Skyrmion Multi-Walls

Skyrmion walls are topologically-nontrivial solutions of the Skyrme system which are periodic in two spatial directions. We report numerical investigations which show that solutions representing parallel multi-walls exist. The most stable configuration is that of the square $N$-wall, which in the $N\to\infty$ limit becomes the cubically-symmetric Skyrme crystal. There is also a solution resembling parallel hexagonal walls, but this is less stable.Comment: 7 pages, 1 figur

How Does the VSG Coat of Bloodstream Form African Trypanosomes Interact with External Proteins?

Variations on the statement "the variant surface glycoprotein (VSG) coat that covers the external face of the mammalian bloodstream form of Trypanosoma brucei acts a physical barrier" appear regularly in research articles and reviews. The concept of the impenetrable VSG coat is an attractive one, as it provides a clear model for understanding how a trypanosome population persists; each successive VSG protects the plasma membrane and is immunologically distinct from previous VSGs. What is the evidence that the VSG coat is an impenetrable barrier, and how do antibodies and other extracellular proteins interact with it? In this review, the nature of the extracellular surface of the bloodstream form trypanosome is described, and past experiments that investigated binding of antibodies and lectins to trypanosomes are analysed using knowledge of VSG sequence and structure that was unavailable when the experiments were performed. Epitopes for some VSG monoclonal antibodies are mapped as far as possible from previous experimental data, onto models of VSG structures. The binding of lectins to some, but not to other, VSGs is revisited with more recent knowledge of the location and nature of N-linked oligosaccharides. The conclusions are: (i) Much of the variation observed in earlier experiments can be explained by the identity of the individual VSGs. (ii) Much of an individual VSG is accessible to antibodies, and the barrier that prevents access to the cell surface is probably at the base of the VSG N-terminal domain, approximately 5 nm from the plasma membrane. This second conclusion highlights a gap in our understanding of how the VSG coat works, as several plasma membrane proteins with large extracellular domains are very unlikely to be hidden from host antibodies by VSG.The authors’ lab is funded by the Wellcome Trust (093008/Z10/Z) and the Medical Research Council (MR/L008246/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It was first available from PLOS via http://dx.doi.org/10.1371/journal.ppat.100525

Consultant medical trainers, modernising medical careers (MMC) and the European time directive (EWTD): tensions and challenges in a changing medical education context

Background: We analysed the learning and professional development narratives of Hospital Consultants training junior staff ('Consultant Trainers') in order to identify impediments to successful postgraduate medical training in the UK, in the context of Modernising Medical Careers (MMC) and the European Working Time Directive (EWTD). Methods: Qualitative study. Learning and continuing professional development (CPD), were discussed in the context of Consultant Trainers' personal biographies, organisational culture and medical education practices. We conducted life story interviews with 20 Hospital Consultants in six NHS Trusts in Wales in 2005. Results: Consultant Trainers felt that new working patterns resulting from the EWTD and MMC have changed the nature of medical education. Loss of continuity of care, reduced clinical exposure of medical trainees and loss of the popular apprenticeship model were seen as detrimental for the quality of medical training and patient care. Consultant Trainers' perceptions of medical education were embedded in a traditional medical education culture, which expected long hours' availability, personal sacrifices and learning without formal educational support and supervision. Over-reliance on apprenticeship in combination with lack of organisational support for Consultant Trainers' new responsibilities, resulting from the introduction of MMC, and lack of interest in pursuing training in teaching, supervision and assessment represent potentially significant barriers to progress. Conclusion: This study identifies issues with significant implications for the implementation of MMC within the context of EWTD. Postgraduate Deaneries, NHS Trusts and the new body; NHS: Medical Education England should deal with the deficiencies of MMC and challenges of ETWD and aspire to excellence. Further research is needed to investigate the views and educational practices of Consultant Medical Trainers and medical trainees

On the Strength of First Order Phase Transitions

Electroweak baryogenesis may solve one of the most fundamental questions we can ask about the universe, that of the origin of matter. It has become clear in the past few years that it also poses a multi-faceted challenge. In order to compute the tiny primordial baryonic excess, we probably must invoke physics beyond the standard model (an exciting prospect for most people), we must push perturbation theory to its ``limits'' (or beyond), and we must deal with nonequilibrium aspects of the phase transition. In this talk, I focus mainly on the latter issue, that of nonequilibrium aspects of first order transitions. In particular, I discuss the elusive question of ``weakness''. What does it mean to have a weak first order transition, and how can we distinguish between weak and strong? I argue that weak and strong transitions have very different dynamics; while strong transitions proceed by the usual bubble nucleation mechanism, weak transitions are characterized by a mixing of phases as the system reaches the critical temperature from above. I show that it is possible to clearly distinguish between the two, and discuss consequences for studies of first order transitions in general. (Invited talk given at the ``Electroweak Physics and the Early Universe'' workshop, Sintra, March 23-25, 1994.)Comment: 16 pages, 4 figures not included (can be obtained from hep-ph/9403310, or by request) RevTeX, DART-HEP-94/0

