The principles underlying the use of powder diffraction data in solving pharmaceutical crystal structures

Solving pharmaceutical crystal structures from powder diffraction data is discussed in terms of the methodologies that have been applied and the complexity of the structures that have been solved. The principles underlying these methodologies are summarized and representative examples of polymorph, solvate, salt and cocrystal structure solutions are provided, together with examples of some particularly challenging structure determinations.

Simple method for sub-diffraction resolution imaging of cellular structures on standard confocal microscopes by three-photon absorption of quantum dots

This study describes a simple technique that improves a recently developed 3D sub-diffraction imaging method based on three-photon absorption of commercially available quantum dots. The method combines imaging of biological samples via tri-exciton generation in quantum dots with deconvolution and spectral multiplexing, resulting in a novel approach for multi-color imaging of even thick biological samples at a 1.4 to 1.9-fold better spatial resolution. This approach is realized on a conventional confocal microscope equipped with standard continuous-wave lasers. We demonstrate the potential of multi-color tri-exciton imaging of quantum dots combined with deconvolution on viral vesicles in lentivirally transduced cells as well as intermediate filaments in three-dimensional clusters of mouse-derived neural stem cells (neurospheres) and dense microtubuli arrays in myotubes formed by stacks of differentiated C2C12 myoblasts.

IntFOLD: an integrated server for modelling protein structures and functions from amino acid sequences

IntFOLD is an independent web server that integrates our leading methods for structure and function prediction. The server provides a simple unified interface that aims to make complex protein modelling data more accessible to life scientists. The server web interface is designed to be intuitive and integrates a complex set of quantitative data, so that 3D modelling results can be viewed on a single page and interpreted by non-expert modellers at a glance. The only required input to the server is an amino acid sequence for the target protein. Here we describe major performance and user interface updates to the server, which comprises an integrated pipeline of methods for: tertiary structure prediction, global and local 3D model quality assessment, disorder prediction, structural domain prediction, function prediction and modelling of protein-ligand interactions. The server has been independently validated during numerous CASP (Critical Assessment of Techniques for Protein Structure Prediction) experiments, as well as being continuously evaluated by the CAMEO (Continuous Automated Model Evaluation) project. The IntFOLD server is available at: http://www.reading.ac.uk/bioinf/IntFOLD/

New insights on the role of paired membrane structures in coronavirus replication

The replication of coronaviruses, as in other positive-strand RNA viruses, is closely tied to the formation of membrane-bound replicative organelles inside infected cells. The proteins responsible for rearranging cellular membranes to form the organelles are conserved not just among the Coronaviridae family members, but across the order Nidovirales. Taken together, these observations suggest that the coronavirus replicative organelle plays an important role in viral replication, perhaps facilitating the production or protection of viral RNA. However, the exact nature of this role, and the specific contexts under which it is important have not been fully elucidated. Here, we collect and interpret the recent experimental evidence about the role and importance of membrane-bound organelles in coronavirus replication.

A novel plant-fungus symbiosis benefits the host without forming mycorrhizal structures

Most terrestrial plants form mutually beneficial symbioses with specific soil-borne fungi known as mycorrhiza. In a typical mycorrhizal association, fungal hyphae colonize plant roots, explore the soil beyond the rhizosphere and provide host plants with nutrients that might be chemically or physically inaccessible to root systems. Here, we combined nutritional, radioisotopic (33P) and genetic approaches to describe a plant growth promoting symbiosis between the basidiomycete fungus Austroboletus occidentalis and jarrah (Eucalyptus marginata), which has quite different characteristics. We show that the fungal partner does not colonize plant roots; hyphae are localized to the rhizosphere soil and vicinity and consequently do not transfer nutrients located beyond the rhizosphere. Transcript profiling of two high-affinity phosphate (Pi) transporter genes (EmPHT1;1 and EmPHT1;2) and hyphal-mediated 33Pi uptake suggest that the Pi uptake shifts from an epidermal to a hyphal pathway in ectomycorrhizal plants (Scleroderma sp.), similar to arbuscular mycorrhizal symbioses, whereas A. occidentalis benefits its host indirectly. The enhanced rhizosphere carboxylates are linked to growth and nutritional benefits in the novel symbiosis. This work is a starting point for detailed mechanistic studies on other basidiomycete–woody plant relationships, where a continuum between heterotrophic rhizosphere fungi and plant beneficial symbioses is likely to exist.

