Hypertrophy of infected Peyer’s patches arises from global, interferon-receptor, and CD69-independent shutdown of lymphocyte egress

Lymphoid organ hypertrophy is a hallmark of localized infection. During the inflammatory response, massive changes in lymphocyte recirculation and turnover boost lymphoid organ cellularity. Intriguingly, the exact nature of these changes remains undefined to date. Here, we report that hypertrophy of Salmonella-infected Peyer's patches (PPs) ensues from a global "shutdown" of lymphocyte egress, which traps recirculating lymphocytes in PPs. Surprisingly, infection-induced lymphocyte sequestration did not require previously proposed mediators of lymphoid organ shutdown including type I interferon receptor and CD69. In contrast, following T-cell receptor-mediated priming, CD69 was essential to selectively block CD4+ effector T-cell egress. Our findings segregate two distinct lymphocyte sequestration mechanisms, which differentially rely on intrinsic modulation of lymphocyte egress capacity and inflammation-induced changes in the lymphoid organ environment.

Effect of short-wave (6-22 MHz) magnetic fields on sleep quality and melatonin cycle in humans: the Schwarzenburg shut-down study

This paper describes the results of a unique "natural experiment" of the operation and cessation of a broadcast transmitter with its short-wave electromagnetic fields (6-22 MHz) on sleep quality and melatonin cycle in a general human population sample. In 1998, 54 volunteers (21 men, 33 women) were followed for 1 week each before and after shut-down of the short-wave radio transmitter at Schwarzenburg (Switzerland). Salivary melatonin was sampled five times a day and total daily excretion and acrophase were estimated using complex cosinor analysis. Sleep quality was recorded daily using a visual analogue scale. Before shut down, self-rated sleep quality was reduced by 3.9 units (95% CI: 1.7-6.0) per mA/m increase in magnetic field exposure. The corresponding decrease in melatonin excretion was 10% (95% CI: -32 to 20%). After shutdown, sleep quality improved by 1.7 units (95% CI: 0.1-3.4) per mA/m decrease in magnetic field exposure. Melatonin excretion increased by 15% (95% CI: -3 to 36%) compared to baseline values suggesting a rebound effect. Stratified analyses showed an exposure effect on melatonin excretion in poor sleepers (26% increase; 95% CI: 8-47%) but not in good sleepers. Change in sleep quality and melatonin excretion was related to the extent of magnetic field reduction after the transmitter's shut down in poor but not good sleepers. However, blinding of exposure was not possible in this observational study and this may have affected the outcome measurements in a direct or indirect (psychological) way.

In vitro differentiation of near-unlimited numbers of functional mouse basophils using conditional Hoxb8

Background: Basophils constitute a rare leukocyte population known for their effector functions in inflammation and allergy, as well as more recently described immunoregulatory roles. Besides their low frequency, functional analysis of basophils is hindered by a short life span, inefficient ex vivo differentiation protocols, and lack of suitable cell models. A method to produce large quantities of basophils in vitro would facilitate basophil research and constitute a sought-after tool for diagnostic and drug testing purposes. Methods: A method is described to massively expand bone marrow–derived basophils in vitro. Myeloid progenitors are conditionally immortalized using Hoxb8 in the presence of interleukin-3 (IL-3) and outgrowing cell lines selected for their potential to differentiate into basophils upon shutdown of Hoxb8 expression. Results: IL-3-dependent, conditional Hoxb8-immortalized progenitor cell lines can be expanded and maintained in culture for prolonged periods. Upon shutdown of Hoxb8 expression, near-unlimited numbers of mature functional basophils can be differentiated in vitro within six days. The cells are end-differentiated and short-lived and express basophil-specific surface markers and proteases. Upon IgE- as well as C5a-mediated activation, differentiated basophils release granule enzymes and histamine and secrete Th2-type cytokines (IL-4, IL-13) and leukotriene C4. IL-3-deprivation induces apoptosis correlating with upregulation of the BH3-only proteins BCL-2-interacting mediator of cell death (BIM) and p53 upregulated modulator of apoptosis (PUMA) and downregulation of proviral integration site for Moloney murine leukemia virus 1 kinase (PIM-1). Conclusion: A novel method is presented to generate quantitative amounts of mouse basophils in vitro, which moreover allows genetic manipulation of conditionally immortalized progenitors. This approach may represent a useful alternative method to isolating primary basophils.

Stability of the Atlantic meridional overturning circulation: A model intercomparison.

The evolution of the Atlantic Meridional Overturning Circulation (MOC) in 30 models of varying complexity is examined under four distinct Representative Concentration Pathways. The models include 25 Atmosphere-Ocean General Circulation Models (AOGCMs) or Earth System Models (ESMs) that submitted simulations in support of the 5th phase of the Coupled Model Intercomparison Project (CMIP5) and 5 Earth System Models of Intermediate Complexity (EMICs). While none of the models incorporated the additional effects of ice sheet melting, they all projected very similar behaviour during the 21st century. Over this period the strength of MOC reduced by a best estimate of 22% (18%–25%; 5%–95% confidence limits) for RCP2.6, 26% (23%–30%) for RCP4.5, 29% (23%–35%) for RCP6.0 and 40% (36%–44%) for RCP8.5. Two of the models eventually realized a slow shutdown of the MOC under RCP8.5, although no model exhibited an abrupt change of the MOC. Through analysis of the freshwater flux across 30°–32°S into the Atlantic, it was found that 40% of the CMIP5 models were in a bistable regime of the MOC for the duration of their RCP integrations. The results support previous assessments that it is very unlikely that the MOC will undergo an abrupt change to an off state as a consequence of global warming.

SALSA: a tool to estimate the stray light contamination for low-Earth orbit observatories

Stray light contamination reduces considerably the precision of photometric of faint stars for low altitude spaceborne observatories. When measuring faint objects, the necessity of coping with stray light contamination arises in order to avoid systematic impacts on low signal-to-noise images. Stray light contamination can be represented by a flat offset in CCD data. Mitigation techniques begin by a comprehensive study during the design phase, followed by the use of target pointing optimisation and post-processing methods. We present a code that aims at simulating the stray-light contamination in low-Earth orbit coming from reflexion of solar light by the Earth. StrAy Light SimulAtor (SALSA) is a tool intended to be used at an early stage as a tool to evaluate the effective visible region in the sky and, therefore to optimise the observation sequence. SALSA can compute Earth stray light contamination for significant periods of time allowing missionwide parameters to be optimised (e.g. impose constraints on the point source transmission function (PST) and/or on the altitude of the satellite). It can also be used to study the behaviour of the stray light at different seasons or latitudes. Given the position of the satellite with respect to the Earth and the Sun, SALSA computes the stray light at the entrance of the telescope following a geometrical technique. After characterising the illuminated region of the Earth, the portion of illuminated Earth that affects the satellite is calculated. Then, the flux of reflected solar photons is evaluated at the entrance of the telescope. Using the PST of the instrument, the final stray light contamination at the detector is calculated. The analysis tools include time series analysis of the contamination, evaluation of the sky coverage and an objects visibility predictor. Effects of the South Atlantic Anomaly and of any shutdown periods of the instrument can be added. Several designs or mission concepts can be easily tested and compared. The code is not thought as a stand-alone mission designer. Its mandatory inputs are a time series describing the trajectory of the satellite and the characteristics of the instrument. This software suite has been applied to the design and analysis of CHEOPS (CHaracterizing ExOPlanet Satellite). This mission requires very high precision photometry to detect very shallow transits of exoplanets. Different altitudes and characteristics of the detector have been studied in order to find the best parameters, that reduce the effect of contamination. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

NA61/SHINE facility at the CERN SPS: beams and detector system

NA61/SHINE (SPS Heavy Ion and Neutrino Experiment) is a multi-purpose experimental facility to study hadron production in hadron-proton, hadron-nucleus and nucleus-nucleus collisions at the CERN Super Proton Synchrotron. It recorded the first physics data with hadron beams in 2009 and with ion beams (secondary 7Be beams) in 2011. NA61/SHINE has greatly profited from the long development of the CERN proton and ion sources and the accelerator chain as well as the H2 beamline of the CERN North Area. The latter has recently been modified to also serve as a fragment separator as needed to produce the Be beams for NA61/SHINE. Numerous components of the NA61/SHINE set-up were inherited from its predecessors, in particular, the last one, the NA49 experiment. Important new detectors and upgrades of the legacy equipment were introduced by the NA61/SHINE Collaboration. This paper describes the state of the NA61/SHINE facility — the beams and the detector system — before the CERN Long Shutdown I, which started in March 2013.

Multiple causes of the Younger Dryas cold period

The Younger Dryas cooling event disrupted the overall warming trend in the North Atlantic region during the last deglaciation. Climate change during the Younger Dryas was abrupt and thus provides insights into the sensitivity of the climate system to perturbations. The sudden Younger Dryas cooling has traditionally been attributed to a shutdown of the Atlantic Meridional Overturning Circulation by meltwater discharges. However, alternative explanations such as strong negative radiative forcing14 and a shift in atmospheric circulation have also been offered. Here we investigate the importance of these different forcings in coupled climate model experiments constrained by data assimilation. We find that the Younger Dryas climate signal as registered in proxy evidence is best simulated using a combination of processes: a weakened Atlantic Meridional Overturning Circulation, moderate negative radiative forcing and an altered atmospheric circulation. We conclude that none of the individual mechanisms alone provide a plausible explanation for the Younger Dryas cold period. We suggest that the triggers for abrupt climate changes such as the Younger Dryas are more complex than suggested so far, and that studies on the response of the climate system to perturbations should account for this complexity.