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Khufu’s Pyramid is one of the largest archaeological monuments in the world, and still contains unexplored voids. Here, the authors use cosmic-ray muon radiography in multiple positions to precisely characterize one of these inner structures called the North Face Corridor.

Binding of bacterial peptidoglycan muramyl dipeptides induces NOD2 activation and signalling via the downstream adaptor kinase RIP2. Here the authors show that RIP2 forms filaments via its CARD domain, analyse the structure of the CARD filaments and demonstrate the requirement of RIP2 polymerisation for the activation of NF-κB by NOD2.

Abstract This work aims at developing a diagnostic method based on Electron Paramagnetic Resonance (EPR) measurements of stable nitroxide radicals released from “EPR silent” liposomes. The liposome destabilisation and consequent radical release is enzymatically triggered by the action of phospholipase A2 (PLA2) present in the biological sample of interest. PLA2 are involved in a broad range of processes, and changes in their activity may be considered as a unique valuable biomarker for early diagnoses. The minimum amount of PLA2 measured “in vitro” was 0.09 U/mL. Moreover, the liposomes were successfully used to perform Overhauser-enhanced Magnetic Resonance Imaging (OMRI) in vitro at 0.2 T. The amount of radicals released by PLA2 driven liposome destabilization was sufficient to generate a well detectable contrast enhancement in the corresponding OMRI image.

Chlorophyll a concentration (Chl) is a key variable for estimating primary production (PP) through ocean-color remote sensing (OCRS). Accurate Chl estimates are crucial for better understanding of the spatio-temporal trends in PP in recent decades as a consequence of climate change. However, a number of studies have reported that currently operational chlorophyll a algorithms perform poorly in the Arctic Ocean (AO), largely due to the interference of colored and detrital material (CDM) with the phytoplankton signal in the visible part of the spectrum. To determine how and to what extent CDM biases the estimation of Chl, we evaluated the performances of eight currently available ocean-color algorithms: OC4v6, OC3Mv6, OC3V, OC4L, OC4P, AO.emp, GSM01 and AO.GSM. Our results suggest that the empirical AO.emp algorithm performs the best overall, but, for waters with high CDM acdm(443) > 0.067 m−1), a common scenario in the Arctic, the two semi-analytical GSM models yield better performance. In addition, sensitivity analyses using a spectrally and vertically resolved Arctic primary-production model show that errors in Chl mostly propagate proportionally to PP estimates, with amplification of up to 7%. We also demonstrate that, the higher level of CDM in relation to Chl in the water column, the larger the bias in both Chl and PP estimates. Lastly, although the AO.GSM is the best overall performer among the algorithms tested, it tends to fail for a significant number of pixels (16.2% according to the present study), particularly for waters with high CDM. Our results therefore suggest the ongoing need to develop an algorithm that provides reasonable Chl estimates for a wide range of optically complex Arctic waters.

Seasonal and inter-annual absorption properties of phytoplankton and non-algal particulate matter were studied in relation to phytoplankton biomass, as indexed by chlorophyll-a concentration, and presence of diatoms, as indexed by fucoxanthin concentration, using a 20-year time series of in situ data collected in the Northwest Atlantic. We found significant differences in the spatiotemporal variations of the bio-optical properties for three oceanic regimes: mesotrophic (Scotian Shelf), oligotrophic (Northwest Atlantic Basin, NAB), and subartic (Labrador Sea). The Scotian Shelf and NAB exhibited similar phenology with the spring and autumn blooms associated with low phytoplankton specific absorption, while only relatively high fucoxanthin concentration occurred in spring. The NAB showed a smaller seasonal variation than the Scotian Shelf in agreement with its oceanic conditions. The Labrador Sea showed a single phytoplankton bloom in spring followed by a continuous decrease in biomass the rest of the year. The relationship between phytoplankton absorption coefficient at 443 nm and chlorophyll-a concentration was consistent with other studies with coefficients that were region-dependent. Absorption by non-algal particulate matter remained between 5% and 60% of phytoplankton absorption with a mean of 15%. The slope of the non-algal particulate absorption varied with seasons and regions and appeared to depend on the trophic status with high values (i.e., up to 0.04) occurring during bloom conditions. We also introduced a new index, the phytoplankton apparent absorption wavelength (PAAW), a wavelength-weighted sum of absorption expressed in nanometers that provides information on the phytoplankton biomass and assemblage in a simple manner. Time series analysis of the PAAW revealed a decrease of this property in spring on the Scotian Shelf, NAB, and Labrador Sea and an increase in autumn on the Scotian Shelf and NAB, suggesting a shift in these ecosystems.

