Instability and front propagation in laser-tweezed lipid bilayer tubules

We study the mechanism of the `pearling' instability seen recently in experiments on lipid tubules under a local applied laser intensity. We argue that the correct boundary conditions are fixed chemical potentials, or surface tensions \Sigma, at the laser spot and the reservoir in contact with the tubule. We support this with a microscopic picture which includes the intensity profile of the laser beam, and show how this leads to a steady-state flow of lipid along the surface and gradients in the local lipid concentration and surface tension (or chemical potential). This leads to a natural explanation for front propagation and makes several predictions based on the tubule length. While most of the qualitative conclusions of previous studies remain the same, the `ramped' control parameter (surface tension) implies several new qualitative results. We also explore some of the consequences of front propagation into a noisy (due to pre-existing thermal fluctuations) unstable medium.Comment: 12 page latex + figures using epsf.sty to be published in Journal de Physique II, January 199

Budding and Domain Shape Transformations in Mixed Lipid Films and Bilayer Membranes

We study the stability and shapes of domains with spontaneous curvature in fluid films and membranes, embedded in a surrounding membrane with zero spontaneous curvature. These domains can result from the inclusion of an impurity in a fluid membrane, or from phase separation within the membrane. We show that for small but finite line and surface tensions and for finite spontaneous curvatures, an equilibrium phase of protruding circular domains is obtained at low impurity concentrations. At higher concentrations, we predict a transition from circular domains, or "caplets", to stripes. In both cases, we calculate the shapes of these domains within the Monge representation for the membrane shape. With increasing line tension, we show numerically that there is a budding transformation from stable protruding circular domains to spherical buds. We calculate the full phase diagram, and demonstrate a two triple points, of respectively bud-flat-caplet and flat-stripe-caplet coexistence.Comment: 14 pages, to appear in Phys Rev

Tectonic-sedimentary evolution of the northern margin of Gondwana during Late Palaeozoic – Early Cenozoic time in the Eastern Mediterranean region: evidence from the Central Taurus Mountains, Turkey.

The Taurus Mountains are an E-W trending mountain range in southern Turkey, with an elevation of up to 3500 m. In the south central Taurides, the Beysehir-Hoyran-Hadim nappes, a series of thrust sheets of Palaeozoic to Early Cenozoic age, are emplaced onto a relatively autochthonous Tauride platform, known as the Geyik Dag. These thrust sheets consist of a variety of discrete tectonostratigraphic units of continental platform, rifted margin and oceanic (ophiolitic) origin. It is generally accepted that the relatively autochthonous Tauride platform and the associated thrust sheets restore as a north-facing passive margin during Jurassic–Cretaceous time; however, the Triassic and earlier tectonic setting of the Tauride units is contentious. New data (mainly structural and sedimentological) presented here tests contrasting tectonic models of Late Palaeozoic – Early Mesozoic Tethys ocean evolution. Also, new light is shed on the Late Cretaceous and Early Cenozoic break-up and emplacement of the Tauride units during closure of Tethys. The Late Palaeozoic Tauride stratigraphy consists of shallow-marine carbonate, sandstone and mudstone, characteristic of a proximal passive margin. Detailed stratigraphic logging, facies interpretation, compositional analysis and geochemical evidence supports a passive margin setting, with sediment derived from the Tauride “basement”. Early – Middle Triassic mixed siliciclastic/carbonate sediments are interpreted as representing rifting and subsidence. Late Triassic coarser terrestrial clastics (Cayir Formation) are considered to represent a pulse of rift-related flexural uplift. Sediment provenance during this time was from the underlying Tauride platform to the north of the studied area. A previous hypothesis that a Palaeotethyan ocean closed in this area during latest Triassic “Cimmerian” orogenesis is discounted. Instead, structural and sedimentary data suggest that all of the deformation relates to Late Cretaceous – Early Cenozoic southward emplacement of the Beysehir-Hoyran-Hadim nappes. A first phase of thrusting (thin-skinned) emplaced ophiolite and distal margin units, whilst a second phase (thick-skinned) thrust platform lithologies southwards onto the foreland. Evidence is also summarised, notably from the Palaeozoic – Early Mesozoic Konya Complex to the north, which illustrates the relation of the Tauride platform to other geological terranes in Turkey and elsewhere in the Alpine-Himalayan orogenic belt. This thesis increases understanding of large-scale tectonic and sedimentary processes associated with continental margins and orogenic development

Enhanced effects of combined cognitive bias modification and computerised cognitive behaviour therapy on social anxiety

