The cirrhotic liver is depleted of docosahexaenoic acid (DHA), a key modulator of NF-κB and TGFβ pathways in hepatic stellate cells

Liver cirrhosis results from chronic hepatic damage and is characterized by derangement of the organ architecture with increased liver fibrogenesis and defective hepatocellular function. It frequently evolves into progressive hepatic insufficiency associated with high mortality unless liver transplantation is performed. We have hypothesized that the deficiency of critical nutrients such as essential omega-3 fatty acids might play a role in the progression of liver cirrhosis. Here we evaluated by LC-MS/MS the liver content of omega-3 docosahexaenoic fatty acid (DHA) in cirrhotic patients and investigated the effect of DHA in a murine model of liver injury and in the response of hepatic stellate cells (HSCs) (the main producers of collagen in the liver) to pro-fibrogenic stimuli. We found that cirrhotic livers exhibit a marked depletion of DHA and that this alteration correlates with the progression of the disease. Administration of DHA exerts potent anti-fibrogenic effects in an acute model of liver damage. Studies with HSCs show that DHA inhibits fibrogenesis more intensely than other omega-3 fatty acids. Data from expression arrays revealed that DHA blocks TGFβ and NF-κB pathways. Mechanistically, DHA decreases late, but not early, SMAD3 nuclear accumulation and inhibits p65/RelA-S536 phosphorylation, which is required for HSC survival. Notably, DHA increases ADRP expression, leading to the formation of typical quiescence-associated perinuclear lipid droplets. In conclusion, a marked depletion of DHA is present in the liver of patients with advanced cirrhosis. DHA displays anti-fibrogenic activities on HSCs targeting NF-κB and TGFβ pathways and inducing ADPR expression and quiescence in these cells

Superconductivity in Weyl Semimetal Candidate MoTe2

In recent years, layered transition-metal dichalcogenides (TMDs) have attracted considerable attention because of their rich physics; for example, these materials exhibit superconductivity, charge density waves, and the valley Hall effect. As a result, TMDs have promising potential applications in electronics, catalysis, and spintronics. Despite the fact that the majority of related research focuses on semiconducting TMDs (e.g., MoS2), the characteristics of WTe2 are provoking strong interest in semimetallic TMDs with extremely large magnetoresistance, pressure-driven superconductivity, and the predicted Weyl semimetal (WSM) state. In this work, we investigate the sister compound of WTe2, MoTe2, which is also predicted to be a WSM and a quantum spin Hall insulator in bulk and monolayer form, respectively. We find that MoTe2 exhibits superconductivity with a resistive transition temperature Tc of 0.1 K. The application of a small pressure (such as 0.4 GPa) is shown to dramatically enhance the Tc, with a maximum value of 8.2 K being obtained at 11.7 GPa (a more than 80-fold increase in Tc). This yields a dome-shaped superconducting phase diagram. Further explorations into the nature of the superconductivity in this system may provide insights into the interplay between strong correlations and topological physics.Comment: 20 pages, 5 figure

Determination of the lunar body tide from global laser altimetry data

We use global data from the Lunar Orbiter Laser Altimeter (LOLA) to retrieve the lunar tidal Love number h2 and find h2 = 0.0387 ± 0.0025. This result is in agreement with previous estimates from laser altimetry using crossover points of LOLA profiles. The Love numbers k2 and h2 are key constraints on planetary interior models. We further develop and apply a retrieval method based on a simultaneous inversion for the topography and the tidal signal benefiting from the large volume of LOLA data. By the application to the lunar tides, we also demonstrate the potential of the method for future altimetry experiments at other planetary bodies. The results of this study are very promising with respect to the determination of Mercury’s and Ganymede’s h2 from future altimeter measurements.DLR Space AdministrationInternational Max Planck Research School on Solar System Science at the University of GöttingenDeutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/50110000165

Determination of the lunar body tide from global laser altimetry data

We use global data from the Lunar Orbiter Laser Altimeter (LOLA) to retrieve the lunar tidal Love number h2 and find h2=0.0387±0.0025. This result is in agreement with previous estimates from laser altimetry using crossover points of LOLA profiles. The Love numbers k2 and h2 are key constraints on planetary interior models. We further develop and apply a retrieval method based on a simultaneous inversion for the topography and the tidal signal benefiting from the large volume of LOLA data. By the application to the lunar tides, we also demonstrate the potential of the method for future altimetry experiments at other planetary bodies. The results of this study are very promising with respect to the determination of Mercury’s and Ganymede’s h2 from future altimeter measurements.TU Berlin, Open-Access-Mittel – 202

The cirrhotic liver is depleted of docosahexaenoic acid (DHA), a key modulator of NF-κB and TGFβ pathways in hepatic stellate cells

Liver cirrhosis results from chronic hepatic damage and is characterized by derangement of the organ architecture with increased liver fibrogenesis and defective hepatocellular function. It frequently evolves into progressive hepatic insufficiency associated with high mortality unless liver transplantation is performed. We have hypothesized that the deficiency of critical nutrients such as essential omega-3 fatty acids might play a role in the progression of liver cirrhosis. Here we evaluated by LC-MS/MS the liver content of omega-3 docosahexaenoic fatty acid (DHA) in cirrhotic patients and investigated the effect of DHA in a murine model of liver injury and in the response of hepatic stellate cells (HSCs) (the main producers of collagen in the liver) to pro-fibrogenic stimuli. We found that cirrhotic livers exhibit a marked depletion of DHA and that this alteration correlates with the progression of the disease. Administration of DHA exerts potent anti-fibrogenic effects in an acute model of liver damage. Studies with HSCs show that DHA inhibits fibrogenesis more intensely than other omega-3 fatty acids. Data from expression arrays revealed that DHA blocks TGFβ and NF-κB pathways. Mechanistically, DHA decreases late, but not early, SMAD3 nuclear accumulation and inhibits p65/RelA-S536 phosphorylation, which is required for HSC survival. Notably, DHA increases ADRP expression, leading to the formation of typical quiescence-associated perinuclear lipid droplets. In conclusion, a marked depletion of DHA is present in the liver of patients with advanced cirrhosis. DHA displays anti-fibrogenic activities on HSCs targeting NF-κB and TGFβ pathways and inducing ADPR expression and quiescence in these cells

N012 Endovascular gingival fibroblast cell therapy reduced the size of aneurysms in a rabbit model of elastase-induced carotid injury

BackgroundAortic abdominal aneurysm is characterized by excessive enlargement remodeling secondary to medial elastin destruction, and the severity of the disease has been correlated with metalloproteinase-9 (MMP-9). We aimed to evaluate whether embryo-like healing potential of a tissue (i.e., the gum) could be transposed to another tissue (i.e., the artery wall).Methods and ResultsPorcine pancreatic elastase was incubated during 15minutes in rabbit carotid arteries (n=30). Four to 6 weeks later, carotid arteries were seeded endoluminally at the site of aneurysm with either rabbit gingival fibroblasts (n=12) or culture medium only which served as control (n=11). Vessel diameter and elastin density were assessed 4 weeks after cell therapy. Carotid diameter was similar before cell therapy in both group (3.4±0.5mm vs 3.1±0.37mm, p=0.30). In contrast, carotid diameters were significantly decreased in aneurismal arteries seeded with rabbit gingival fibroblasts as compared to control aneurismal arteries (2.7±0.64mm vs 3.60±0.52, p=0.003). Moreover, elastin density was significantly higher in the media after endovascular gingival fibroblast than in controls (32.5±4.7 % vs 14.3±8.2 %, p=0.001). Four weeks after cell transplantation, gingival fibroblasts inhibited MMP-9 secretion via a significant increase of its inhibitor, TIMP-1.ConclusionsEndovascular gingival fibroblast cell therapy improved elastin network and reduced the size of aneurysms in a rabbit model. This strategy may be attractive since gingival fibroblast are easily accessible are known to safely proliferate in culture medium

Femoral arterial thrombosis after cardiac catheterization in infancy: impact of Doppler ultrasound for diagnosis

Femoral arterial thrombosis (FAT) is a nonnegligible complication after cardiac catheterization (CC) in infancy. The aim of this study was to evaluate the impact of Doppler ultrasound (US) for diagnostic work-up after catheterization. We compared standard follow-up (FU) without Doppler US by relying on clinical signs of FAT with advanced FU using Doppler US of the femoral vessels. Between January and December 2009, we evaluated the rate of FAT in infants <12 months of age using a multicenter, prospective observational survey. We analysed 171 patients [mean age 4.1 ± 3.3 (SD) months; mean body weight 5.3 ± 1.8 kg] from 6 participating centres. The mean duration of catheter studies was 57.7 ± 38.0 min. The overall rate of FAT based on clinical diagnosis was 4.7% and was comparable in both groups [3.4% undergoing standard FU vs. 7.4% undergoing advanced FU (p = 0.15)]. However, the overall rate of thrombosis as screened by Doppler US was greater at 7.1 %, especially in patients after advanced FU [18.5% advanced vs. standard FU 1.7% (p < 0.01)]. In conclusion, FAT remains a relevant and underestimated complication after catheterization in young infants when relying only on clinical signs of FAT. Therefore, to start effective treatment as soon as possible, we recommend Doppler US to be performed the day after CC

Prospects for measuring Mercury’s tidal Love number h2 with the BepiColombo Laser Altimeter

Context. The Love number h2 describes the radial tidal displacements of Mercury’s surface and allows constraints to be set on the inner core size when combined with the potential Love number k2. Knowledge of Mercury’s inner core size is fundamental to gaining insights into the planet’s thermal evolution and dynamo working principle. The BepiColombo Laser Altimeter (BELA) is currently cruising to Mercury as part of the BepiColombo mission and once it is in orbit around Mercury, it will acquire precise measurements of the planet’s surface topography, potentially including variability that is due to tidal deformation. Aims. We use synthetic measurements acquired using BELA to assess how accurately Mercury’s tidal Love number h2 can be determined by laser altimetry. Methods. We generated realistic, synthetic BELA measurements, including instrument performance, orbit determination, as well as uncertainties in spacecraft attitude and Mercury’s libration. We then retrieved Mercury’s h2 and global topography from the synthetic data through a joint inversion. Results. Our results suggest that h2 can be determined with an absolute accuracy of ± 0.012, enabling a determination of Mercury’s inner core size to ± 150 km given the inner core is sufficiently large (>800 km). We also show that the uncertainty of h2 depends strongly on the assumed scaling behavior of the topography at small scales and on the periodic misalignment of the instrument

The Ganymede Laser Altimeter (GALA)

The Ganymede Laser Altimeter (GALA) is one of the instruments selected for the first ESA large class mission JUICE. The scientific goals of the GALA instrument cover a wide range of questions of geology, geophysics and geodesy. Here we will present an overview on the scientific goals as well as on the instrument baseline design concept and the current performance analysis