In this study, we present unique data collected with a Surface and Under-Ice Trawl (SUIT) during five campaigns between 2012 and 2017, covering the spring to summer and autumn transition in the Arctic Ocean, and the seasons of winter and summer in the Southern Ocean. The SUIT was equipped with a sensor array from which we retrieved: sea-ice thickness, the light field at the underside of sea ice, chlorophyll a concentration in the ice (in-ice chl a), and the salinity, temperature, and chl a concentration of the under-ice water. With an average trawl distance of about 2 km, and a global transect length of more than 117 km in both polar regions, the present work represents the first multi-seasonal habitat characterization based on kilometer-scale profiles. The present data highlight regional and seasonal patterns in sea-ice properties in the Polar Ocean. Light transmittance through Arctic sea ice reached almost 100% in summer, when the ice was thinner and melt ponds spread over the ice surface. However, the daily integrated amount of light under sea ice was maximum in spring. Compared to the Arctic, Antarctic sea-ice was thinner, snow depth was thicker, and sea-ice properties were more uniform between seasons. Light transmittance was low in winter with maximum transmittance of 73%. Despite thicker snow depth, the overall under-ice light was considerably higher during Antarctic summer than during Arctic summer. Spatial autocorrelation analysis shows that Arctic sea ice was characterized by larger floes compared to the Antarctic. In both Polar regions, the patch size of the transmittance followed the spatial variability of sea-ice thickness. In-ice chl a in the Arctic Ocean remained below 0.39 mg chl a m−2, whereas it exceeded 7 mg chl a m−2 during Antarctic winter, when water chl a concentrations remained below 1.5 mg chl a m−2, thus highlighting its potential as an important carbon source for overwintering organisms. The data analyzed in this study can improve large-scale physical and ecosystem models, habitat mapping studies and time series analyzed in the context of climate change effects and marine management.

Mucopolysaccharidoses are a class of lysosomal storage diseases, characterized by enzymatic deficiency in the degradation of specific glycosaminoglycans (GAG). Pathological accumulation of excess GAG leads to multiple clinical symptoms with systemic character, most severely affecting bones, muscles and connective tissues. Current therapies include periodic intravenous infusion of supplementary recombinant enzyme (Enzyme Replacement Therapy-ERT) or bone marrow transplantation. However, ERT has limited efficacy due to poor penetration in some organs and tissues. Here, we investigated the potential of the β-D-xyloside derivative odiparcil as an oral GAG clearance therapy for Maroteaux-Lamy syndrome (Mucopolysaccharidosis type VI, MPS VI). In vitro, in bovine aortic endothelial cells, odiparcil stimulated the secretion of sulphated GAG into culture media, mainly of chondroitin sulphate (CS) /dermatan sulphate (DS) type. Efficacy of odiparcil in reducing intracellular GAG content was investigated in skin fibroblasts from MPS VI patients where odiparcil was shown to reduce efficiently the accumulation of intracellular CS with an EC50 in the range of 1 μM. In vivo, in wild type rats, after oral administrations, odiparcil was well distributed, achieving μM concentrations in MPS VI disease-relevant tissues and organs (bone, cartilage, heart and cornea). In MPS VI Arylsulphatase B deficient mice (Arsb-), after chronic oral administration, odiparcil consistently stimulated the urinary excretion of sulphated GAG throughout the treatment period and significantly reduced tissue GAG accumulation in liver and kidney. Furthermore, odiparcil diminished the pathological cartilage thickening observed in trachea and femoral growth plates of MPS VI mice. The therapeutic efficacy of odiparcil was similar in models of early (treatment starting in juvenile, 4 weeks old mice) or established disease (treatment starting in adult, 3 months old mice). Our data demonstrate that odiparcil effectively diverts the synthesis of cellular glycosaminoglycans into secreted soluble species and this effect can be used for reducing cellular and tissue GAG accumulation in MPS VI models. Therefore, our data reveal the potential of odiparcil as an oral GAG clearance therapy for MPS VI patients.

The monitoring of Chlorophyll-a (Chl-a) concentration in high northern latitude waters has been receiving increased focus due to the rapid environmental changes in the sub-Arctic, Arctic. Spaceborne optical instruments allow the continuous monitoring of the occurrence, distribution, and amount of Chl-a. In recent years, the Ocean and Land Color Instruments (OLCI) onboard the Sentinel 3 (S3) A and B satellites were launched, which provide data about various aquatic environments on advantageous spatial, spectral, and temporal resolutions with high SNR. Although S3 OLCI could be favorable to monitor high northern latitude waters, there have been several challenges related to Chl-a concentration retrieval in these waters due to their unique optical properties coupled with challenging environments including high sun zenith angle, presence of sea ice, and frequent cloud covers. In this work, we aim to overcome these difficulties by developing a machine-learning (ML) approach designed to estimate Chl-a concentration from S3 OLCI data in high northern latitude optically complex waters. The ML model is optimized and requires only three S3 OLCI bands, reflecting the physical characteristic of Chl-a as input in the regression process to estimate Chl-a concentration with improved accuracy in terms of the bias (five times improvements.) The ML model was optimized on data from Arctic, coastal, and open waters, and showed promising performance. Finally, we present the performance of the optimized ML approach by computing Chl-a maps and corresponding certainty maps in highly complex sub-Arctic and Arctic waters. We show how these certainty maps can be used as a support to understand possible radiometric calibration issues in the retrieval of Level 2 reflectance over these waters. This can be a useful tool in identifying erroneous Level 2 Remote sensing reflectance due to possible failure of the atmospheric correction algorithm.

Magnetic resonance imaging can reveal exquisite anatomical details. However several diseases would benefit from an imaging technique able to specifically detect biochemical alterations. In this context protease activity imaging is one of the most promising areas of research.We designed an elastase substrate by grafting stable nitroxide free radicals on soluble elastin. This substrate generates a high Overhauser magnetic resonance imaging (OMRI) contrast upon digestion by the target proteases through the modulation of its rotational correlation time. The sensitivity is sufficient to generate contrasted images of the degranulation of neutrophils induced by a calcium ionophore from 2×10(4) cells per milliliter, well under the physiological neutrophils concentrations.These ex-vivo experiments give evidence that OMRI is suitable for imaging elastase activity from neutrophil degranulation. Provided that a fast protease-substrate is used these results open the door to better diagnoses of a number of important pathologies (cystic fibrosis, inflammation, pancreatitis) by OMRI or Electron Paramagnetic Resonance Imaging in vivo. It also provides a long-expected method to monitor anti-protease treatments efficiency and help pharmaceutical research.

Large rivers represent a significant component of inland waters and are considered sentinels and integrators of terrestrial and atmospheric processes. They represent hotspots for the transport and processing of organic and inorganic material from the surrounding landscape, which ultimately impacts the bio-optical properties and food webs of the rivers. In large rivers, hydraulic connectivity operates as a major forcing variable to structure the functioning of the riverscape, and--despite increasing interest in large-river studies--riverscape structural properties, such as the underwater spectral regime, and their impact on autotrophic ecological processes remain poorly studied. Here we used the St. Lawrence River to identify the mechanisms structuring the underwater spectral environment and their consequences on pico- and nanophytoplankton communities, which are good biological tracers of environmental changes. Our results, obtained from a 450 km sampling transect, demonstrate that tributaries exert a profound impact on the receiving river's photosynthetic potential. This occurs mainly through injection of chromophoric dissolved organic matter (CDOM) and non-algal material (tripton). CDOM and tripton in the water column selectively absorbed wavelengths in a gradient from blue to red, and the resulting underwater light climate was in turn a strong driver of the phytoplankton community structure (prokaryote/eukaryote relative and absolute abundances) at scales of many kilometers from the tributary confluence. Our results conclusively demonstrate the proximal impact of watershed properties on underwater spectral composition in a highly dynamic river environment characterized by unique structuring properties such as high directional connectivity, numerous sources and forms of carbon, and a rapidly varying hydrodynamic regime. We surmise that the underwater spectral composition represents a key integrating and structural property of large, heterogeneous river ecosystems and a promising tool to study autotrophic functional properties. It confirms the usefulness of using the riverscape approach to study large-river ecosystems and initiate comparison along latitudinal gradients.

BACKGROUND: Long-term adherence is a major issue in patients receiving home continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea-hypopnea syndrome (OSAHS). In a multicenter prospective cohort (the Institut de Recherche en Santé Respiratoire des Pays de la Loire [IRSR] sleep cohort) of consecutive OSAHS patients in whom CPAP had been prescribed for at least 90 days, we studied the impact on long-term treatment adherence of socioeconomic factors, patients and disease characteristics prior to CPAP initiation. METHODS AND PRINCIPAL FINDINGS: Among 1,141 patients in whom CPAP had been prescribed for an average of 504±251 days (range: 91 to 1035), 674 (59%) were adherent with a mean daily use of CPAP≥4 h (mean: 6.42±1.35 h). Stepwise regression analysis identified 4 independent factors of CPAP adherence including apnea-hypopnea index (AHI) (OR: 1.549, 95%CI 1.163 to 2.062 for AHI≥30 vs. AHI

Proteolysis, involved in many processes in living organisms, is tightly regulated in space and time under physiological conditions. However deregulation can occur with local persistent proteolytic activities, e.g. in inflammation, cystic fibrosis, tumors, or pancreatitis. Furthermore, little is known about the role of many proteases, hence there is a need of new imaging methods to visualize specifically normal or disease-related proteolysis in intact bodies.In this paper, a new concept for non invasive proteolysis imaging is proposed. Overhauser-enhanced Magnetic Resonance Imaging (OMRI) at 0.2 Tesla was used to monitor the enzymatic hydrolysis of a nitroxide-labeled protein. In vitro, image intensity switched from 1 to 25 upon proteolysis due to the associated decrease in the motional correlation time of the substrate. The OMRI experimental device used in this study is consistent with protease imaging in mice at 0.2 T without significant heating. Simulations show that this enzymatic-driven OMRI signal switch can be obtained at lower frequencies suitable for larger animals or humans.The method is highly sensitive and makes possible proteolysis imaging in three dimensions with a good spatial resolution. Any protease could be targeted specifically through the use of taylor-made cleavable macromolecules. At short term OMRI of proteolysis may be applied to basic research as well as to evaluate therapeutic treatments in small animal models of experimental diseases.