This study examines whether combined cognitive bias modification for interpretative biases (CBM-I) and computerised cognitive behaviour therapy (C-CBT) can produce enhanced positive effects on interpretation biases and social anxiety. Forty socially anxious students were randomly assigned into two conditions, an intervention group (positive CBM-I + C-CBT) or an active control (neutral CBM-I + C-CBT). At pre-test, participants completed measures of social anxiety, interpretative bias, cognitive distortions, and social and work adjustment. They were exposed to 6 × 30 min sessions of web-based interventions including three sessions of either positive or neutral CBM-I and three sessions of C-CBT, one session per day. At post-test and two-week follow-up, participants completed the baseline measures. A combined positive CBM-I + C-CBT produced less negative interpretations of ambiguous situations than neutral CBM-I + C-CBT. The results also showed that both positive CBM-I + C-CBT and neutral CBM-I + C-CBT reduced social anxiety and cognitive distortions as well as improving work and social adjustment. However, greater effect sizes were observed in the positive CBM-I + C-CBT condition than the control. This indicates that adding positive CBM-I to C-CBT enhanced the training effects on social anxiety, cognitive distortions, and social and work adjustment compared to the neutral CBM-I + C-CBT condition

In vitro biomarker discovery in the parasitic flatworm Fasciola hepatica for monitoring chemotherapeutic treatment

The parasitic flatworm Fasciola hepatica is a global food security risk. With no vaccines, the sustainability of triclabendazole (TCBZ) is threatened by emerging resistance. F. hepatica excretory/secretory (ES) products can be detected in host faeces and used to estimate TCBZ success and failure. However, there are no faecal based molecular diagnostics dedicated to assessing drug failure or resistance to TCBZ in the field. Utilising in vitro maintenance and sub-proteomic approaches two TCBZ stress ES protein response fingerprints were identified: markers of non-killing and lethal doses. This study provides candidate protein/peptide biomarkers to validate for detection of TCBZ failure and resistance

Instabilities and Oscillations in Isotropic Active Gels

We present a generic formulation of the continuum elasticity of an isotropic crosslinked active gel. The gel is described by a two-component model consisting of an elastic network coupled frictionally to a permeating fluid. Activity is induced by active crosslinkers that undergo an ATP-activated cycle and transmit forces to the network. The on/off dynamics of the active crosslinkers is described via rate equations for unbound and bound motors. For large activity motors yield a contractile instability of the network. At smaller values of activity, the on/off motor dynamics provides an effective inertial drag on the network that opposes elastic restoring forces, resulting in spontaneous oscillations. Our work provides a continuum formulation that unifies earlier microscopic models of oscillations in muscle sarcomeres and a generic framework for the description of the large scale properties of isotropic active solids.Comment: 13 pages, 5 figure

Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes

BACKGROUND: The phylum Platyhelminthes (flatworms) contains an important group of bilaterian organisms responsible for many debilitating and chronic infectious diseases of human and animal populations inhabiting the planet today. In addition to their biomedical and veterinary relevance, some platyhelminths are also frequently used models for understanding tissue regeneration and stem cell biology. Therefore, the molecular (genetic and epigenetic) characteristics that underlie trophic specialism, pathogenicity or developmental maturation are likely to be pivotal in our continued studies of this important metazoan group. Indeed, in contrast to earlier studies that failed to detect evidence of cytosine or adenine methylation in parasitic flatworm taxa, our laboratory has recently defined a critical role for cytosine methylation in Schistosoma mansoni oviposition, egg maturation and ovarian development. Thus, in order to identify whether this epigenetic modification features in other platyhelminth species or is a novelty of S. mansoni, we conducted a study simultaneously surveying for DNA methylation machinery components and DNA methylation marks throughout the phylum using both parasitic and non-parasitic representatives. RESULTS: Firstly, using both S. mansoni DNA methyltransferase 2 (SmDNMT2) and methyl-CpG binding domain protein (SmMBD) as query sequences, we illustrate that essential DNA methylation machinery components are well conserved throughout the phylum. Secondly, using both molecular (methylation specific amplification polymorphism, MSAP) and immunological (enzyme-linked immunoabsorbent assay, ELISA) methodologies, we demonstrate that representative species (Echinococcus multilocularis, Protopolystoma xenopodis, Schistosoma haematobium, Schistosoma japonicum, Fasciola hepatica and Polycelis nigra) within all four platyhelminth classes (Cestoda, Monogenea, Trematoda and ‘Turbellaria’) contain methylated cytosines within their genome compartments. CONCLUSIONS: Collectively, these findings provide the first direct evidence for a functionally conserved and enzymatically active DNA methylation system throughout the Platyhelminthes. Defining how this epigenetic feature shapes phenotypic diversity and development within the phylum represents an exciting new area of metazoan biology