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The emergence of quantum technologies, including cold atom-based accelerometers, offers an opportunity to improve the performances of space geodesy missions. In this context, CNES initiated an assessment study called GRICE (GRadiométrie à Interféromètres quantiques Corrélés pour l’Espace) in order to evaluate the contribution of cold atom technologies to space geodesy and to the end users of geodetic data. In this paper, we present mission scenario for gravity field mapping based on a long baseline gradiometer. The mission is based on a constellation of two satellites, flying at an altitude of 373 km, each equipped with a cold atom accelerometer with a sensitivity of 6 × 10 - 10 m s - 2 τ - 1 / 2 . A laser link measures the distance between the two satellites and couples these two instruments in order to produce a correlated differential acceleration measurement. The main parameters, determining the performances of the payload, have been investigated. We carried out a general study of satellite architecture and simulations of the mission performances in terms of restitution of the gravity field. The simulations show that this concept would give its best performance in terms of monthly gravity fields recovery under 1000 km resolution. In the resolution band between 1000 and 222 km, the improvement of the GRICE gradient approach over the traditional range-rate approach is globally in the order of 10 to 25%.

IDEFIX, a rover to be delivered to the martian moon Phobos, is part of the Martian Moons eXploration (MMX) mission by the Japan Aerospace Exploration Agency, JAXA. MMX will explore both moons of Mars remotely but will also land on Phobos and collect samples from its surface and return them back to Earth. The IDEFIX rover will be released from the main spacecraft during its landing rehearsal at an altitude of about 40 m. It will fall to the surface, probably bounce several times and upright itself after having come to rest by applying an autonomous sequence of the deployment of its locomotion system. This sequence is followed by deployment of the solar generator and recharging of the batteries. After commissioning, on-Phobos operations are planned for at least 100 (Earth-) days. Sequences of science operations (instrument measurements), driving, battery charging and communications with Earth (via the main spacecraft) will alternate in a way to maximize scientific return and fulfill technical demonstration goals. IDEFIX accommodates a payload of four scientific instruments: a Raman spectrometer (RAX), a stereo pair of cameras looking forwards (NavCams; also used for navigation), a radiometer (miniRAD), and two cameras looking at the wheel-surface interface (WheelCams). MMX will be launched in autumn 2026, the Rover delivery to Phobos is currently planned for late 2028, before the first touch down of the spacecraft and sample collection. The Rover is a contribution by the Centre National d’Etudes Spatiales (CNES) and the German Aerospace Center (DLR) with additional contributions from INTA (Spain) and JAXA (Japan).

Two proteins of 17 and 24 kDa, respectively, which were immunologically related to bikunin, were purified from urine of healthy men, using in the last step a trypsin CNBr-sepharose affinity column. These proteins strongly inhibited calcium oxalate (CaOx) crystallization in two in vitro models. In the first model, the presence of 8 microg/ml protein in a medium containing 0.76 mM CaCl2 (with 45Ca) and 0.76 mM ammonium oxalate inhibited the crystallization process by 80%, as estimated by supernatant radioactivity after 60 min of incubation. A similar inhibition was observed in the second turbidimetric model, where the CaOx crystallization kinetics were followed for 10 min at 620 nm in a medium containing 4 mM CaCl2 and 0.5 mM Na2Ox. These proteins were used as standard protein for the development of an enzyme-linked immunosorbent assay (ELISA) in urine. Mean (+/-SEM) urinary bikunin concentration in 18 healthy subjects was 5.01 +/- 0.91 microg/ml. This was a concentration range of strong inhibitory activity in vitro. Bikunin values were nearly 50% lower (2.54 +/- 0.42 microg/ml, P=0.007) in 31 CaOx renal stone formers (having weddelite crystals in their first morning urine) than in the healthy volunteers. A correlation was found between urinary bikunin and alpha-1 microglobulin concentrations in the control group (y=0.73x + 1.09, r2=0.8) while no such correlation existed in the lithiasis group. In conclusion, bikunin exerts a strong inhibitory action of CaOx crystallization in vitro. Its involvement in urinary CaOx crystallization of stone formers is highly probable, based on the significant decrease in its urinary concentration in the majority of stone formers studied.

In the past few years, alpha-1-microglobulin (alpha1m) has been copurified from human urine with bikunin, a potent inhibitor of calcium oxalate (CaOx) crystallization in vitro. In this study, we have purified alpha1m without bikunin contamination and investigated its possible role in CaOx crystallization by in vitro and in vivo studies. Alpha-1m was purified with an anti-alpha1m antibodies CNBr-activated sepharose column. Two molecular species of alpha1m of respectively 30 and 60 kDa were purified. For each protein, two blots of 30 and 60 kDa cross-reacted with anti-alpha1m antibodies, suggesting that these two forms were derived one from the other. Both protein species inhibited CaOx crystallization in a dose-dependent manner in two in vitro tests. In the first test, the presence of alpha1m of 30 kDa (8 microg/ml) in a medium containing 0. 76 mM CaCl(2) (with (45)Ca) and 0.76 mM Ox(NH(4))(2) inhibited CaOx crystallization by 38% as estimated by supernatant radioactivity after 1 h of agitation. In the second test, CaOx kinetics were examined for 3 to 10 min in a turbidimetric model at 620 nm. The presence of alpha1m of 30 kDa in a medium containing 4 mM CaCl(2) and 0.5 mM Na(2)Ox inhibited CaOx crystallization by 41.5%, as estimated by the slope modification of turbidimetric curve. Alpha-1m can be considered as another inhibitor of urinary CaOx crystal formation, as shown by the present in vitro studies. Using an ELISA assay, we found that urinary alpha1m concentration was significantly lower in 31 CaOx stone formers than in 18 healthy subjects (2.95 +/- 0.29 vs 5.34 +/- 1.08 mg/l respectively, P = 0.01). The decreased concentration of alpha1m in CaOx stone formers could be responsible in these patients, at least in part, for an increased risk of CaOx crystalluria.

Twenty male Wistar rats, weighing 150 g, were placed in metabolic cages on a 30% sucrose diet for 7 days, before allocation to two groups: a control group (n = 5) and a lactose group (n = 15). They received respectively a 30% sucrose diet or a 30% lactose diet for 8 weeks, each containing 0.67% calcium and 0.38% phosphorus. After 4 (T1) and 8 (T2) weeks, the serum calcium (Ca) and citrate levels were significantly (P < 0.01) higher in rats fed the lactose diet. Serum alkaline phosphatase activity was increased in the lactose group (P < 0.01) at T1 and T2. The lactose-rich diet induced an increase in urinary Ca excretion at T1 and T2; citrate excretion was only enhanced at T2 (P < 0.001). No difference between the two groups was observed in urinary oxalate (Ox) excretion or creatinine clearance. Crystalluria analysis revealed a marked number (>300/mm3 at T1 and T2) of calcium oxalate dihydrate crystals (COD) in rats fed the lactose-rich diet, whereas no COD crystals were observed in sucrose-fed control rats at any time point. The formation of COD crystals in lactose-fed rats was related to an increase in calcium oxalate (CaOx) product (pCaOx), which was respectively 12.6 vs 3.9 at T1 and 10.5 vs 1.8 at T2, and an increase in CaOx ratio (Ca/Ox), which was 99.1 vs 7.5 and 67.5 vs 18.5 at T1 and T2, respectively. The high pCaOx and Ca/Ox ratios in the lactose group were due to hypercalciuria, in agreement with the number and the type of crystals. The present experimental model confirms that the ingestion of a 30% lactose diet increases urinary Ca excretion without changing urinary Ox excretion and shows for the first time that it induces a stable and marked crystalluria composed of COD. Such a non-nephrotoxic and stable model is of interest for the study of CaOx crystal formation secondary to hypercalciuria, and thus afterwards eventually for CaOx nephrolithiasis.

The emergence of quantum technologies, including cold atom based accelerometers, offers an opportunity to improve the performances of space geodesy missions. In this context, CNES initiated an assessment study called GRICE (GRadiométrie à Interféromètres quantiques Corrélés pour l'Espace) in order to evaluate the contribution of cold atom technologies to space geodesy and to the end users of geodetic data. In this paper, we present mission scenario for gravity field mapping based on a long baseline gradiometer. The mission is based on a constellation of two satellites, flying at an altitude of 373 km, each equipped with a cold atom accelerometer with a sensitivity of \\(6 10^-10\\)~m.s\\(^-2\\).\\(^-1/2\\). A laser link measures the distance between the two satellites and couples these two instruments in order to produce a correlated differential acceleration measurement. The main parameters, determining the performances of the payload, have been investigated. We carried out a general study of satellite architecture and simulations of the mission performances in terms of restitution of the gravity field. The simulations show that this concept would give its best performance in terms of monthly gravity fields recovery under 1000~km resolution. In the resolution band between 1000 and 222~km, the improvement of the GRICE gradient approach over the traditional range-rate approach is globally in the order of 10 to 25\\%.

The first line of defence The inflammasome is a complex of proteins involved in the activation of the innate immune system, an evolutionarily ancient antimicrobial defence found in most multicelled animals. When activated the inflammasome sets in motion a cascade of events that leads to the production of active molecules including interleukins. Three papers in this issue report the identification of endogenous danger signals and bacterial components that activate inflammasomes containing cryopyrin (also known as NALP3). Mariathasan et al . show that cryopyrin activates the inflammasome in response to bacterial toxins and to ATP. Kanneganti et al . show that cryopyrin is activated by bacterial RNA and by the immune response modifiers R837 and R848. And Martinon et al . show that gout-associated uric acid crystals have a similar effect. In sum these results show that cryopyrin has a vital role in host antibacterial defences and may act as a sensor of cellular stress. In addition, this work provides insight into the mechanisms of autoinflammatory disorders in which abnormalities in the innate immune system have been implicated. Development of the acute and chronic inflammatory responses known as gout and pseudogout are associated with the deposition of monosodium urate (MSU) or calcium pyrophosphate dihydrate (CPPD) crystals, respectively, in joints and periarticular tissues. Although MSU crystals were first identified as the aetiological agent of gout in the eighteenth century 1 and more recently as a ‘danger signal’ released from dying cells 2 , little is known about the molecular mechanisms underlying MSU- or CPPD-induced inflammation. Here we show that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1β and IL-18. Macrophages from mice deficient in various components of the inflammasome such as caspase-1, ASC and NALP3 are defective in crystal-induced IL-1β activation. Moreover, an impaired neutrophil influx is found in an in vivo model of crystal-induced peritonitis in inflammasome-deficient mice or mice deficient in the IL-1β receptor (IL-1R). These findings provide insight into the molecular processes underlying the inflammatory conditions of gout and pseudogout, and further support a pivotal role of the inflammasome in several autoinflammatory diseases.

Highly parallel SNP genotyping platforms have been developed for some important crop species, but these platforms typically carry a high cost per sample for first-time or small-scale users. In contrast, recently developed genotyping by sequencing (GBS) approaches offer a highly cost effective alternative for simultaneous SNP discovery and genotyping. In the present investigation, we have explored the use of GBS in soybean. In addition to developing a novel analysis pipeline to call SNPs and indels from the resulting sequence reads, we have devised a modified library preparation protocol to alter the degree of complexity reduction. We used a set of eight diverse soybean genotypes to conduct a pilot scale test of the protocol and pipeline. Using ApeKI for GBS library preparation and sequencing on an Illumina GAIIx machine, we obtained 5.5 M reads and these were processed using our pipeline. A total of 10,120 high quality SNPs were obtained and the distribution of these SNPs mirrored closely the distribution of gene-rich regions in the soybean genome. A total of 39.5% of the SNPs were present in genic regions and 52.5% of these were located in the coding sequence. Validation of over 400 genotypes at a set of randomly selected SNPs using Sanger sequencing showed a 98% success rate. We then explored the use of selective primers to achieve a greater complexity reduction during GBS library preparation. The number of SNP calls could be increased by almost 40% and their depth of coverage was more than doubled, thus opening the door to an increase in the throughput and a significant decrease in the per sample cost. The approach to obtain high quality SNPs developed here will be helpful for marker assisted genomics as well as assessment of available genetic resources for effective utilisation in a wide number of species.

The signaling intermediates that activate inflammasomes have remained elusive. Tschopp and co-workers now describe that a thioredoxin-binding protein is a reactive oxygen species–regulated component of the NLRP3 inflammasome. The NLRP3 inflammasome has a major role in regulating innate immunity. Deregulated inflammasome activity is associated with several inflammatory diseases, yet little is known about the signaling pathways that lead to its activation. Here we show that NLRP3 interacted with thioredoxin (TRX)-interacting protein (TXNIP), a protein linked to insulin resistance. Inflammasome activators such as uric acid crystals induced the dissociation of TXNIP from thioredoxin in a reactive oxygen species (ROS)-sensitive manner and allowed it to bind NLRP3. TXNIP deficiency impaired activation of the NLRP3 inflammasome and subsequent secretion of interleukin 1β (IL-1β). Akin to Txnip −/− mice, Nlrp3 −/− mice showed improved glucose tolerance and insulin sensitivity. The participation of TXNIP in the NLRP3 inflammasome activation may provide a mechanistic link to the observed involvement of IL-1β in the pathogenesis of type 2 diabetes.

Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1β is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1β secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1β in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1α, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with α-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1β by microglia, despite a weak pro-inflammatory effect. Amyloid-β peptides were able to activate the NLRP3 inflammasome in microglia and IL-1β secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions.