Broad host range plasmids can invade an unexpectedly diverse fraction of a soil bacterial community

Conjugal plasmids can provide microbes with full complements of new genes and constitute potent vehicles for horizontal gene transfer. Conjugal plasmid transfer is deemed responsible for the rapid spread of antibiotic resistance among microbes. While broad host range plasmids are known to transfer to diverse hosts in pure culture, the extent of their ability to transfer in the complex bacterial communities present in most habitats has not been comprehensively studied. Here, we isolated and characterized transconjugants with a degree of sensitivity not previously realized to investigate the transfer range of IncP- and IncPromA-type broad host range plasmids from three proteobacterial donors to a soil bacterial community. We identified transfer to many different recipients belonging to 11 different bacterial phyla. The prevalence of transconjugants belonging to diverse Gram-positive Firmicutes and Actinobacteria suggests that inter-Gram plasmid transfer of IncP-1 and IncPromA-type plasmids is a frequent phenomenon. While the plasmid receiving fractions of the community were both plasmid- and donor- dependent, we identified a core super-permissive fraction that could take up different plasmids from diverse donor strains. This fraction, comprising 80% of the identified transconjugants, thus has the potential to dominate IncP- and IncPromA-type plasmid transfer in soil. Our results demonstrate that these broad host range plasmids have a hitherto unrecognized potential to transfer readily to very diverse bacteria and can, therefore, directly connect large proportions of the soil bacterial gene pool. This finding reinforces the evolutionary and medical significances of these plasmids.Fil: Klumper, Uli. Technical University of Denmark; DinamarcaFil: Riber, Leise. Universidad de Copenhagen; DinamarcaFil: Dechesne, Arnaud. Technical University of Denmark; DinamarcaFil: Sannazzaro, Analía Inés. Universidad de Copenhagen; DinamarcaFil: Hansen, Lars H.. Universidad de Copenhagen; Dinamarca. Aarhus University. Roskilde; DinamarcaFil: Sørensen, Søren. Universidad de Copenhagen; DinamarcaFil: Smets, Barth F. Technical University of Denmark; Dinamarc

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Tuning fresh: radiation through rewiring of central metabolism in streamlined bacteria

Most free-living planktonic cells are streamlined and in spite of their limitations in functional flexibility, their vast populations have radiated into a wide range of aquatic habitats. Here we compared the metabolic potential of subgroups in the Alphaproteobacteria lineage SAR11 adapted to marine and freshwater habitats. Our results suggest that the successful leap from marine to freshwaters in SAR11 was accompanied by a loss of several carbon degradation pathways and a rewiring of the central metabolism. Examples for these are C1 and methylated compounds degradation pathways, the Entner–Doudouroff pathway, the glyoxylate shunt and anapleuretic carbon fixation being absent from the freshwater genomes. Evolutionary reconstructions further suggest that the metabolic modules making up these important freshwater metabolic traits were already present in the gene pool of ancestral marine SAR11 populations. The loss of the glyoxylate shunt had already occurred in the common ancestor of the freshwater subgroup and its closest marine relatives, suggesting that the adaptation to freshwater was a gradual process. Furthermore, our results indicate rapid evolution of TRAP transporters in the freshwater clade involved in the uptake of low molecular weight carboxylic acids. We propose that such gradual tuning of metabolic pathways and transporters toward locally available organic substrates is linked to the formation of subgroups within the SAR11 clade and that this process was critical for the freshwater clade to find and fix an adaptive phenotype.This work was supported by the Swedish Research Council (Grant Numbers 2012-4592 to AE and 2012-3892 to SB) and the Communiy Sequencing Programme of the US Department of Energy Joint Genome Institute. The work conducted by the US Department of Energy Joint Genome Institute, a DOE Office of Science User Facility, is supported under Contract No. DE-AC02-05CH11231

Analogue Transformations in Physics and their Application to Acoustics

Transformation optics has shaped up a revolutionary electromagnetic design paradigm, enabling scientists to build astonishing devices such as invisibility cloaks. Unfortunately, the application of transformation techniques to other branches of physics is often constrained by the structure of the field equations. We develop here a complete transformation method using the idea of analogue spacetimes. The method is general and could be considered as a new paradigm for controlling waves in different branches of physics, from acoustics in quantum fluids to graphene electronics. As an application, we derive an analogue transformation acoustics formalism that naturally allows the use of transformations mixing space and time or involving moving fluids, both of which were impossible with the standard approach. To demonstrate the power of our method, we give explicit designs of a dynamic compressor, a spacetime cloak for acoustic waves and a carpet cloak for a moving aircraft.This work was developed under the framework of the ARIADNA contract 4000104572/11/NL/KML of the European Space Agency. A. M. and J. S.-D. also acknowledge support from Consolider EMET project (CSD2008-00066), A. M. from project TEC2011-28664-C02-02, J.S.-D. from US Office of Naval Research, and C. B. and G. J. from the project FIS2008-06078-C03-01. We thank Reme Miralles for her help with Fig. 2.García Meca, C.; Carloni, S.; Barcelo, C.; Jannes, G.; Sánchez-Dehesa Moreno-Cid, J.; Martínez Abietar, AJ. (2013). Analogue Transformations in Physics and their Application to Acoustics. Scientific Reports. 3(2009):1-5. https://doi.org/10.1038/srep02009S1532009Pendry, J. B., Schurig, D. & Smith, D. R. Controlling electromagnetic fields. Science 312, 1780–1782 (2006).Leonhardt, U. Optical conformal mapping. Science 312, 1777–1780 (2006).Schurig, D. et al. Metamaterial Electromagnetic Cloak at Microwave Frequencies. Science 314, 977–980 (2006).Shalaev, V. M. Transforming Light. Science 322, 384–386 (2008).Greenleaf, A., Kurylev, Y., Lassas, M. & Uhlmann, G. Invisibility and inverse problems. B. Am. Math. Soc. 46, 55–97 (2009).Genov, D. A., Zhang, S. & Zhang, X. Mimicking celestial mechanics in metamaterials. Nat. Phys. 5, 687–692 (2009).Chen, H., Chan, C. T. & Sheng, P. Transformation optics and metamaterials. Nat. Mater. 9, 387–396 (2010).Leonhardt, U. & Philbin, T. Geometry and light. The science of invisibility (Dover Publications, 2010).Pendry, J. B., Aubry, A., Smith, D. R. & Maier, S. A. Transformation Optics and Subwavelength Control of Light. Science 337, 549 (2012).Post, E. G. Formal Structure of Electromagnetics: General Covariance and Electromagnetics (Interscience Publishers, New York, 1962).Cummer, S. A. & Schurig, D. One path to acoustic cloaking. New J. Phys. 9, 45 (2007).Chen, H. & Chan, C. T. Acoustic cloaking in three dimensions using acoustic metamaterials. Appl. Phys. Lett. 91, 183518 (2007).Norris, A. N. Acoustic metafluids. J. Acoust. Soc. Am. 125, 839 (2009).Chen, H. & Chan, C. T. Acoustic cloaking and transformation acoustics. J. Phys. D: Appl. Phys. 43, 113001 (2010).Zhang, S., Genov, D. A., Sun, C. & Zhang, X. Cloaking of Matter Waves. Phys. Rev. Lett. 100, 123002 (2008).McCall, M. W., Favaro, A., Kinsler, P. & Boardman, A. A spacetime cloak, or a history editor. J. Opt. 13, 024003 (2011).Fridman, M., Farsi, A., Okawachi, Y. & Gaeta, A. L. Demonstration of temporal cloaking. Nature 481, 62–65 (2012).Cummer, S. A. & Thompson, R. T. Frequency conversion by exploiting time in transformation optics. J. Opt. 13, 024007 (2011).Barceló, C., Liberati, S. & Visser, M. Analogue Gravity. Living Rev. Relativity 14, 3 (2011).Visser, M. Acoustic black holes: Horizons, ergospheres and Hawking radiation. Class. Quant. Grav. 15, 1767 (1998).Barceló, C. & Jannes, G. A Real Lorentz-FitzGerald contraction. Found. Phys. 38, 191 (2008).Bergmann, P. G. The Wave Equation in a Medium with a Variable Index of Refraction. J. Acoust. Soc. Am. 17, 329 (1946).Torrent, D., Håkansson, A., Cervera, F. & Sánchez-Dehesa, J. Homogenization of two-dimensional clusters of rigid rods in air. Phys. Rev. Lett. 96, 204302 (2006).Torrent, D. & Sánchez-Dehesa, J. Effective parameters of clusters of cylinders embedded in a nonviscous fluid or gas. Phys. Rev. B 74, 224305 (2006).Unruh, W. G. Experimental black hole evaporation? Phys. Rev. Lett. 46, 1351 (1981).Li, J. & Pendry, J. B. Hiding under the Carpet: A New Strategy for Cloaking. Phys. Rev. Lett. 101, 203901 (2008).Popa, B. I., Zigoneanu, L. & Cummer, S. A. Experimental acoustic ground cloak in air. Phys. Rev. Lett. 106, 253901 (2011).Garay, L. J., Anglin, J. R., Cirac, J. I. & Zoller, P. Black holes in Bose-Einstein condensates. Phys. Rev. Lett. 85, 4643 (2000).Lahav, O., Itah, A., Blumkin, A., Gordon, C. & Steinhauer, J. Realization of a sonic black hole analogue in a Bose-Einstein condensate. Phys. Rev. Lett. 105, 240401 (2010).Castro Neto, A. H., Guinea, F., Peres, N. M. R., Novoselov, K. S. & Geim, A. K. The electronic properties of graphene. Rev. Mod. Phys. 81, 109 (2009).Cortijo, A. & Vozmediano, M. A. H. Electronic properties of curved graphene sheets. Europhys. Lett. 77, 47002 (2007).Vakil, A. & Engheta, N. Transformation optics using graphene. Science 332, 1291 (2011)