Investigation of high-efficiency Wireless Power Transfer criteria of resonantly-coupled loops and dipoles through analysis of the figure of merit

The efficiency of a Wireless Power Transfer (WPT) system is greatly dependent on both the geometry and operating frequency of the transmitting and receiving structures. By using Coupled Mode Theory (CMT), the figure of merit is calculated for resonantly-coupled loop and dipole systems. An in-depth analysis of the figure of merit is performed with respect to the key geometric parameters of the loops and dipoles, along with the resonant frequency, in order to identify the key relationships leading to high-efficiency WPT. For systems consisting of two identical single-turn loops, it is shown that the choice of both the loop radius and resonant frequency are essential in achieving high-efficiency WPT. For the dipole geometries studied, it is shown that the choice of length is largely irrelevant and that as a result of their capacitive nature, low-MHz frequency dipoles are able to produce significantly higher figures of merit than those of the loops considered. The results of the figure of merit analysis are used to propose and subsequently compare two mid-range loop and dipole WPT systems of equal size and operating frequency, where it is shown that the dipole system is able to achieve higher efficiencies than the loop system of the distance range examined.

Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich syndrome protein and ARP2/3 complex

The actin nodule is a novel F-actin structure present in platelets during early spreading. However, only limited detail is known regarding nodule organization and function. Here we use electron microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterize the structural organization and signalling pathways associated with nodule formation. Nodules are composed of up to four actin-rich structures linked together by actin bundles. They are enriched in the adhesion-related proteins talin and vinculin, have a central core of tyrosine phosphorylated proteins and are depleted of integrins at the plasma membrane. Nodule formation is dependent on Wiskott-Aldrich syndrome protein (WASp) and the ARP2/3 complex. WASp(-/-) mouse blood displays impaired platelet aggregate formation at arteriolar shear rates. We propose actin nodules are platelet podosome-related structures required for platelet-platelet interaction and their absence contributes to the bleeding diathesis of Wiskott-Aldrich syndrome.

Argument structures in Chinese university students’ argumentative writing: a contrastive study

Situated within a Systemic Functional Linguistics genre paradigm, this study adopted a function-based linguistic approach to examine the argument structures in English writing produced by Chinese university students of English as foreign language (EFL). Their English writing was contrasted with three other sets of argumentative essays in order to explore differences and similarities in the use of argument structures. The four sets of essays were produced by three groups of university students: native English- and Chinese-speaking university students and Chinese university EFL students. Participants’ interviews and questionnaire responses were also collected. The study found that most native English-speaking participants used an analytical arguing strategy, while most Chinese-speaking university participants preferred a hortatory argument structure both in their English and Chinese writing. It was also found that Chinese participants’ English writing was influenced by both English and Chinese.

Long-lived excited-state dynamics of i-motif structures probed by time-resolved infrared spectroscopy

UV-generated excited states of cytosine (C) nucleobases are precursors to mutagenic photoproduct formation. The i-motif formed from C-rich sequences is known to exhibit high yields of long-lived excited states following UV absorption. Here the excited states of several i-motif structures have been characterized following 267 nm laser excitation using time-resolved infrared spectroscopy (TRIR). All structures possess a long-lived excited state of ~300 ps and notably in some cases decays greater than 1 ns are observed. These unusually long-lived lifetimes are attributed to the interdigitated DNA structure which prevents direct base stacking overlap.

Reliability of orbital fits for resonant extrasolar planetary systems: the case of HD82943

We perform a statistical study of the process of orbital determination of the HD82943 extrasolar planetary system, using the current observational data set of N = 165 radial velocity (RV) measurements. Our aim is to analyse the dispersion of possible orbital fits leading to residuals compatible with the best solution, and to discuss the sensitivity of the results with respect to both the data set and the error distribution around the best fit. Although some orbital parameters (e.g. semimajor axis) appear well constrained, we show that the best fits for the HD82943 system are not robust, and at present it is not possible to estimate reliable solutions for these bodies. Finally, we discuss the possibility of a third planet, with a mass of 0.35M(Jup) and an orbital period of 900 d. Stability analysis and simulations of planetary migration indicate that such a hypothetical three-planet system could be locked in a double 2/1 mean-motion resonance, similar to the so-called Laplace resonance of the three inner Galilean satellites of Jupiter.

Suppression of small baryonic structures due to a primordial magnetic field

We investigate the impact of the existence of a primordial magnetic field on the filter mass, characterizing the minimum baryonic mass that can form in dark matter (DM) haloes. For masses below the filter mass, the baryon content of DM haloes are severely depressed. The filter mass is the mass when the baryon to DM mass ratio in a halo is equal to half the baryon to DM ratio of the Universe. The filter mass has previously been used in semi-analytic calculations of galaxy formation, without taking into account the possible existence of a primordial magnetic field. We examine here its effect on the filter mass. For homogeneous comoving primordial magnetic fields of B(0) similar to 1 or 2 nG and a re-ionization epoch that starts at a redshift z(s) = 11 and is completed at z(r) = 8, the filter mass is increased at redshift 8, for example, by factors of 4.1 and 19.8, respectively. The dependence of the filter mass on the parameters describing the re-ionization epoch is investigated. Our results are particularly important for the formation of low-mass galaxies in the presence of a homogeneous primordial magnetic field. For example, for B(0) similar to 1 nG and a re-ionization epoch of z(s) similar to 11 and z(r) similar to 7, our results indicate that galaxies of total mass M similar to 5 x 108 M(circle dot) need to form at redshifts z(F) greater than or similar to 2.0, and galaxies of total mass M similar to 108 M(circle dot) at redshifts z(F) greater than or similar to 7.7.

DETECTABILITY AND ERROR ESTIMATION IN ORBITAL FITS OF RESONANT EXTRASOLAR PLANETS

We estimate the conditions for detectability of two planets in a 2/1 mean-motion resonance from radial velocity data, as a function of their masses, number of observations and the signal-to-noise ratio. Even for a data set of the order of 100 observations and standard deviations of the order of a few meters per second, we find that Jovian-size resonant planets are difficult to detect if the masses of the planets differ by a factor larger than similar to 4. This is consistent with the present population of real exosystems in the 2/1 commensurability, most of which have resonant pairs with similar minimum masses, and could indicate that many other resonant systems exist, but are currently beyond the detectability limit. Furthermore, we analyze the error distribution in masses and orbital elements of orbital fits from synthetic data sets for resonant planets in the 2/1 commensurability. For various mass ratios and number of data points we find that the eccentricity of the outer planet is systematically overestimated, although the inner planet`s eccentricity suffers a much smaller effect. If the initial conditions correspond to small-amplitude oscillations around stable apsidal corotation resonances, the amplitudes estimated from the orbital fits are biased toward larger amplitudes, in accordance to results found in real resonant extrasolar systems.

HOMOLOGIES OF FLORAL STRUCTURES IN VELLOZIACEAE WITH PARTICULAR REFERENCE TO THE CORONA

New data on floral morphology, development, and vasculature in two Brazilian genera of the monocot family Velloziaceae (Pandanales) are used to explore the homologies of their unusual floral structures, especially the corona of Barbacenia and the corona-like appendages and multiple stamens of some Vellozia species. All Velloziaceae have epigynous flowers. Some species of Vellozia are polyandrous, and stamen number can be variable within species. In Vellozia jolyi, there is a single stamen opposite each sepal and a stamen fascicle (of three secondary stamens) opposite each petal. Each stamen possesses a single vascular bundle, and these are united into a single aggregate bundle in proximal regions of the fascicle. Stamens mature centripetally within each fascicle. The coronal appendages of both genera are closely associated with the stamens, but they share some vasculature with the tepals and develop late in ontogeny. The coronal organs cannot readily be homologized with any of the typical floral organs, but they show partial homology with both tepals and stamens. They are most readily interpreted as a late elaboration of the region between the petals and stamens associated with epigyny and the hypanthium.

Curiously composite structures of a retrotransposon and a complex repeat associated with chromosome ends of Rhynchosciara americana (Diptera: Sciaridae)

In Drosophila, telomere retrotransposons counterbalance the loss of telomeric DNA. The exceptional mechanism of telomere recovery characterized in Drosophila has not been found in lower dipterans (Nematocera). However, a retroelement resembling a telomere transposon and termed ""RaTART"" has been described in the nematoceran Rhynchosciara americana. In this work, DNA and protein sequence analyses, DNA cloning, and chromosomal localization of probes obtained either by PCR or by screening a genomic library were carried out in order to examine additional features of this retroelement. The analyses performed raise the possibility that RaTART represents a genomic clone composed of distinct repetitive elements, one of which is likely to be responsible for its apparent enrichment at chromosome ends. RaTART sequence in addition allowed to assess a novel subtelomeric region of R. americana chromosomes that was analyzed in this work after subcloning a DNA fragment from a phage insert. It contains a complex repeat that is located in the vicinity of simple and complex tandem repeats characterized previously. Quantification data suggest that the copy number of the repeat is significantly lower than that observed for the ribosomal DNA in the salivary gland of R. americana. A short insertion of the RaTART was identified in the cloned segment, which hybridized preferentially to subtelomeres. Like RaTART, it displays truncated sequences related to distinct retrotransposons, one of which has a conceptual translation product with significant identity with an endonuclease from a lepidopteran retrotransposon. The composite structure of this DNA stretch probably reflects mobile element activity in the subtelomeric region analyzed in this work.

Global analytic regularity for structures of co-rank one

We consider real analytic involutive structures V, of co-rank one, defined on a real analytic paracompact orientable manifold M. To each such structure we associate certain connected subsets of M which we call the level sets of V. We prove that analytic regularity propagates along them. With a further assumption on the level sets of V we characterize the global analytic hypoellipticity of a differential operator naturally associated to V. As an application we study a case of tube structures.