Glycosylphosphatidylinositols: More than just an anchor?

There is increasing interest in the role of glycosylphosphatidylinositol (GPI) anchors that attach some proteins to cell membranes. Far from being biologically inert, GPIs influence the targeting, intracellular trafficking and function of the attached protein. Our recent paper demonstrated the role of sialic acid on the GPI of the cellular prion protein (PrPC). The “prion diseases” arise following the conversion of PrPC to a disease-associated isoform called PrPSc or “prion”. Our paper showed that desialylated PrPC inhibited PrPSc formation. Aggregated PrPSc creates a signaling platform in the cell membrane incorporating and activating cytoplasmic phospholipase A2 (cPLA2), an enzyme that regulates PrPC trafficking and hence PrPSc formation. The presence of desialylated PrPC caused the dissociation of cPLA2 from PrP-containing platforms, reduced the activation of cPLA2 and inhibited PrPSc production. We concluded that sialic acid contained within the GPI attached to PrPC modifies local membrane microenvironments that are important in PrP-mediated cell signaling and PrPSc formation

Astrometric signatures of self-gravitating protoplanetary discs

We use high resolution numerical simulations to study whether gravitational instabilities within circumstellar discs can produce astrometrically detectable motion of the central star. For discs with masses of M_disc = 0.1 M_star, which are permanantly stable against fragmentation, we find that the magnitude of the astrometric signal depends upon the efficiency of disc cooling. Short cooling times produce prominent filamentary spiral structures in the disc, and lead to stellar motions that are potentially observable with future high precision astrometric experiments. For a disc that is marginally unstable within radii of \~10 au, we estimate astrometric displacements of 10-100 microarcsec on decade timescales for a star at a distance of 100 pc. The predicted displacement is suppressed by a factor of several in more stable discs in which the cooling time exceeds the local dynamical time by an order of magnitude. We find that the largest contribution comes from material in the outer regions of the disc and hence, in the most pessimistic scenario, the stellar motions caused by the disc could confuse astrometric searches for low mass planets orbiting at large radii. They are, however, unlikely to present any complications in searches for embedded planets orbiting at small radii, relative to the disc size, or Jupiter mass planets or greater orbiting at large radii.Comment: 6 pages, 9 figures, accepted for publication in MNRA

Proto-Brown Dwarf Disks as Products of Protostellar Disk Encounters

The formation of brown dwarfs via encounters between proto-stars has been confirmed with high-resolution numerical simulations with a restricted treatment of the thermal conditions. The new results indicate that young brown dwarfs (BDs) formed this way are disk-like and often reside in multiple systems. The newly-formed proto-BDs disks are up to 18 AU in size and spin rapidly making small-scale bipolar outflows, fragmentation and the possible formation of planetary companions likely as have recently been observed for BDs. The object masses range from 2 to 73 Jupiter masses, distributed in a manner consistent with the observed sub-stellar initial mass function. The simulations usually form multiple BDs on eccentric orbits about a star. One such system was hierarchical, a BD binary in orbit around a star, which may explain recently observed hierarchical systems. One third of the BDs were unbound after a few thousand years and interactions among orbiting BDs may eject more or add to the number of binaries. Improvements over prior work include resolution down to a Jupiter mass, self-consistent models of the vertical structure of the initial disks and careful attention to avoid artificial fragmentation.Comment: 4 pages, 3 figures, accepted for publication in ApJ Letter

Stellar Encounters with Massive Star-Disk Systems

The dense, clustered environment in which massive stars form can lead to interactions with neighboring stars. It has been hypothesized that collisions and mergers may contribute to the growth of the most massive stars. In this paper we extend the study of star-disk interactions to explore encounters between a massive protostar and a less massive cluster sibling using the publicly available SPH code GADGET-2. Collisions do not occur in the parameter space studied, but the end state of many encounters is an eccentric binary with a semi-major axis ~ 100 AU. Disk material is sometimes captured by the impactor. Most encounters result in disruption and destruction of the initial disk, and periodic torquing of the remnant disk. We consider the effect of the changing orientation of the disk on an accretion driven jet, and the evolution of the systems in the presence of on-going accretion from the parent core.Comment: 11 pages, 10 figures, accepted to Ap

Sialylated glycosylphosphatidylinositols suppress the production of toxic amyloid-ß oligomers

