Exploiting retrograde transport of Shiga-like toxin 1 for the delivery of exogenous antigens into the MHC class I presentation pathway

AbstractShiga-like toxin 1 (SLT) from Escherichia coli 0157:H7 enters mammalian cells by endocytosis from the cell surface to the endoplasmic reticulum before translocating into the cytosol. Here, SLT was engineered at its N- or C-terminus to carry a peptide derived from influenza virus Matrix protein for delivery to major histocompatibility complex (MHC) class I molecules. We show that SLT N-Ma was capable of sensitising cells for lysis by appropriate cytotoxic T-lymphocytes whilst no killing of SLT-resistant cells was observed. Our results demonstrate that peptide was liberated intracellularly and that retrograde transport of a disarmed cytotoxic protein can intersect the MHC class 1 presentation pathway

Understanding the role of contrasting urban contexts in healthy aging: an international cohort study using wearable sensor devices (the CURHA study protocol).

BACKGROUND: Given the challenges of aging populations, calls have been issued for more sustainable urban re-development and implementation of local solutions to address global environmental and healthy aging issues. However, few studies have considered older adults' daily mobility to better understand how local built and social environments may contribute to healthy aging. Meanwhile, wearable sensors and interactive map-based applications offer novel means for gathering information on people's mobility, levels of physical activity, or social network structure. Combining such data with classical questionnaires on well-being, physical activity, perceived environments and qualitative assessment of experience of places opens new opportunities to assess the complex interplay between individuals and environments. In line with current gaps and novel analytical capabilities, this research proposes an international research agenda to collect and analyse detailed data on daily mobility, social networks and health outcomes among older adults using interactive web-based questionnaires and wearable sensors. METHODS/DESIGN: Our study resorts to a battery of innovative data collection methods including use of a novel multisensor device for collection of location and physical activity, interactive map-based questionnaires on regular destinations and social networks, and qualitative assessment of experience of places. This rich data will allow advanced quantitative and qualitative analyses in the aim to disentangle the complex people-environment interactions linking urban local contexts to healthy aging, with a focus on active living, social networks and participation, and well-being. DISCUSSION: This project will generate evidence about what characteristics of urban environments relate to active mobility, social participation, and well-being, three important dimensions of healthy aging. It also sets the basis for an international research agenda on built environment and healthy aging based on a shared and comprehensive data collection protocol

GPS constraints on deformation in northern Central America from 1999 to 2017, Part 1 – Time-dependent modelling of large regional earthquakes and their post-seismic effects

We use continuous and campaign measurements from 215 GPS sites in northern Central America and southern Mexico to estimate coseismic and afterslip solutions for the 2009 Mw = 7.3 Swan Islands fault strike-slip earthquake and the 2012 Mw = 7.3 El Salvador and Mw = 7.4 Guatemala thrust-faulting earthquakes on the Middle America trench. Our simultaneous, time-dependent inversion of more than 350 000 daily GPS site positions gives the first jointly consistent estimates of the coseismic slips for all three earthquakes, their combined time-dependent post-seismic effects and secular station velocities corrected for both the coseismic and post-seismic deformation. Our geodetic slip solutions for all three earthquakes agree with previous estimates that were derived via static coseismic-offset modelling. Our time-dependent model, which attributes all transient post-seismic deformation to earthquake afterslip, fits nearly all of the continuous GPS site position time-series within their severalmillimetre position noise. Afterslip moments for the three earthquakes range from 35 to 140 per cent of the geodetic coseismic moments, with the largest afterslip estimated for the 2012 El Salvador earthquake along the weakly coupled El Salvador trench segment. Forward modelling of viscoelastic deformation triggered by all three earthquakes for a range of assumed mantle and lower crustal viscosities suggests that it accounts for under 20 per cent of the observed post-seismic deformation and possibly under 10 per cent

Hématologie /

2e éd.Bibliogr.: p. 419-423Index: p. 425-43

Femtosecond laser ablation ICP-MS measurement of otolith Sr:Ca and Ba:Ca composition reveal differential use of freshwater habitats for three amphidromous Sicyopterus (Teleostei: Gobioidei: Sicydiinae) species

cited By 17International audienceThe use of freshwater habitats was examined in three amphidromous goby species of the genus Sicyopterus using otolith microchemistry. Two species were endemic to either New Caledonia or Vanuatu whilst the other was widely distributed. Depositional patterns of strontium (Sr) and barium (Ba) in the otolith of adults were analysed with femtosecond laser ablation inductively coupled plasma mass spectrometry (ICP-MS). The Sr:Ca and Ba:Ca results uncovered three different adult behaviours within the freshwater habitat. Some fishes stayed in elevated locations (square profile); others undertook back-and-forth migrations between higher and lower reaches (up-and-down profile), and finally, others stayed in the lower reaches (constant profile). The consequences of these movements to larval survival or competition for food and territory are discussed. This work brings new knowledge on amphidromous behaviour, and it highlights the necessity of multi-elemental analysis to study amphidromy in freshwater systems. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles