Genetic, structural, and molecular insights into the function of ras of complex proteins domains

Ras of complex proteins (ROC) domains were identified in 2003 as GTP binding modules in large multidomain proteins from Dictyostelium discoideum. Research into the function of these domains exploded with their identification in a number of proteins linked to human disease, including leucine-rich repeat kinase 2 (LRRK2) and death-associated protein kinase 1 (DAPK1) in Parkinson’s disease and cancer, respectively. This surge in research has resulted in a growing body of data revealing the role that ROC domains play in regulating protein function and signaling pathways. In this review, recent advances in the structural informa- tion available for proteins containing ROC domains, along with insights into enzymatic function and the integration of ROC domains as molecular switches in a cellular and organismal context, are explored.

Investigations into the formation and characterization of phospholipid microemulsions. IV. Pseudo-ternary phase diagrams of systems containing water-lecithin-alcohol and oil; The influence of oil

Phase studies have been performed for quaternary systems composed of egg lecithin, cosurfactant, water and oil. The lecithin used was the commercially available egg lecithin Ovothin 200 (which comprises ≥ 92% phosphatidylcholine). The cosurfactants employed were propanol and butanol, and these were used at lecithin/cosurfactant mixing ratios (Km) of 1:1 and 1.94:1 (weight basis). Six polar oils were investigated, including the alkanoic acids, octanoic and oleic, their corresponding ethyl esters and the medium and long chain triglycerides, Miglyol 812 and soybean oil. All oils, irrespective of the alcohol and the Km used, gave rise to systems that produced a stable isotropic region along the surfactant/oil axis (designated as a reverse microemulsion system). In addition, the systems incorporating propanol at both Km and butanol at a Km of 1.94: 1, generally gave rise to a liquid crystalline region and, in some cases, a second isotropic non-birefingent area (designated as a normal microemulsion system). The phase behaviour observed was largely dependent upon the alcohol and Km used and the size and the polarity of the oil present.

An investigation into the impact of using various techniques to estimate Arctic surface air temperature anomalies

Time series of global and regional mean Surface Air Temperature (SAT) anomalies are a common metric used to estimate recent climate change. Various techniques can be used to create these time series from meteorological station data. The degree of difference arising from using five different techniques, based on existing temperature anomaly dataset techniques, to estimate Arctic SAT anomalies over land and sea ice were investigated using reanalysis data as a testbed. Techniques which interpolated anomalies were found to result in smaller errors than non-interpolating techniques relative to the reanalysis reference. Kriging techniques provided the smallest errors in estimates of Arctic anomalies and Simple Kriging was often the best kriging method in this study, especially over sea ice. A linear interpolation technique had, on average, Root Mean Square Errors (RMSEs) up to 0.55 K larger than the two kriging techniques tested. Non-interpolating techniques provided the least representative anomaly estimates. Nonetheless, they serve as useful checks for confirming whether estimates from interpolating techniques are reasonable. The interaction of meteorological station coverage with estimation techniques between 1850 and 2011 was simulated using an ensemble dataset comprising repeated individual years (1979-2011). All techniques were found to have larger RMSEs for earlier station coverages. This supports calls for increased data sharing and data rescue, especially in sparsely observed regions such as the Arctic.

Samuel Beckett, the Gate Theatre Dublin, and the contemporary Irish independent theater sector: fragments of performance history

From 1991, when the Dublin Gate Theatre launched their Samuel Beckett Festival featuring nineteen of Beckett’s stage plays, to more recent years, the Gate dominated Irish productions of Beckett’s theater. The Gate Beckett Festival was remounted in 1996 at the Lincoln Center, New York, and at the Barbican Centre, London, in 1999, and individual or grouped productions have toured regularly since then in Ireland and internationally. However, since the Irish premiere of Waiting of Godot at the Pike Theatre in 1955, in addition to several Beckett plays mounted by the National Theatre, many independent Irish theater companies, such as Focus Theatre, Druid Theatre, and more recently Pan Pan Theatre, Blue Raincoat Theatre, The Corn Exchange, and Company SJ (under director Sarah Jane Scaife), have produced Beckett’s drama. While acknowledging earlier Irish productions, this essay will consider the role of the Dublin Gate Beckett Festival and the Beckett Centenary celebrations in Dublin in 2006 in greatly enhancing the marketability of Beckett’s work, and will discuss the proliferation of productions of Beckett’s stage plays (as opposed to stage adaptations of the prose work, which is a topic for another essay) in the independent theater sector in the Republic of Ireland since 2006. In addition to giving an overview of these recent productions, the essay will consider some issues at stake in creating or constructing performance histories

An investigation into the relationship between values and commitment: a study of staff in the UK charity sector

