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Len A.C.L.,University College LondonLondon | Starling S.,University College LondonLondon | Shivkumar M.,University College LondonLondon | Jolly C.,University College LondonLondon
Cell Reports | Year: 2017

HIV-1 spreads between CD4 T cells most efficiently through virus-induced cell-cell contacts. To test whether this process potentiates viral spread by activating signaling pathways, we developed an approach to analyze the phosphoproteome in infected and uninfected mixed-population T cells using differential metabolic labeling and mass spectrometry. We discovered HIV-1-induced activation of signaling networks during viral spread encompassing over 200 cellular proteins. Strikingly, pathways downstream of the T cell receptor were the most significantly activated, despite the absence of canonical antigen-dependent stimulation. The importance of this pathway was demonstrated by the depletion of proteins, and we show that HIV-1 Env-mediated cell-cell contact, the T cell receptor, and the Src kinase Lck were essential for signaling-dependent enhancement of viral dissemination. This study demonstrates that manipulation of signaling at immune cell contacts by HIV-1 is essential for promoting virus replication and defines a paradigm for antigen-independent T cell signaling. © 2017 The Author(s)


Cortese-Krott M.M.,Heinrich Heine University Düsseldorf | Kuhnle G.G.C.,University of Reading | Dyson A.,University College LondonLondon | Fernandez B.O.,University of Southampton | And 14 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Experimental evidence suggests that nitric oxide (NO) and hydrogen sulfide (H2S) signaling pathways are intimately intertwined, with mutual attenuation or potentiation of biological responses in the cardiovascular system and elsewhere. The chemical basis of this interaction is elusive. Moreover, polysulfides recently emerged as potential mediators of H2S/sulfide signaling, but their biosynthesis and relationship to NO remain enigmatic. We sought to characterize the nature, chemical biology, and bioactivity of key reaction products formed in the NO/sulfide system. At physiological pH, we find that NO and sulfide form a network of cascading chemical reactions that generate radical intermediates as well as anionic and uncharged solutes, with accumulation of three major products: nitrosopersulfide (SSNO-), polysulfides, and dinitrososulfite [N-nitrosohydroxylamine-N-sulfonate (SULFI/NO)], each with a distinct chemical biology and in vitro and in vivo bioactivity. SSNO- is resistant to thiols and cyanolysis, efficiently donates both sulfane sulfur and NO, and potently lowers blood pressure. Polysulfides are both intermediates and products of SSNO- synthesis/decomposition, and they also decrease blood pressure and enhance arterial compliance. SULFI/NO is a weak combined NO/nitroxyl donor that releases mainly N2O on decomposition; although it affects blood pressure only mildly, it markedly increases cardiac contractility, and formation of its precursor sulfite likely contributes to NO scavenging. Our results unveil an unexpectedly rich network of coupled chemical reactions between NO and H2S/sulfide, suggesting that the bioactivity of either transmitter is governed by concomitant formation of polysulfides and anionic S/N-hybrid species. This conceptual framework would seem to offer ample opportunities for the modulation of fundamental biological processes governed by redox switching and sulfur trafficking.


Deppisch F.F.,University College LondonLondon | Harz J.,University College LondonLondon | Huang W.-C.,University College LondonLondon | Hirsch M.,University of Valencia | Pas H.,TU Dortmund
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

Interactions that manifest themselves as lepton number violating processes at low energies in combination with sphaleron transitions typically erase any preexisting baryon asymmetry of the Universe. In this article, we discuss the constraints obtained from an observation of neutrinoless double beta decay in this context. If a new physics mechanism of neutrinoless double beta decay other than the standard light neutrino exchange is observed, typical scenarios of high-scale baryogenesis will be excluded unless the baryon asymmetry is stabilized via some new mechanism. We also sketch how this conclusion can be extended beyond the first lepton generation by incorporating lepton flavor violating processes. © 2015 American Physical Society.


Bocaege E.,French National Center for Scientific Research | Hillson S.,University College LondonLondon
American Journal of Physical Anthropology | Year: 2016

Objectives: The investigation of the record of growth locked in dental enamel provides a unique opportunity to build a comprehensive picture of growth disruption episodes during childhood. This study presents a new methodological basis for the analysis of enamel growth disruptions (enamel hypoplasia) using incremental microstructures of enamel. Methods: A three-dimensional technique based upon use of an Alicona 3D Infinite Focus imaging microscope and software is used to record developmental features in the enamel of human permanent mandibular lateral incisors of one individual from the Neolithic site of Çatalhöyük (Turkey). Using this new technique, perikymata are measured down the longitudinal axis of the crown from the incisal margin to the cervix and perikyma spacing profiles are constructed with this new technique. A mathematical basis for the detection of spacing anomalies, which serve as indicators of enamel hypoplasia is presented based upon these profiles. Results: Three clearly delineated defects were identified visually, then matched and confirmed metrically using the enamel surface and perikyma spacing profiles. Discussion: Human growth has often been used as an indicator of health in past societies because of developmental sensitivity to fluctuations in nutritional status and disease load. Hence, standardization of furrow-form defect identification is of crucial importance for reducing the amount of current subjectivity in the determination of a threshold for the identification of defects among individuals of past populations. The method presented here, which is based on microscopic images of the tooth crown as well as recorded measurements of incremental structures, represents a combined visual-metric approach using LOWESS residuals, and as such provides a substantial advancement to previous methods. It is therefore recommended that additional studies be carried out with this methodology to determine whether this method improves the reliability of enamel defect identification among individuals recovered from bioarchaeological contexts. © 2016 Wiley Periodicals, Inc.


McKemmish L.K.,University College LondonLondon | McKemmish L.K.,Australian National University | Gilbert A.T.B.,Australian National University
Journal of Chemical Theory and Computation | Year: 2015

Electron densities at nuclei are difficult to calculate accurately with all-Gaussian basis sets because they lack an electron-nuclear cusp. The newly developed mixed ramp-Gaussian basis sets, such as R-31G, possess electron-nuclear cusps due to the presence of ramp functions in the basis. The R-31G basis set is a general-purpose mixed ramp-Gaussian basis set modeled on the 6-31G basis set. The prediction of electron densities at nuclei using R-31G basis sets for Li-F outperforms Dunning, Pople, and Jensen general purpose all-Gaussian basis sets of triple-ζ quality or lower and the cc-pVQZ basis set. It is of similar quality to the specialized pcJ-0 basis set which was developed with partial decontraction of core functions and extra high exponent s-Gaussians to predict electron density at the nucleus. These results show significant advantages in the properties of mixed ramp-Gaussian basis sets compared to all-Gaussian basis sets. © 2015 American Chemical Society.


Arya C.,University College LondonLondon | Amiri A.,University College LondonLondon | Vassie P.,University College LondonLondon
Proceedings of the Institution of Civil Engineers: Structures and Buildings | Year: 2015

Civil infrastructure projects such as bridges can have a major impact on many of the issues relevant to sustainability and it is therefore important that civil and structural engineers have methods at their disposal that will help them deliver sustainable designs. This paper describes a new model for appraising the sustainability of bridges. The indictors used to assess sustainability are climate change, resource use, waste, biodiversity and heritage, noise, dust, vibration, aesthetics, employment and businesses, construction costs, maintenance costs and user delay costs. The paper describes the aim of each indicator and provides details of the methods of measurement. The paper also presents the results of a case study on the appraisal of three alternative designs of an over-bridge for a dual twolane motorway to discover which option is the most sustainable. Details of the key input parameters are provided. The way in which individual impacts are combined to produce an overall sustainability score for a given structure is highlighted. The paper concludes with a discussion on interpreting the results and ways of further improving the sustainability of the selected design. © ICE Publishing: All rights reserved.


Beard E.,University College LondonLondon | Brown J.,University College LondonLondon | McNeill A.,King's College | Michie S.,University College LondonLondon | West R.,University College LondonLondon
Thorax | Year: 2015

Background: The rise in electronic cigarette use by smokers may be responsible for the decreased use of licensed nicotine products and/or increased overall use of non-tobacco nicotine-containing products. This paper reports findings from the Smoking Toolkit Study (STS) tracking use of electronic cigarettes and licensed nicotine products to address this issue. Methods: Data were obtained from monthly surveys involving 14 502 cigarette smokers in England between March 2011 and November 2014. Smokers were asked about their use of electronic cigarettes and licensed nicotine products. Results: Prevalence of electronic cigarette use increased rapidly from 2.2% (95% CI 1.4% to 3.2%) in quarter 2 of 2011 to 20.8% (95% CI 18.3% to 23.4%) in quarter 3 of 2013, after which there was no change. Prevalence of licensed nicotine product use in smokers remained stable from quarter 2 of 2011 (17.4%, 95% CI 15.3% to 19.8%) to quarter 3 of 2013 (17.9%, 95% CI 15.62% to 20.5%), and thereafter declined steadily to 7.9% (95% CI 6.0% to 10.4%). Prevalence of use of any product was stable to quarter 1 of 2012, after which it increased from 18.5% (95% CI 16.3% to 21.0%) to 33.3% (95% CI 30.4% to 36.3%) in quarter 3 of 2013, and then decreased to 22.7% (95% CI 19.3% to 26.3%). Conclusions: The shapes of trajectories since 2011 suggest that electronic cigarettes are probably not responsible for the decline in use of licensed nicotine products. Electronic cigarettes appear to have increased the total market for use of non-tobacco nicotine-containing products.


Gentsch A.,University College LondonLondon | Panagiotopoulou E.,University College LondonLondon | Fotopoulou A.,University College LondonLondon
Current Biology | Year: 2015

Summary Social touch plays a powerful role in human life, with important physical and mental health benefits in development and adulthood. Touch is central in building the foundations of social interaction, attachment, and cognition [1-5], and early, social touch has unique, beneficial neurophysiological and epigenetic effects [6-9]. The recent discovery of a separate neurophysiological system for affectively laden touch in humans has further kindled scientific interest in the area [10, 11]. Remarkably, however, little is known about what motivates and sustains the human tendency to touch others in a pro-social manner. Given the importance of social touch, we hypothesized that active stroking elicits more sensory pleasure when touching others' skin than when touching one's own skin. In a set of six experiments (total N = 133) we found that healthy participants, mostly tested in pairs to account for any objective differences in skin softness, consistently judged another's skin as feeling softer and smoother than their own skin. We further found that this softness illusion appeared selectively when the touch activated a neurophysiological system for affective touch in the receiver. We conclude that this sensory illusion underlies a novel, bodily mechanism of socio-affective bonding and enhances our motivation to touch others. © 2015 The Authors.


Suttipong M.,University College LondonLondon | Striolo A.,University College LondonLondon
RSC Advances | Year: 2015

In our previous simulation study [J. Phys. Chem. C, 2011, 115, 17286], branched sodium dodecyl benzene-sulfonate (SDBS) surfactants showed self-assembled structures on single-walled carbon nanotubes (SWNTs) that were strongly dependent on tube diameter. Those results suggested that branched SDBS, as opposed to their linear counterparts, could specifically stabilize SWNTs of narrow diameter. Experimental data, however, show that SDBS stabilizes aqueous SWNTs of many diameters. This discrepancy between simulated and experimental results could be explained by the fact that experimental SDBS samples are isomeric mixtures. To test this possibility we report here molecular dynamics (MD) simulation results for equimolar mixtures of aqueous linear and branched SDBS on (6,6) and (20,20) SWNTs at ambient conditions. Our results suggest that there is no strong effect due to nanotube diameter on the morphology of mixed SDBS surfactant aggregates, although the adsorbed aggregate structure strongly depends on surfactant coverage. In-plane radial distribution functions suggest that linear and branched molecules distribute evenly onto the surfaces of (6,6) SWNTs, while some evidence of segregation, in which branched SDBS predominantly pack near other branched molecules, was obtained on (20,20) SWNTs at high surface coverage. These results suggest that the lack of specificity in stabilizing aqueous dispersions of carbon nanotubes using SDBS surfactants is probably due to the presence of multiple isomeric molecules in commercial surfactant samples. Perhaps more importantly, these simulations suggest that using mixtures of surfactants could affect the structure of the adsorbed aggregates, and the stability of aqueous dispersion of carbon nanotubes. © The Royal Society of Chemistry.


Freyja Olafsdottir H.,University College LondonLondon | Barry C.,University College LondonLondon | Saleem A.B.,University College LondonLondon | Hassabis D.,University College LondonLondon | Spiers H.J.,University College LondonLondon
eLife | Year: 2015

Dominant theories of hippocampal function propose that place cell representations are formed during an animal’s first encounter with a novel environment and are subsequently replayed during off-line states to support consolidation and future behaviour. Here we report that viewing the delivery of food to an unvisited portion of an environment leads to off-line pre-activation of place cells sequences corresponding to that space. Such ‘preplay’ was not observed for an unrewarded but otherwise similar portion of the environment. These results suggest that a hippocampal representation of a visible, yet unexplored environment can be formed if the environment is of motivational relevance to the animal. We hypothesise such goal-biased preplay may support preparation for future experiences in novel environments. © Ólafsdó ttir et al.

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