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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Zheng, Yue; Tsuji, Genichiro; Opoku-Temeng, Clement; Sintim, Herman O.;

    Various important cellular processes in bacteria are controlled by c-di-GMP, such as motility, biofilm formation and virulence factors production. C-di-GMP is synthesized from two molecules of GTP by diguanylate cyclases (DGCs) and its actions are terminated by EAL or HD-GYP domain phosphodiesterases (PDEs), which hydrolyze c-di-GMP to linear pGpG or GMP. Thus far the majority of efforts have been dedicated to the development of inhibitors of DGCs but not PDEs. This is probably because the old view was that inhibiting any c-di-GMP PDE would lead to biofilm formation, an undesirable phenotype. Recent data however suggest that some PDEs only change the localized (not global) concentration of c-di-GMP to increase bacterial virulence and do not affect biofilm formation. A challenge therefore is to be able to develop selective PDE inhibitors that inhibit virulence-associated PDEs but not inhibit PDEs that regulate bacterial biofilm formation. Using high throughput docking experiments to screen a library of 250 000 commercially available compounds against E. coli YahA (also called PdeL), a benzoisothiazolinone derivative was found to bind to the c-di-GMP binding site of YahA with favorable energetics. Paradoxically the in silico identified inhibitor (a benzoisothiazolinone derivative) did not inhibit the hydrolysis of c-di-GMP by YahA, the model PDE that was used in the docking, but instead inhibited RocR, which is a PDE from the opportunistic pathogen P. aeruginosa (PA). RocR promotes bacterial virulence but not biofilm dispersal, making it an ideal PDE to target for anti-virulence purposes. This newly identified RocR ligand displayed some selectivity and did not inhibit other P. aeruginosa PDEs, such as DipA, PvrR and PA4108. DipA, PvrR and PA4108 are key enzymes that reduce global c-di-GMP concentration and promote biofilm dispersal; therefore the identification of an inhibitor of a PA PDE, such as RocR, that does not inhibit major PDEs that modulate global c-di-GMP is an important step towards the development of selective c-di-GMP PDEs that could have interesting biomedical applications. The identified RocR ligand could also inhibit P. aeruginosa (PAO1) swarming but not swimming or biofilm formation. Rhamnolipid production was decreased, explaining the inhibition of swarming. Pseudomonas aeruginosa swarming motility can be inhibited with a small molecule inhibitor of c-di-GMP phosphodiesterase, RocR.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Article . 2016
    Data sources: PubMed Central
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Article . 2016
      Data sources: PubMed Central
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Fansheng Kong; Rui Gao; Stephen S Gao; Kelly H Liu; +11 Authors

    ABSTRACT It has long been established that plastic flow in the asthenosphere interacts constantly with the overlying lithosphere and plays a pivotal role in controlling the occurrence of geohazards such as earthquakes and volcanic eruptions. Unfortunately, accurately characterizing the direction and lateral extents of the mantle flow field is notoriously difficult, especially in oceanic areas where deployment of ocean bottom seismometers (OBSs) is expensive and thus rare. In this study, by applying shear wave splitting analyses to a dataset recorded by an OBS array that we deployed between mid-2019 and mid-2020 in the South China Sea (SCS), we show that the dominant mantle flow field has a NNW–SSE orientation, which can be attributed to mantle flow extruded from the Tibetan Plateau by the ongoing Indian–Eurasian collision. In addition, the results suggest that E–W oriented flow fields observed in South China and the Indochina Peninsula do not extend to the central SCS.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ National Science Rev...arrow_drop_down
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    National Science Review
    Article . 2023
    License: CC BY
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      National Science Review
      Article . 2023
      License: CC BY
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Akash Gupta; Ryan F. Landis; Vincent M. Rotello;

    Bacterial infections cause 300 million cases of severe illness each year worldwide. Rapidly accelerating drug resistance further exacerbates this threat to human health. While dispersed (planktonic) bacteria represent a therapeutic challenge, bacterial biofilms present major hurdles for both diagnosis and treatment. Nanoparticles have emerged recently as tools for fighting drug-resistant planktonic bacteria and biofilms. In this review, we present the use of nanoparticles as active antimicrobial agents and drug delivery vehicles for antibacterial therapeutics. We further focus on how surface functionality of nanomaterials can be used to target both planktonic bacteria and biofilms.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ F1000Researcharrow_drop_down
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    F1000Research
    Article . 2016
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      F1000Research
      Article . 2016
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  • Authors: Kaoru Takahashi; Takashi Sako; Keitaro Fujita; Kozo Fujisue; +5 Authors
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Sebastian Krogh;
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ https://hess.coperni...arrow_drop_down
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    Review
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ https://hess.coperni...arrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Katherine G Schaefer; Charles M Russell; Andrew Dixson; Amber LH Gray; +9 Authors