Adhesive ligand tether length affects the size and length of focal adhesions and influences cell spreading and attachment.

Cells are known to respond to physical cues from their microenvironment such as matrix rigidity. Discrete adhesive ligands within flexible strands of fibronectin connect cell surface integrins to the broader extracellular matrix and are thought to mediate mechanosensing through the cytoskeleton-integrin-ECM linkage. We set out to determine if adhesive ligand tether length is another physical cue that cells can sense. Substrates were covalently modified with adhesive arginylglycylaspartic acid (RGD) ligands coupled with short (9.5 nm), medium (38.2 nm) and long (318 nm) length inert polyethylene glycol tethers. The size and length of focal adhesions of human foreskin fibroblasts gradually decreased from short to long tethers. Furthermore, we found cell adhesion varies in a linker length dependent manner with a remarkable 75% reduction in the density of cells on the surface and a 50% reduction in cell area between the shortest and longest linkers. We also report the interplay between RGD ligand concentration and tether length in determining cellular spread area. Our findings show that without varying substrate rigidity or ligand density, tether length alone can modulate cellular behaviour.This work was supported by the European Research Council to ADRH (grant agreement 282051). We wish to thank all CMBL members for help with this project

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Measurement of VH, H → b b ¯ production as a function of the vector-boson transverse momentum in 13 TeV pp collisions with the ATLAS detector

Cross-sections of associated production of a Higgs boson decaying into bottom-quark pairs and an electroweak gauge boson, W or Z, decaying into leptons are measured as a function of the gauge boson transverse momentum. The measurements are performed in kinematic fiducial volumes defined in the `simplified template cross-section' framework. The results are obtained using 79.8 fb-1 of proton-proton collisions recorded by the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13 TeV. All measurements are found to be in agreement with the Standard Model predictions, and limits are set on the parameters of an effective Lagrangian sensitive to modifications of the Higgs boson couplings to the electroweak gauge bosons

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference