Blood coagulation factor X exerts differential effects on adenovirus entry into human lymphocytes

It has been proposed that blood coagulation factors, principally factor X (FX), enhance the uptake of human adenovirus type 5 (Ad5) into cultured epithelial cells by bridging the viral hexon capsid protein and cell-surface heparan sulphate proteoglycans (HSPGs). We studied the effects of FX on Ad transduction of lymphoid cell lines (NK92MI, a natural killer cell line; Daudi, a B-cell line and Jurkat, a T-cell line) as well as primary peripheral blood lymphocytes (PBL) and HeLa epithelial cells using either replication-deficient Ad5, or a derivative in which the Ad5 fiber was replaced with that of another Ad type, Ad35, termed Ad5F35. PBL and NK92MI were resistant to Ad5 transduction. Transduction of Jurkat and Daudi cells by Ad5 was reduced by FX but without discernible effects on cell-surface Ad5 binding. FX reduced virus binding and transduction of all lymphoid cell lines by Ad5F35, as well as transduction of the T- and Natural Killer (NK)-cell populations of PBL. Flow cytometry analysis showed that all lymphoid cell lines were negative for HSPG components, in contrast to HeLa cells. FX reduced transduction of an HSPG-negative mutant Chinese hamster ovary cell line (CHOpgsA745) by Ad5 and Ad5F35, with Ad5F35 binding also being reduced by FX. These results point to fiber-dependent differences (Ad5 versus Ad35 fiber) in Ad binding to and transduction of human lymphoid and epithelial cells in the presence of FX

Modelling storm hydrodynamics on gravel beaches with XBeach-G

The research in this study was funded by the Engineering and Physical Sciences Research Council (EPSRC; EP/H040056/1). The full text is under embargo until 01.09.1

Observations of velocities, sand concentrations, and fluxes under velocity-asymmetric oscillatory flows

Peer reviewedPublisher PD

Role of Cellular Heparan Sulfate Proteoglycans in Infection of Human Adenovirus Serotype 3 and 35

Species B human adenoviruses (Ads) are increasingly associated with outbreaks of acute respiratory disease in U.S. military personnel and civil population. The initial interaction of Ads with cellular attachment receptors on host cells is via Ad fiber knob protein. Our previous studies showed that one species B Ad receptor is the complement receptor CD46 that is used by serotypes 11, 16, 21, 35, and 50 but not by serotypes 3, 7, and 14. In this study, we attempted to identify yet-unknown species B cellular receptors. For this purpose we used recombinant Ad3 and Ad35 fiber knobs in high-throughput receptor screening methods including mass spectrometry analysis and glycan arrays. Surprisingly, we found that the main interacting surface molecules of Ad3 fiber knob are cellular heparan sulfate proteoglycans (HSPGs). We subsequently found that HSPGs acted as low-affinity co-receptors for Ad3 but did not represent the main receptor of this serotype. Our study also revealed a new CD46-independent infection pathway of Ad35. This Ad35 infection mechanism is mediated by cellular HSPGs. The interaction of Ad35 with HSPGs is not via fiber knob, whereas Ad3 interacts with HSPGs via fiber knob. Both Ad3 and Ad35 interacted specifically with the sulfated regions within HSPGs that have also been implicated in binding physiologic ligands. In conclusion, our findings show that Ad3 and Ad35 directly utilize HSPGs as co-receptors for infection. Our data suggest that adenoviruses evolved to simulate the presence of physiologic HSPG ligands in order to increase infection

A Climate Index Optimized for Longshore Sediment Transport Reveals Interannual and Multidecadal Littoral Cell Rotations

A recent 35-year endpoint shoreline change analysis revealed significant counterclockwiserotations occurring in north-central Oregon, USA, littoral cells that extend 10s of kilometers in length.While the potential for severe El Niños to contribute to littoral cell rotations at seasonal to interannual scalewas previously recognized, the dynamics resulting in persistent (multidecadal) rotation were unknown,largely due to a lack of historical wave conditions extending back multiple decades and the difficulty ofseparating the timescales of shoreline variability in a high energy region. This study addresses this questionby (1) developing a statistical downscaling framework to characterize wave conditions relevant for longshoresediment transport during data-poor decades and (2) applying a one-line shoreline change model toquantitatively assess the potential for such large embayed beaches to rotate. A climateINdex was optimizedto capture variability in longshore wave power as a proxy for potentialLOngshore Sediment Transport(LOST_IN), and a procedure was developed to simulate many realizations of potential wave conditions fromthe index. Waves were transformed dynamically with Simulating Waves Nearshore to the nearshore asinputs to a one-line model that revealed shoreline rotations of embayed beaches at multiple time and spatialscales not previously discernible from infrequent observations. Model results indicate that littoral cellsrespond to both interannual and multidecadal oscillations, producing comparable shoreline excursions toextreme El Niño winters. The technique quantitatively relates morphodynamic forcing to specific climatepatterns and has the potential to better identify and quantify coastal variability on timescales relevant to achanging climate.This work would not have been possible without funding from the NSF Graduate Research Fellowship Program (GRFP) through NSF grant DGE-1314109, the Coastal and Ocean Climate Applications (COCA) program through NOAA grant NA15OAR4310243, NOAA’s Regional Integrated Sciences and Assessments Program (RISA), under NOAA grant NA15OAR4310145, and the Spanish Ministerio de Educación Cultura y Deporte FPU (Formación del Profesorado Universitario) studentship BOE-A-2013-12235. Beach survey data collection undertaken on the Oregon coast was made possible by the Northwest Association of Networked Ocean Observing Systems (NANOOS) through NOAA grant NA16NOS0120019

New energy geographies : a case study of yoga, meditation and healthfulness

Beginning with a routine day in the life of a practitioner of yoga and meditation and emphasising the importance of nurturing, maintaining and preventing the dissipation of diverse ‘energies’, this paper explores the possibilities for geographical health studies which take seriously ‘new energy geographies’. It is explained how this account is derived from in-depth fieldwork tracing how practitioners of yoga and meditation find times and spaces for these practices, often in the face of busy urban lifestyles. Attention is paid to the ‘energy talk’ featuring heavily in how practitioners describe the benefits that they perceive themselves to derive from these practices, and to claims made about ‘energies’ generated during the time-spaces of these practices which seemingly flow, usually with positive effects, into other domains of their lives. The paper then discusses the implications of this energy talk in the context of: (a) critically reviewing conventional approaches to studying ‘energy geographies’; (b) identifying an alertness to the likes of ‘affective energies’ surfacing in recent theoretically-attuned works of human geography (and cognate disciplines); and (c) exploring differing understandings of energy/energies extant in geographical studies of health and in step with the empirical research materials presented about yoga, meditation and healthfulness. While orientated towards explicitly geographical inquiries, the paper is intended as a statement of interest to the wider medical humanities

A new parameterisation for runup on gravel beaches

publisher: Elsevier articletitle: A new parameterisation for runup on gravel beaches journaltitle: Coastal Engineering articlelink: http://dx.doi.org/10.1016/j.coastaleng.2016.08.003 content_type: article copyright: © 2016 The Authors. Published by Elsevier B.V. Open Access funded by Engineering and Physical Sciences Research Counci

Wave farm impact on the beach profile: A case study

If wave energy is to become a fully-fledged renewable, its environmental impacts must be fully understood. The objective of the present work is to examine the impact of a wave farm on the beach profile through a case study. The methodology is based on two coupled numerical models: a nearshore wave propagation model and a morphodynamic model, which are run in two scenarios, both with and without the wave farm. Wave data from a nearby coastal buoy are used to prescribe the boundary conditions. A positive effect on the wave climate, the cross-shore sediment transport and, consequently, the evolution of the beach profile itself due to the presence of the wave farm was found. The wave farm leads to a reduction in the erosion of the beach face. This work constitutes the first stage of the investigation of the effectiveness of a wave farm as a coastal defence measure, and the accuracy of the quantification of the erosion reduction will be enhanced in future research. In any case, the overarching picture that emerges is that wave farms, in addition to providing carbon-free energy, can be used as elements of a coastal defence scheme.If wave energy is to become a fully-fledged renewable, its environmental impacts must be fully understood. The objective of the present work is to examine the impact of a wave farm on the beach profile through a case study. The methodology is based on two coupled numerical models: a nearshore wave propagation model and a morphodynamic model, which are run in two scenarios, both with and without the wave farm. Wave data from a nearby coastal buoy are used to prescribe the boundary conditions. A positive effect on the wave climate, the cross-shore sediment transport and, consequently, the evolution of the beach profile itself due to the presence of the wave farm was found. The wave farm leads to a reduction in the erosion of the beach face. This work constitutes the first stage of the investigation of the effectiveness of a wave farm as a coastal defence measure, and the accuracy of the quantification of the erosion reduction will be enhanced in future research. In any case, the overarching picture that emerges is that wave farms, in addition to providing carbon-free energy, can be used as elements of a coastal defence scheme

A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor

AbstractVirotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer

Adenovirus Gene Transfer to Amelogenesis Imperfecta Ameloblast-Like Cells

To explore gene therapy strategies for amelogenesis imperfecta (AI), a human ameloblast-like cell population was established from third molars of an AI-affected patient. These cells were characterized by expression of cytokeratin 14, major enamel proteins and alkaline phosphatase staining. Suboptimal transduction of the ameloblast-like cells by an adenovirus type 5 (Ad5) vector was consistent with lower levels of the coxsackie-and-adenovirus receptor (CAR) on those cells relative to CAR-positive A549 cells. To overcome CAR -deficiency, we evaluated capsid-modified Ad5 vectors with various genetic capsid modifications including “pK7” and/or “RGD” motif-containing short peptides incorporated in the capsid protein fiber as well as fiber chimera with the Ad serotype 3 (Ad3) fiber “knob” domain. All fiber modifications provided an augmented transduction of AI-ameloblasts, revealed following vector dose normalization in A549 cells with a superior effect (up to 404-fold) of pK7/RGD double modification. This robust infectivity enhancement occurred through vector binding to both αvβ3/αvβ5 integrins and heparan sulfate proteoglycans (HSPGs) highly expressed by AI-ameloblasts as revealed by gene transfer blocking experiments. This work thus not only pioneers establishment of human AI ameloblast-like cell population as a model for in vitro studies but also reveals an optimal infectivity-enhancement strategy for a potential Ad5 vector-mediated gene therapy for AI