Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end

Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process

A simple and robust method for connecting small-molecule drugs using gene-expression signatures

Interaction of a drug or chemical with a biological system can result in a gene-expression profile or signature characteristic of the event. Using a suitably robust algorithm these signatures can potentially be used to connect molecules with similar pharmacological or toxicological properties. The Connectivity Map was a novel concept and innovative tool first introduced by Lamb et al to connect small molecules, genes, and diseases using genomic signatures [Lamb et al (2006), Science 313, 1929-1935]. However, the Connectivity Map had some limitations, particularly there was no effective safeguard against false connections if the observed connections were considered on an individual-by-individual basis. Further when several connections to the same small-molecule compound were viewed as a set, the implicit null hypothesis tested was not the most relevant one for the discovery of real connections. Here we propose a simple and robust method for constructing the reference gene-expression profiles and a new connection scoring scheme, which importantly allows the valuation of statistical significance of all the connections observed. We tested the new method with the two example gene-signatures (HDAC inhibitors and Estrogens) used by Lamb et al and also a new gene signature of immunosuppressive drugs. Our testing with this new method shows that it achieves a higher level of specificity and sensitivity than the original method. For example, our method successfully identified raloxifene and tamoxifen as having significant anti-estrogen effects, while Lamb et al's Connectivity Map failed to identify these. With these properties our new method has potential use in drug development for the recognition of pharmacological and toxicological properties in new drug candidates.Comment: 8 pages, 2 figures, and 2 tables; supplementary data supplied as a ZIP fil

Patients’ use of information about medicine side effects in relation to experiences of suspected adverse drug reactions

Background Adverse drug reactions (ADRs) are common, and information about medicines is increasingly widely available to the public. However, relatively little work has explored how people use medicines information to help them assess symptoms that may be suspected ADRs. Objective Our objective was to determine how patients use patient information leaflets (PILs) or other medicines information sources and whether information use differs depending on experiences of suspected ADRs. Method This was a cross-sectional survey conducted in six National Health Service (NHS) hospitals in North West England involving medical in-patients taking at least two regular medicines prior to admission. The survey was administered via a questionnaire and covered use of the PIL and other medicines information sources, perceived knowledge about medicines risks/ADRs, experiences of suspected ADRs, plus demographic information. Results Of the 1,218 respondents to the survey, 18.8 % never read the PIL, whilst 6.5 % only do so if something unexpected happens. Educational level was related to perceived knowledge about medicines risks, but not to reading the PIL or seeking further information about medicines risks. Over half the respondents (56.0 %) never sought more information about possible side effects of medicines. A total of 57.2 % claimed they had experienced a suspected ADR. Of these 85.9 % were either very sure or fairly sure this was a reaction to a medicine. Over half of those experiencing a suspected ADR (53.8 %) had read the PIL, of whom 36.2 % did so before the suspected ADR occurred, the remainder afterwards. Reading the PIL helped 84.8 % of these respondents to decide they had experienced an ADR. Educational level, general knowledge of medicines risks and number of regular medicines used all increased the likelihood of experiencing an ADR. Conclusion More patients should be encouraged to read the PIL supplied with medicines. The results support the view that most patients feel knowledgeable about medicines risks and suspected ADRs and value information about side effects, but that reading about side effects in PILs or other medicines information sources does not lead to experiences of suspected ADRs

Detection of Massive Forming Galaxies at Redshifts Greater than One

The complex problem of when and how galaxies formed has not until recently been susceptible of direct attack. It has been known for some time that the excessive number of blue galaxies counted at faint magnitudes implies that a considerable fraction of the massive star formation in the universe occurred at z < 3, but, surprisingly, spectroscopic studies of galaxies down to a B magnitude of 24 found little sign of the expected high-z progenitors of current massive galaxies, but rather, in large part, small blue galaxies at modest redshifts z \sim 0.3. This unexpected population has diverted attention from the possibility that early massive star-forming galaxies might also be found in the faint blue excess. From KECK spectroscopic observations deep enough to encompass a large population of z > 1 field galaxies, we can now show directly that in fact these forming galaxies are present in substantial numbers at B \sim 24, and that the era from redshifts 1 to 2 was clearly a major period of galaxy formation. These z > 1 galaxies have very unusual morphologies as seen in deep HST WFPC2 images.Comment: 10 pages LaTeX + 5 PostScript figures in uuencoded gzipped tar file; aasms4.sty, flushrt.sty, overcite.sty (the two aastex4.0 and overcite.sty macros are available from xxx.lanl.gov) Also available (along with style files) via anonymous ftp to ftp://hubble.ifa.hawaii.edu/pub/preprints . E-print version of paper adds citation cross-references to other archived e-prints, where available. To appear in Nature October 19, 199

Soliton pair dynamics in patterned ferromagnetic ellipses

Confinement alters the energy landscape of nanoscale magnets, leading to the appearance of unusual magnetic states, such as vortices, for example. Many basic questions concerning dynamical and interaction effects remain unanswered, and nanomagnets are convenient model systems for studying these fundamental physical phenomena. A single vortex in restricted geometry, also known as a non-localized soliton, possesses a characteristic translational excitation mode that corresponds to spiral-like motion of the vortex core around its equilibrium position. Here, we investigate, by a microwave reflection technique, the dynamics of magnetic soliton pairs confined in lithographically defined, ferromagnetic Permalloy ellipses. Through a comparison with micromagnetic simulations, the observed strong resonances in the subgigahertz frequency range can be assigned to the translational modes of vortex pairs with parallel or antiparallel core polarizations. Vortex polarizations play a negligible role in the static interaction between two vortices, but their effect dominates the dynamics.Comment: supplemental movies on http://www.nature.com/nphys/journal/v1/n3/suppinfo/nphys173_S1.htm

Exceptional river gorge formation from unexceptional floods

An understanding of rates and mechanisms of incision and knickpoint retreat in bedrock rivers is fundamental to perceptions of landscape response to external drivers, yet only sparse field data are available. Here we present eye witness accounts and quantitative surveys of rapid, amphitheatre-headed gorge formation in unweathered granite from the overtopping of a rock-cut dam spillway by small-moderate floods (~100–1,500 m3 s−1). The amount of erosion demonstrates no relationship with flood magnitude or bedload availability. Instead, structural pattern of the bedrock through faults and joints appears to be the primary control on landscape change. These discontinuities facilitate rapid erosion (>270 m headward retreat; ~100 m incision; and ~160 m widening over 6 years) principally through fluvial plucking and block topple. The example demonstrates the potential for extremely rapid transient bedrock erosion even when rocks are mechanically strong and flood discharges are moderate. These observations are relevant to perceived models of gorge formation and knickpoint retreat

Selected reactive oxygen species and antioxidant enzymes in common bean after Pseudomonas syringae pv. phaseolicola and Botrytis cinerea infection

Phaseolus vulgaris cv. Korona plants were inoculated with the bacteria Pseudomonas syringae pv. phaseolicola (Psp), necrotrophic fungus Botrytis cinerea (Bc) or with both pathogens sequentially. The aim of the experiment was to determine how plants cope with multiple infection with pathogens having different attack strategy. Possible suppression of the non-specific infection with the necrotrophic fungus Bc by earlier Psp inoculation was examined. Concentration of reactive oxygen species (ROS), such as superoxide anion (O2 -) and H2O2 and activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) were determined 6, 12, 24 and 48 h after inoculation. The measurements were done for ROS cytosolic fraction and enzymatic cytosolic or apoplastic fraction. Infection with Psp caused significant increase in ROS levels since the beginning of experiment. Activity of the apoplastic enzymes also increased remarkably at the beginning of experiment in contrast to the cytosolic ones. Cytosolic SOD and guaiacol peroxidase (GPOD) activities achieved the maximum values 48 h after treatment. Additional forms of the examined enzymes after specific Psp infection were identified; however, they were not present after single Bc inoculation. Subsequent Bc infection resulted only in changes of H2O2 and SOD that occurred to be especially important during plant–pathogen interaction. Cultivar Korona of common bean is considered to be resistant to Psp and mobilises its system upon infection with these bacteria. We put forward a hypothesis that the extent of defence reaction was so great that subsequent infection did not trigger significant additional response