    Candida albicans causes severe invasive candidiasis. C. albicans infection requires the virulence factor candidalysin (CL) which damages target cell membranes. However, the mechanism that CL uses to permeabilize membranes is unclear. We reveal that CL forms membrane pores using a unique mechanism. Unexpectedly, CL readily assembled into polymers in solution. We propose that the basic structural unit in polymer formation is a CL oligomer, which is sequentially added into a string configuration that can close into a loop. CL loops appear to spontaneously insert into the membrane to become pores. A CL mutation (G4W) inhibited the formation of polymers in solution and prevented pore formation in synthetic lipid systems. Epithelial cell studies showed that G4W CL failed to activate the danger response pathway, a hallmark of the pathogenic effect of CL. These results indicate that CL polymerization in solution is a necessary step for the damage of cellular membranes. Analysis of CL pores by atomic force microscopy revealed co-existence of simple depressions and more complex pores, which are likely formed by CL assembled in an alternate oligomer orientation. We propose that this structural rearrangement represents a maturation mechanism that stabilizes pore formation to achieve more robust cellular damage. To summarize, CL uses a previously unknown mechanism to damage membranes, whereby pre-assembly of CL loops in solution leads to formation of membrane pores. Our investigation not only unravels a new paradigm for the formation of membrane pores, but additionally identifies CL polymerization as a novel therapeutic target to treat candidiasis.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ eLifearrow_drop_down
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    eLife
    Article . 2022
    License: CC BY
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      eLife
      Article . 2022
      License: CC BY
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Joan L. Welc; Lay Thorne;

    Abstract The Banda Sea earthquake of November 4, 1963 is one of the largest ( M w = 8.3) intraplate events. It involved oblique thrusting at an intermediate depth within the subducted lithosphere near the abrupt bend in the southeastern Banda arc (6.86° S, 129.58° E). To better understand the tectonic significance of this earthquake, the detailed source process of the Banda Sea event was determined by body wave analysis. The rupture history was established by deconvolving source time functions from long-period P wave seismograms, using both individual station and multi-station time-domain deconvolution methods. The seismic moment release occurred within the first 50 s of rupture, initiating at a depth near 120 km and expanding laterally and downdip over a vertical extent of about 50 km. Slip and moment release were concentrated in one main region near the hypocenter, at depths between 110 and 130 km. The along-strike rupture length was only about 100 km, so it is difficult to resolve any horizontal directivity. The compressional stress orientation inferred from the focal mechanism parallels the strike of the slab, and reflects the importance of contortion of the lithosphere in this region. The Banda Sea event may be part of a major detachment at the leading edge of the subducted Australian continental shelf.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Physics of The Earth...arrow_drop_down
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    Physics of The Earth and Planetary Interiors
    Article . 1987
    License: Elsevier TDM
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      Physics of The Earth and Planetary Interiors
      Article . 1987
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    Authors: Leah, Kulp; Aleksandra, Sarcevic; Megan, Cheng; Yinan, Zheng; +1 Authors

    This mixed-methods study examines the effects of a tablet-based checklist system on team performance during a dynamic and safety-critical process of trauma resuscitation. We compared team performance from 47 resuscitations that used a paper checklist to that from 47 cases with a digital checklist to determine if digitizing a checklist led to improvements in task completion rates and in how fast the tasks were initiated for 18 most critical assessment and treatment tasks. We also compared if the checklist compliance increased with the digital design. We found that using the digital checklist led to more frequent completions of the initial airway assessment task but fewer completions of ear and lower extremities exams. We did not observe any significant differences in time to task performance, but found increased compliance with the checklist. Although improvements in team performance with the digital checklist were minor, our findings are important because they showed no adverse effects as a result of the digital checklist introduction. We conclude by discussing the takeaways and implications of these results for effective digitization of medical work.

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    https://dl.acm.org/doi/pdf/10....
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    Europe PubMed Central
    Other literature type . 2019
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    https://doi.org/10.1145/329060...
    Conference object . 2019
    License: ACM Copyright Policies
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      Europe PubMed Central
      Other literature type . 2019
      Data sources: PubMed Central
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      https://doi.org/10.1145/329060...
      Conference object . 2019
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    Authors: Jinghua Yang; Aykut Dengi; Sarma Vrudhula;

    Systems powered by harvested energy must consume very low power and withstand frequent interruptions in power. Nonvolatile logic (NVL) addresses the latter by saving the system state in flipflops enhanced with spin-transfer torque magnetic tunnel junctions (STT-MTJs) as the nonvolatile storage devices. Manufacturing variations in the STT-MTJs and in CMOS transistors significantly reduce yield, leading to overdesign and high-energy consumption. A detailed analysis of the design tradeoffs in the driver circuitry for performing backup and restore, and a novel method to design the energy optimal driver for a given yield is presented. Next, efficient designs of two nonvolatile flip-flop (NVFF) circuits are presented, in which the backup time is determined on a per-chip basis, resulting in minimizing the energy wastage and satisfying the yield constraint. To achieve a yield of 98%, the conventional approach would have to expend nearly $5\times $ more energy than the minimum required, whereas the proposed tunable approach expends only 26% more energy than the minimum. Also included are the energy consumption of the proposed NVFF designs when used in two larger function blocks. Experimental results were based on a commercial 40-nm process design kit, and HSPICE simulations with foundry supplied statistical models and data.

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    Authors: Villaverde, Tamara; Global Carex Group;

    Carex (Cyperaceae), with an estimated 2000 species, nearly cosmopolitan distribution and broad range of habitats, is one of the largest angiosperm genera and the largest in the temperate zone. In this article, we provide argument and evidence for a broader circumscription of Carex to add all species currently classified in Cymophyllus (monotypic), Kobresia (c. 60 species), Schoenoxiphium (c. 15 species) and Uncinia (c. 70 species) to those currently classified as Carex. Carex and these genera comprise tribe Cariceae (subfamily Cyperoideae, Cyperaceae) and form a wellsupported monophyletic group in all molecular phylogenetic studies to date. Carex as defined here in the broad sense currently comprises at least four clades. Three are strongly supported (Siderostictae, core Vignea and core Carex), whereas the caricoid clade, which includes all the segregate genera, receives only weak to moderate support. The caricoid clade is most commonly split into two clades, one including a monophyletic Schoenoxiphium and two small clades of species of Carex s.s., and the other comprising Kobresia, Uncinia and mostly unispicate species of Carex s.s. Morphological variation is high in all but the Vignea clade, making it extremely difficult to define consistent synapomorphies for most clades. However, Carex s.l. as newly circumscribed here is clearly differentiated from the sister groups in tribe Scirpeae by the transition from bisexual flowers with a bristle perianth in the sister group to unisexual flowers without a perianth in Carex. The naked female flowers of Carex s.l. are at least partially enclosed in a flask-shaped prophyll, termed a perigynium. Carex s.s. is not only by far the largest genus in the group, but also the earliest published name. As a result, only 72 new combinations and 58 replacement names are required to treat all of tribe Cariceae as a single genus Carex. We present the required transfers here, with synonymy, and we argue that this broader monophyletic circumscription of Carex reflects the close evolutionary relationships in the group and serves the goal of nomenclatural stability better than other possible treatments. We are grateful to the John D. and Catherine T. MacArthur Foundation for funding of the Biodiversity Synthesis Group of the Encyclopedia of Life (EOL) project, which funded our BioSynC Synthesis meeting at the Field Museum in Chicago in September 2011, when the Global Carex Group was formed. We also thank the US National Science Foundation (NSF) for funding our continuing international collaborative work on the phylogeny and classification of Carex under grants DEB 1255901 to ALH and MJW, and DEB 1256033 to EHR. We also acknowledge with thanks funding for nomenclatural research and for attendance at our second meeting during the Monocots V conference in New York in July, 2013, from the Natural Sciences and Engineering Research Council, Canada (NSERC) to MJW and JRS; University of Mainz to BG; JSPS KAKENHI Grant no. 25840136 to OY; Korea National Arboretum to SK; CGL2012- 38744 project from the Spanish Ministry of Economy and Competitiveness to ML; project 30870178 from the National Natural Science Foundation of China to SRZ, and a University of Wisconsin-Madison Raper Travel Grant to DS. The figures were prepared with invaluable technical advice from H. C. Rimmer. Peer reviewed

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    Authors: Zheng, Yue; Tsuji, Genichiro; Opoku-Temeng, Clement; Sintim, Herman O.;

    Various important cellular processes in bacteria are controlled by c-di-GMP, such as motility, biofilm formation and virulence factors production. C-di-GMP is synthesized from two molecules of GTP by diguanylate cyclases (DGCs) and its actions are terminated by EAL or HD-GYP domain phosphodiesterases (PDEs), which hydrolyze c-di-GMP to linear pGpG or GMP. Thus far the majority of efforts have been dedicated to the development of inhibitors of DGCs but not PDEs. This is probably because the old view was that inhibiting any c-di-GMP PDE would lead to biofilm formation, an undesirable phenotype. Recent data however suggest that some PDEs only change the localized (not global) concentration of c-di-GMP to increase bacterial virulence and do not affect biofilm formation. A challenge therefore is to be able to develop selective PDE inhibitors that inhibit virulence-associated PDEs but not inhibit PDEs that regulate bacterial biofilm formation. Using high throughput docking experiments to screen a library of 250 000 commercially available compounds against E. coli YahA (also called PdeL), a benzoisothiazolinone derivative was found to bind to the c-di-GMP binding site of YahA with favorable energetics. Paradoxically the in silico identified inhibitor (a benzoisothiazolinone derivative) did not inhibit the hydrolysis of c-di-GMP by YahA, the model PDE that was used in the docking, but instead inhibited RocR, which is a PDE from the opportunistic pathogen P. aeruginosa (PA). RocR promotes bacterial virulence but not biofilm dispersal, making it an ideal PDE to target for anti-virulence purposes. This newly identified RocR ligand displayed some selectivity and did not inhibit other P. aeruginosa PDEs, such as DipA, PvrR and PA4108. DipA, PvrR and PA4108 are key enzymes that reduce global c-di-GMP concentration and promote biofilm dispersal; therefore the identification of an inhibitor of a PA PDE, such as RocR, that does not inhibit major PDEs that modulate global c-di-GMP is an important step towards the development of selective c-di-GMP PDEs that could have interesting biomedical applications. The identified RocR ligand could also inhibit P. aeruginosa (PAO1) swarming but not swimming or biofilm formation. Rhamnolipid production was decreased, explaining the inhibition of swarming. Pseudomonas aeruginosa swarming motility can be inhibited with a small molecule inhibitor of c-di-GMP phosphodiesterase, RocR.

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    Europe PubMed Central
    Article . 2016
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      Europe PubMed Central
      Article . 2016
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    Authors: Fansheng Kong; Rui Gao; Stephen S Gao; Kelly H Liu; +11 Authors

    ABSTRACT It has long been established that plastic flow in the asthenosphere interacts constantly with the overlying lithosphere and plays a pivotal role in controlling the occurrence of geohazards such as earthquakes and volcanic eruptions. Unfortunately, accurately characterizing the direction and lateral extents of the mantle flow field is notoriously difficult, especially in oceanic areas where deployment of ocean bottom seismometers (OBSs) is expensive and thus rare. In this study, by applying shear wave splitting analyses to a dataset recorded by an OBS array that we deployed between mid-2019 and mid-2020 in the South China Sea (SCS), we show that the dominant mantle flow field has a NNW–SSE orientation, which can be attributed to mantle flow extruded from the Tibetan Plateau by the ongoing Indian–Eurasian collision. In addition, the results suggest that E–W oriented flow fields observed in South China and the Indochina Peninsula do not extend to the central SCS.

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    National Science Review
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    Authors: Akash Gupta; Ryan F. Landis; Vincent M. Rotello;

    Bacterial infections cause 300 million cases of severe illness each year worldwide. Rapidly accelerating drug resistance further exacerbates this threat to human health. While dispersed (planktonic) bacteria represent a therapeutic challenge, bacterial biofilms present major hurdles for both diagnosis and treatment. Nanoparticles have emerged recently as tools for fighting drug-resistant planktonic bacteria and biofilms. In this review, we present the use of nanoparticles as active antimicrobial agents and drug delivery vehicles for antibacterial therapeutics. We further focus on how surface functionality of nanomaterials can be used to target both planktonic bacteria and biofilms.

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  • Authors: Kaoru Takahashi; Takashi Sako; Keitaro Fujita; Kozo Fujisue; +5 Authors
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    Authors: Sebastian Krogh;
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