Abstract The concept of values “fit” has been a significant theme in the management literature for many years. It is argued that where there is alignment of staff and organizational values a range of positive outcomes are encountered. What is unclear is how this translates into the charity sector. This study explores the phenomenon of values alignment in two UK charities. Questionnaires were used to measure staff values, perceptions of organization values and staff commitment. Drawing on the work of Finegan (2000), an interaction term is used as a proxy for fit. Analyses of data from 286 participants indicated that it was the perceptions of organization values that had the greatest impact on staff commitment. The alignment of staff values and perceptions of organization values only had a degree of effect within one of the charities. This challenges the dominant view on such alignment and the implications of this are discussed. Keywords staff, values fit, commitment, organizational identification

Stakeholder interpretations of design: Semiotic insights into the briefing process

Briefing phase interactions between clients and designers are recognized as social engagements, characterized by communicative sign use, where conceptual ideas are gradually transformed into potential design solutions. A semiotic analysis of briefing communications between client stakeholders and designers provides evidence of the significance and importance of stakeholder interpretation and understanding of design, empirical data being drawn from a qualitative study of NHS hospital construction projects in the UK. It is contended that stakeholders engage with a project through communicative signs and artefacts of design, referencing personal cognitive knowledge in acts of interpretation that may be different from those of designers and externally appointed client advisers. Such interpretations occur in addition to NHS client and design team efforts to ‘engage’ with and ‘understand’ stakeholders using a variety of methods. Social semiotic theorizations indicate how narrative strategies motivate the formulation of signs and artefacts in briefing work, the role of sign authors and sign readers being elucidated as a result. Findings are contextualized against current understandings of briefing communications and stakeholder management practices, a more socially attuned understanding of briefing countering some of the process-led improvement models that have characterized much of the post-Egan report literature. A stakeholder interpretation model is presented as one potential method to safeguard against unforeseen interpretations occurring, the model aligning with the proposal for a more measured recognition of how designs can trigger interpretations among client stakeholders.

The influence of anisotropic F region ion velocity distributions on ionospheric ion outflows into the magnetosphere

The contribution to the field-aligned ionospheric ion momentum equation, due to coupling between pressure anisotropy and the inhomogeneous geomagnetic field, is investigated. We term this contribution the “hydrodynamic mirror force” and investigate its dependence on the ion drift and the resulting deformations of the ion velocity distribution function from an isotropic form. It is shown that this extra upforce increases rapidly with ion drift relative to the neutral gas but is not highly dependent on the ion-neutral collision model employed. An example of a burst of flow observed by EISCAT, thought to be the ionospheric signature of a flux transfer event at the magnetopause, is studied in detail and it is shown that the nonthermal plasma which results is subject to a hydrodynamic mirror force which is roughly 10% of the gravitational downforce. In addition, predictions by the coupled University College London-Sheffield University model of the ionosphere and thermosphere show that the hydrodynamic mirror force in the auroral oval is up to 3% of the gravitational force for Kp of about 3, rising to 10% following a sudden increase in cross-cap potential. The spatial distribution of the upforce shows peaks in the cusp region and in the post-midnight auroral oval, similar to that of observed low-energy heavy ion flows from the ionosphere into the magnetosphere. We suggest the hydrodynamic mirror force may modulate these outflows by controlling the supply of heavy ions to regions of ion acceleration and that future simulations of the effects of Joule heating on ion outflows should make allowance for it.

The modelled occurrence of non-thermal plasma in the ionospheric F-region and the possible consequences for ion outflows into the magnetosphere

A global, time-dependent, three-dimensional, coupled ionosphere-thermosphere model is used to predict the spatial distribution of non-thermal plasma in the F-layer. It is shown that, even for steady-state conditions with Kp as low as 3, the difference between the ion and neutral velocities often exceeds the neutral thermal speed by a factor, D', which can be as large as 4. Theoretically, highly non-Maxwellian, and probably toroidal, ion velocity distributions are expected when D' exceeds about 1.5. The lack of response of the neutral winds to sunward ion drifts in the dawn sector of the auroral oval cause this to be the region most likely to contain toroidal distributions. The maximum in D' is found in the throat region of the convection pattern, where the strong neutral winds of the afternoon sector meet the eastward ion flows of the morning sector. These predictions are of interest, not only to radar scientists searching for non-thermal ionospheric plasma, but also as one possible explanation of the initial heating and upward flows of ions in the cleft ion fountain and nightside auroral oval, both of which are a major source of plasma for the magnetosphere.

Low-energy ion flows into the magnetosphere

Ion flows from the ionosphere into the magnetosphere fall into two main categories: cold (<1eV), “classical” polar wind and heated (>1eV), suprathermal ion outflows. A wealth of new understanding of these outflows has resulted from the Dynamics Explorer Mission. This review describes both the confirmation of the predicted classical polar wind as well as the revelation of a great variety of low-energy suprathermal outflows: the cleft ion fountain, the nightside auroral fountaion (X-events, toroids and field-aligned flows) and polar cap outflows. The main emphasis is placed on flows at energies below about 50eV, observed by the Retarding Ion Mass Spectrometer (RIMS) on board the Dynamics Explorer 1 satellite; limited comparisons are made with results from other instruments which sample different energy ranges.

The geomagnetic mass spectrometer— mass and energy dispersions of ionospheric ion flows into the magnetosphere

NASA's Dynamics Explorer (DE) mission was designed to study the coupling between the Earth's magnetosphere, ionosphere and neutral thermosphere1. One area of major interest is the outflow of ionospheric plasma into the magnetosphere, the scale and significance of which is only now becoming apparent with the advent of mass-resolving, low-energy ion detectors. Here we compare observations of ion flows in the polar magnetosphere, made by the retarding ion mass spectrometer (RIMS)2 on DE1, with those made simultaneously in the topside ionosphere by the ion drift meter (IDM)3 on the lower-altitude DE2 spacecraft. The results show the dayside auroral ionosphere to be a significant and highly persistent source of plasma for the magnetosphere. The upwelling ionospheric ions are spatially dispersed, according to both their energy and mass, by the combined actions of the geomagnetic field and the dawn-to-dusk convection electric field, in an effect analogous to the operation of an ion mass spectrometer.

Innovative approaches For enhancing the flow of funds into the Benefit Sharing Fund of the International Treaty on Plant Genetic Resources for Food and Agriculture: an evaluation of options

This report assesses the implications and revenue-generating potential of options for reform of the International Treaty on Plant Genetic Resources for Food and Agriculture in the context of the structure of the global seed industry and the emerging landscape of plant variety innovation for different crops. The implementation of these options would require modifications of Treaty and provisions of the Standard Material Transfer Agreements to alter the nature of payment obligations related to different categories of products, the payment rates under different options and the coverage of crops in Annex-I to the Treaty.

New insights into the structure of exotic nuclei using the RISING active stopper

This conference paper outlines the operation and some of the preliminary physics results using the GSI RISING active stopper. Data are presented from an experiment using combined isomer and beta‐delayed gamma‐ray spectroscopy to study low‐lying spectral and decay properties of heavy‐neutron‐rich nuclei around A∼190 produced following the relativistic projectile fragmentation of 208Pb primary beam. The response of the RISING active stopper detector is demonstrated for both the implantation of heavy secondary fragments and in‐situ decay of beta‐particles. Beta‐delayed gamma‐ray spectroscopy following decays of the neutron‐rich nucleus 194Re is presented to demonstrate the experimental performance of the set‐up. The resulting information inferred from excited states in the W and Os daughter nuclei is compared with results from Skyrme Hartree‐Fock predictions of the evolution of nuclear shape.

Biomineralisation by earthworms: an investigation into the stability and distribution of amorphous calcium carbonate

Background Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis. Results The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg−1 (n = 3; ± std dev) per individual amino acid); the CaCO3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22–35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν2: ν4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA. Conclusions ACC present in earthworm CaCO3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components.

Regulation of cell migration in cancer: investigation into the regulation of cancer cell blebbing in the extracellular matrix

Cell migration is a highly coordinated process and any aberration in the regulatory mechanisms could result in pathological conditions such as cancer. The ability of cancer cells to disseminate to distant sites within the body has made it difficult to treat. Cancer cells also exhibit plasticity that makes them able to interconvert from an elongated, mesenchymal morphology to an amoeboid blebbing form under different physiological conditions. Blebs are spherical membrane protrusions formed by actomyosin-mediated contractility of cortical actin resulting in increased hydrostatic pressure and subsequent detachment of the membrane from the cortex. Tumour cells use blebbing as an alternative mode of migration by squeezing through preexisting gaps in the ECM, and bleb formation is believed to be mediated by the Rho-ROCK signaling pathway. However, the involvement of transmembrane water and ion channels in cell blebbing has not been examined. In the present study, the role of the transmembrane water channels, aquaporins, transmembrane ion transporters and lipid signaling enzymes in the regulation of blebbing was investigated. Using 3D matrigel matrix as an in vitro model to mimic normal extracellular matrix, and a combination of confocal and time-lapse microscopy, it was found that AQP1 knockdown by siRNA ablated blebbing of HT1080 and ACHN cells, and overexpression of AQP1-GFP not only significantly increased bleb size with a corresponding decrease in bleb numbers, but also induced bleb formation in non-blebbing cell lines. Importantly, AQP1 overexpression reduces bleb lifespan due to faster bleb retraction. This novel finding of AQP1-facilitated bleb retraction requires the activity of the Na+/H+ pump as inhibition of the ion transporter, which was found localized to intracellular vesicles, blocked bleb retraction in both cell lines. This study also demonstrated that a differential regulation of cell blebbing by AQP isoforms exists as knockdown of AQP5 had no effect on bleb formation. Data from this study also demonstrates that the lipid signaling PLD2 signals through PA in the LPA-LPAR-Rho-ROCK axis to positively regulate bleb formation in both cell lines. Taken together, this work provides a novel role of AQP1 and Na+/H+ pump in regulation of cell blebbing, and this could be exploited in the development of new therapy to treat cancer.