YPTB3816 of 'Yersinia pseudotuberculosis' strain IP32953 is a virulence-related metallo-oligopeptidase

Background: although bacterial peptidases are known to be produced by various microorganisms, including pathogenic bacteria, their role in bacterial physiology is not fully understood. In particular, oligopeptidases are thought to be mainly involved in degradation of short peptides e.g. leader peptides released during classical protein secretion pathways. The aim of this study was to investigate effects of inactivation of an oligopeptidase encoding gene opdA gene of Yersinia pseudotuberculosis on bacterial properties in vivo and in vitro, and to test dependence of the enzymatic activity of the respective purified enzyme on the presence of different divalent cations. Results: in this study we found that oligopeptidase OpdA of Yersinia pseudotuberculosis is required for bacterial virulence, whilst knocking out the respective gene did not have any effect on bacterial viability or growth rate in vitro. In addition, we studied enzymatic properties of this enzyme after expression and purification from E. coli. Using an enzyme depleted of contaminant divalent cations and different types of fluorescently labelled substrates, we found strong dependence of its activity on the presence of particular cations. Unexpectedly, Zn2+ showed stimulatory activity only at low concentrations, but inhibited the enzyme at higher concentrations. In contrast, Co2+, Ca2+ and Mn2+ stimulated activity at all concentrations tested, whilst Mg2+ revealed no effect on the enzyme activity at all concentrations used. Conclusions: the results of this study provide valuable contribution to the investigation of bacterial peptidases in general, and that of metallo-oligopeptidases in particular. This is the first study demonstrating that opdA in Yersinia pseudotuberculsosis is required for pathogenicity. The data reported are important for better understanding of the role of OpdA-like enzymes in pathogenesis in bacterial infections. Characterisation of this protein may serve as a basis for the development of novel antibacterials based on specific inhibition of this peptidase activity

Ligand-clustered “patchy” nanoparticles for modulated cellular uptake and in vivo tumor targeting

Author Manuscript: 2012 August 05.A matter of presentation: The manner in which polyvalent ligands are presented to a cell—homogeneously or in spatially defined groupings on a nanoparticle surface—may play an important role in cellular uptake. This aspect is investigated for the first time using a linear dendritic polymer construct to pattern the surfaces of nanoparticles with variable-sized ligand clusters in different spatial arrangements.National Institutes of Health (U.S.) (NIH NIBIB Grant 5R01EB008082-02)MIT-Harvard Center of Cancer Nanotechnology ExcellenceNational Science Foundation (U.S.

Transverse Electronic Transport through DNA Nucleotides with Functionalized Graphene Electrodes

Graphene nanogaps and nanopores show potential for the purpose of electrical DNA sequencing, in particular because single-base resolution appears to be readily achievable. Here, we evaluated from first principles the advantages of a nanogap setup with functionalized graphene edges. To this end, we employed density functional theory and the non-equilibrium Green's function method to investigate the transverse conductance properties of the four nucleotides occurring in DNA when located between the opposing functionalized graphene electrodes. In particular, we determined the electrical tunneling current variation as a function of the applied bias and the associated differential conductance at a voltage which appears suitable to distinguish between the four nucleotides. Intriguingly, we observe for one of the nucleotides a negative differential resistance effect.Comment: 19 pages, 7 figure

A Chronicle of Quantum Technologies in Game and Software Development

The ongoing second quantum revolution, marked by advancements harnessing quantum phenomena, has permeated various fields, including communications, computation, and networking, collectively known as quantum technologies (QT). Quantum computing, a focal point within QT, has led to the emergence of quantum games, a novel research and development area exploring creative applications of quantum computing in game development. While more than 300 quantum games have been developed by enthusiasts and commercial parties, a comprehensive research program or state-of-the-art review is notably absent. This paper addresses this gap by conducting a thorough literature review, presenting current advancements and examples in quantum games and interactive designs, and exploring future prospects for quantum technologies in game development practices

Don’t make me angry, you wouldn’t like me when I’m angry: volitional choices to act or inhibit are modulated by subliminal perception of emotional faces

Volitional action and self-control—feelings of acting according to one’s own intentions and in being control of one’s own actions—are fundamental aspects of human conscious experience. However, it is unknown whether high-level cognitive control mechanisms are affected by socially salient but nonconscious emotional cues. In this study, we manipulated free choice decisions to act or withhold an action by subliminally presenting emotional faces: In a novel version of the Go/NoGo paradigm, participants made speeded button-press responses to Go targets, withheld responses to NoGo targets, and made spontaneous, free choices to execute or withhold the response for Choice targets. Before each target, we presented emotional faces, backwards masked to render them nonconscious. In Intentional trials, subliminal angry faces made participants more likely to voluntarily withhold the action, whereas fearful and happy faces had no effects. In a second experiment, the faces were made supraliminal, which eliminated the effects of angry faces on volitional choices. A third experiment measured neural correlates of the effects of subliminal angry faces on intentional choice using EEG. After replicating the behavioural results found in Experiment 1, we identified a frontal-midline theta component—associated with cognitive control processes—which is present for volitional decisions, and is modulated by subliminal angry faces. This suggests a mechanism whereby subliminally presented “threat” stimuli affect conscious control processes. In summary, nonconscious perception of angry faces increases choices to inhibit, and subliminal influences on volitional action are deep seated and ecologically embedded

An Overview of Recommender Systems in the Internet of Things

The Internet Of Things (IoT) is an emerging paradigm that envisions a networked infrastructure enabling different types of devices to be interconnected. It creates different kinds of artifacts (e.g., services and applications) in various application domains such as health monitoring, sports monitoring, animal monitoring, enhanced retail services, and smart homes. Recommendation technologies can help to more easily identify relevant artifacts and thus will become one of the key technologies in future IoT solutions. In this article, we provide an overview of existing applications of recommendation technologies in the IoT context and present new recommendation techniques on the basis of real-world IoT scenarios

Crowdsourced mapping of unexplored target space of kinase inhibitors

Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound-kinase interactions for novel and potent activities. Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data. We find the top-performing predictions are based on various models, including kernel learning, gradient boosting and deep learning, and their ensemble leads to a predictive accuracy exceeding that of single-dose kinase activity assays. We design experiments based on the model predictions and identify unexpected activities even for under-studied kinases, thereby accelerating experimental mapping efforts. The open-source prediction algorithms together with the bioactivities between 95 compounds and 295 kinases provide a resource for benchmarking prediction algorithms and for extending the druggable kinome. The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts