an article related to reductionism and psychological measurement in cognitive neuroscience by Rogier A. Kievit and Denny Borsboom, published in a previous issue of the periodical. The author says that the commentaries by the writers in the article suggests that the implementation of conceptually guided psychometric models is viable. He also focuses on the relation between people and reductionism mentioned by the writers in the article

    Anleitung Zu der Frantzösischen Sprach/ Begreiffend was anfänglich/ diese Sprach zuerlernen/ am allernöhtigsten sey: Der Jugend Teutscher Nation: zu besten verfertiget

    No full text
    ANLEITUNG ZU DER FRANTZÖSISCHEN SPRACH/ BEGREIFFEND WAS ANFÄNGLICH/ DIESE SPRACH ZUERLERNEN/ AM ALLERNÖHTIGSTEN SEY: DER JUGEND TEUTSCHER NATION: ZU BESTEN VERFERTIGET Anleitung Zu der Frantzösischen Sprach/ Begreiffend was anfänglich/ diese Sprach zuerlernen/ am allernöhtigsten sey: Der Jugend Teutscher Nation: zu besten verfertiget Anleitung Zu der Frantzösischen Sprach/ Begreiffend was anfänglich/ diese Sprach zuerlernen/ am allernöhtigsten sey: Der Jugend Teutscher Nation: zu besten verfertiget (Theil 2) ([1]r) Anleitung Zu der Frantzösischen Sprach/ Begreiffend was anfänglich/ diese Sprach zuerlernen/ am allernöhtigsten sey: Der Jugend Teutscher Nation: zu besten verfertiget (Forts.) ([1]r
    corecore