Cloning and Characterization of Maize miRNAs Involved in Responses to Nitrogen Deficiency

Although recent studies indicated that miRNAs regulate plant adaptive responses to nutrient deprivation, the functional significance of miRNAs in adaptive responses to nitrogen (N) limitation remains to be explored. To elucidate the molecular biology underlying N sensing/signaling in maize, we constructed four small RNA libraries and one degradome from maize seedlings exposed to N deficiency. We discovered a total of 99 absolutely new loci belonging to 47 miRNA families by small RNA deep sequencing and degradome sequencing, as well as 9 new loci were the paralogs of previously reported miR169, miR171, and miR398, significantly expanding the reported 150 high confidence genes within 26 miRNA families in maize. Bioinformatic and subsequent small RNA northern blot analysis identified eight miRNA families (five conserved and three newly identified) differentially expressed under the N-deficient condition. Predicted and degradome-validated targets of the newly identified miRNAs suggest their involvement in a broad range of cellular responses and metabolic processes. Because maize is not only an important crop but is also a genetic model for basic biological research, our research contributes to the understanding of the regulatory roles of miRNAs in plant adaption to N-deficiency stress

Evidence for a “Wattle and Daub” Model of the Cyst Wall of Entamoeba

The cyst wall of Entamoeba invadens (Ei), a model for the human pathogen Entamoeba histolytica, is composed of fibrils of chitin and three chitin-binding lectins called Jacob, Jessie3, and chitinase. Here we show chitin, which was detected with wheat germ agglutinin, is made in secretory vesicles prior to its deposition on the surface of encysting Ei. Jacob lectins, which have tandemly arrayed chitin-binding domains (CBDs), and chitinase, which has an N-terminal CBD, were each made early during encystation. These results are consistent with their hypothesized roles in cross-linking chitin fibrils (Jacob lectins) and remodeling the cyst wall (chitinase). Jessie3 lectins likely form the mortar or daub of the cyst wall, because 1) Jessie lectins were made late during encystation; 2) the addition to Jessie lectins to the cyst wall correlated with a marked decrease in the permeability of cysts to nucleic acid stains (DAPI) and actin-binding heptapeptide (phalloidin); and 3) recombinant Jessie lectins, expressed as a maltose-binding proteins in the periplasm of Escherichia coli, caused transformed bacteria to agglutinate in suspension and form a hard pellet that did not dissociate after centrifugation. Jessie3 appeared as linear forms and rosettes by negative staining of secreted recombinant proteins. These findings provide evidence for a “wattle and daub” model of the Entamoeba cyst wall, where the wattle or sticks (chitin fibrils likely cross-linked by Jacob lectins) is constructed prior to the addition of the mortar or daub (Jessie3 lectins)

Free energy of binding of coiled-coil complexes with different electrostatic environments: the influence of force field polarisation and capping

Coiled-coils are well known protein–protein interaction motifs, with the leucine zipper region of activator protein-1 (AP-1) consisting of the c-Jun and c-Fos proteins being a typical example. Molecular dynamics (MD) simulations using the MM/GBSA method have been used to predict the free energy of interaction of these proteins. The influence of force field polarisation and capping on the predicted free energy of binding of complexes with different electrostatic environments (net charge) were investigated. Although both force field polarisation and peptide capping are important for the prediction of the absolute free energy of binding, peptide capping has the largest influence on the predicted free energy of binding. Polarisable simulations appear better suited to determine structural properties of the complexes of these proteins while non-polarisable simulations seem to give better predictions of the associated free energies of bindin

Perceived spirituality, mindfulness and quality of life in psychiatric patients

There is some evidence of the relationship between spirituality and quality of life, but there are few bibliographic references on these constructs for patients suffering from mental illness; thus, this study was aimed at revealing the possible role of spiritual outlooks as a protective factor in these individuals. The sample consisted of 96 Portuguese psychiatric patients, selected from a psychiatric hospital and assessed based on parameters for quality of life, spirituality and mindfulness. The data support some theories about the nature of the spirituality. Spiritual beliefs are poorly correlated with the quality of life index, and there is a moderate association between these beliefs and some aspects of mindfulness. It is suggested that a spiritual outlook of psychiatric patients should be taken into account in psychological interventions