Accreting Neutron Stars in Low-Mass X-Ray Binary Systems

Using the Rossi X-ray Timing Explorer (RossiXTE), astronomers have discovered that disk-accreting neutron stars with weak magnetic fields produce three distinct types of high-frequency X-ray oscillations. These oscillations are powered by release of the binding energy of matter falling into the strong gravitational field of the star or by the sudden nuclear burning of matter that has accumulated in the outermost layers of the star. The frequencies of the oscillations reflect the orbital frequencies of gas deep in the gravitational field of the star and/or the spin frequency of the star. These oscillations can therefore be used to explore fundamental physics, such as strong-field gravity and the properties of matter under extreme conditions, and important astrophysical questions, such as the formation and evolution of millisecond pulsars. Observations using RossiXTE have shown that some two dozen neutron stars in low-mass X-ray binary systems have the spin rates and magnetic fields required to become millisecond radio-emitting pulsars when accretion ceases, but that few have spin rates above about 600 Hz. The properties of these stars show that the paucity of spin rates greater than 600 Hz is due in part to the magnetic braking component of the accretion torque and to the limited amount of angular momentum that can be accreted in such systems. Further study will show whether braking by gravitational radiation is also a factor. Analysis of the kilohertz oscillations has provided the first evidence for the existence of the innermost stable circular orbit around dense relativistic stars that is predicted by strong-field general relativity. It has also greatly narrowed the possible descriptions of ultradense matter.Comment: 22 pages, 7 figures, updated list of sources and references, to appear in "Short-period Binary Stars: Observation, Analyses, and Results", eds. E.F. Milone, D.A. Leahy, and D. Hobill (Dordrecht: Springer, http://www.springerlink.com

Quantum Acoustics with Surface Acoustic Waves

It has recently been demonstrated that surface acoustic waves (SAWs) can interact with superconducting qubits at the quantum level. SAW resonators in the GHz frequency range have also been found to have low loss at temperatures compatible with superconducting quantum circuits. These advances open up new possibilities to use the phonon degree of freedom to carry quantum information. In this paper, we give a description of the basic SAW components needed to develop quantum circuits, where propagating or localized SAW-phonons are used both to study basic physics and to manipulate quantum information. Using phonons instead of photons offers new possibilities which make these quantum acoustic circuits very interesting. We discuss general considerations for SAW experiments at the quantum level and describe experiments both with SAW resonators and with interaction between SAWs and a qubit. We also discuss several potential future developments.Comment: 14 pages, 12 figure

The stellar and sub-stellar IMF of simple and composite populations

The current knowledge on the stellar IMF is documented. It appears to become top-heavy when the star-formation rate density surpasses about 0.1Msun/(yr pc^3) on a pc scale and it may become increasingly bottom-heavy with increasing metallicity and in increasingly massive early-type galaxies. It declines quite steeply below about 0.07Msun with brown dwarfs (BDs) and very low mass stars having their own IMF. The most massive star of mass mmax formed in an embedded cluster with stellar mass Mecl correlates strongly with Mecl being a result of gravitation-driven but resource-limited growth and fragmentation induced starvation. There is no convincing evidence whatsoever that massive stars do form in isolation. Various methods of discretising a stellar population are introduced: optimal sampling leads to a mass distribution that perfectly represents the exact form of the desired IMF and the mmax-to-Mecl relation, while random sampling results in statistical variations of the shape of the IMF. The observed mmax-to-Mecl correlation and the small spread of IMF power-law indices together suggest that optimally sampling the IMF may be the more realistic description of star formation than random sampling from a universal IMF with a constant upper mass limit. Composite populations on galaxy scales, which are formed from many pc scale star formation events, need to be described by the integrated galactic IMF. This IGIMF varies systematically from top-light to top-heavy in dependence of galaxy type and star formation rate, with dramatic implications for theories of galaxy formation and evolution.Comment: 167 pages, 37 figures, 3 tables, published in Stellar Systems and Galactic Structure, Vol.5, Springer. This revised version is consistent with the published version and includes additional references and minor additions to the text as well as a recomputed Table 1. ISBN 978-90-481-8817-