The production of amyloid-β (Aβ) is a key factor driving pathogenesis in Alzheimer's disease (AD). Increasing concentrations of soluble Aβ oligomers within the brain lead to synapse degeneration and the progressive dementia characteristic of AD. Since Aβ exists in both disease-relevant (toxic) and non-toxic forms, the factors that affected the release of toxic Aβ were studied in a cell model. 7PA2 cells expressing the human amyloid precursor protein released Aβ oligomers that caused synapse damage when incubated with cultured neurones. These Aβ oligomers had similar potency to soluble Aβ oligomers derived from the brains of Alzheimer's patients. Although the conditioned media from 7PA2 cells treated with the cellular prion protein (PrPC) contained Aβ, it did not cause synapse damage. The loss of toxicity was associated with a reduction in Aβ oligomers and an increase in Aβ monomers. The suppression of toxic Aβ release was dependent on the glycosylphosphatidylinositol (GPI) anchor attached to PrPC, and treatment of cells with specific GPIs alone reduced the production of toxic Aβ. The efficacy of GPIs was structure-dependent and the presence of sialic acid was critical. The conditioned medium from GPI-treated cells protected neurones against Aβ oligomer-induced synapse damage; neuroprotection was mediated by Aβ monomers. These studies support the hypothesis that the ratio of Aβ monomers to Aβ oligomers is a critical factor that regulates synapse damage

Substellar companions and isolated planetary mass objects from protostellar disc fragmentation

Self-gravitating protostellar discs are unstable to fragmentation if the gas can cool on a time scale that is short compared to the orbital period. We use a combination of hydrodynamic simulations and N-body orbit integrations to study the long term evolution of a fragmenting disc with an initial mass ratio to the star of M_disc/M_star = 0.1. For a disc which is initially unstable across a range of radii, a combination of collapse and subsequent accretion yields substellar objects with a spectrum of masses extending (for a Solar mass star) up to ~0.01 M_sun. Subsequent gravitational evolution ejects most of the lower mass objects within a few million years, leaving a small number of very massive planets or brown dwarfs in eccentric orbits at moderately small radii. Based on these results, systems such as HD 168443 -- in which the companions are close to or beyond the deuterium burning limit -- appear to be the best candidates to have formed via gravitational instability. If massive substellar companions originate from disc fragmentation, while lower-mass planetary companions originate from core accretion, the metallicity distribution of stars which host massive substellar companions at radii of ~1 au should differ from that of stars with lower mass planetary companions.Comment: 5 pages, accepted for publication in MNRA

Sociomaterial struggles at the frontline of strategy : a postphenomenological view of practice and power.

An important line of inquiry aligned with the ‘strategy as practice’ domain considers how strategy work is an exercise in power. Applying a lens influenced by—among others—Foucault, such work shows how actors shape their identities through and in relation to strategic discourses. Upper echelon managers discursively construct themselves as strategists, holding power over the subjectivities of those involved in implementing strategy. These discourses thus also work to shape the roles, identities and actions of these lower echelon actors to align with strategic intent. In turn, these same actors then construct their own identities in relation to these dominant discourses. Some studies build upon this position by attending to the role of technologies (e.g., accounting systems) in these flows of power, highlighting how such systems impose ways of working and thinking, and so define identities. However, such studies tend to dichotomise control and resistance, and tacitly view technology as an embodiment of pre-existing managerial intent. This under-emphasises the relational, co-productive nature of power and of technology’s role therein. This thesis aims to develop such an emphasis. I adopt a strong view of sociomateriality which sees the social and material as ontologically entangled. This is informed by Heideggerian conceptualisations, and also by ideas from ‘postphenomenology’, a school which further develops Heideggerian thought while also considering Foucauldian power in relation to technology use. Working with these ideas allows me to conceptualise human and technology as co-constitutive of (and within) the struggles that take shape as power flows through an organisation. Adopting this position, I examine ‘sociomaterial struggles’ in a study of frontline practitioners in a subsidiary company of a multinational health technology firm. Over 10-months, I collected their self-reported accounts of working with a new software suite as part of a ‘digital customer engagement strategy’. Analysing these accounts as ‘narratives of practices’, I show how the sense of self of each practitioner was first threatened and then (re)claimed through their individual, idiosyncratic relations with the technology—specifically, relations that set up struggles over subjectivities through a play of technology mediated objectivities, technology mediated intersubjectivities, and technology mediated subjectivities. Their stories weave together to reveal how the praxis that unfolded through these struggles shaped the local work of strategy. Overall, my thesis extends our understanding of how strategy is accomplished, attending to workers’ involvements with novel managerial ‘technologies of control’. It also contributes to theory, specifically to theorising power/resistance in strategy on the basis of a strong sociomaterial ontology